Clinical chorioamnionitis at term IV: The maternal plasma cytokine profile

Journal of Perinatal Medicine

Volumn 44, Issue 1, 2016, Pages 77-98

  Romero, Roberto ^a,b,c,d   Chaemsaithong, Piya ^a,e   Docheva, Nikolina ^a,e   Korzeniewski, Steven J ^a,c,e   Tarca, Adi L ^a,e   Bhatti, Gaurav ^a,e   Xu, Zhonghui ^a,e   Kusanovic, Juan P ^a,f,g   Dong, Zhong ^a,e   Chaiyasit, Noppadol ^a,e   Ahmed, Ahmed I ^a,e   Yoon, Bo Hyun ^a,h   Hassan, Sonia S ^a,e   Chaiworapongsa, Tinnakorn ^a,e   Yeo, Lami ^a,e  

^a EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^c MICHIGAN STATE UNIVERSITY   (United States)

^d WAYNE STATE UNIVERSITY   (United States)

^e WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f HOSPITAL DR SÓTERO DEL RÍO   (Chile)

^g PONTIFICIA UNIVERSIDAD CATÓLICA DE CHILE   (Chile)

^h Seoul National University   (South Korea)

Author keywords

Acute histologic chorioamnionitis; amniotic fluid; biomarkers; chemokines; fever; funisitis; interferon gamma (IFN ); interleukin 1 (IL 1 ); interleukin 2 (IL 2); interleukin 6 (IL 6); microbial associated intra amniotic inflammation; pyrogens; tumor necrosis factor (TNF ); V PLEX immunoassays

Indexed keywords

CHEMOKINE; CYTOKINE; EOTAXIN; EOTAXIN 3; GAMMA INTERFERON; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 15; INTERLEUKIN 17ALPHA; INTERLEUKIN 2; INTERLEUKIN 5; INTERLEUKIN 6; MONOCYTE CHEMOTACTIC PROTEIN 4; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ADULT; AMNION FLUID ANALYSIS; AMNION FLUID LEVEL; ARTICLE; BACTERIUM DETECTION; CHORIOAMNIONITIS; CLINICAL ARTICLE; CLINICAL FEATURE; COMPARATIVE STUDY; CONTROLLED STUDY; CROSS-SECTIONAL STUDY; DISEASE CLASSIFICATION; FEMALE; FEVER; HUMAN; INFLAMMATION; LABOR; MATERNAL AGE; MATERNAL PLASMA; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BLOOD LEVEL; RETROSPECTIVE STUDY; YOUNG ADULT; AMNION FLUID; BLOOD; CASE CONTROL STUDY; IMMUNOLOGY; MICROBIOLOGY; NEWBORN; PREGNANCY; TERM BIRTH;

ADULT; AMNIOTIC FLUID; CASE-CONTROL STUDIES; CHEMOKINES; CHORIOAMNIONITIS; CROSS-SECTIONAL STUDIES; CYTOKINES; FEMALE; HUMANS; INFANT, NEWBORN; PREGNANCY; RETROSPECTIVE STUDIES; TERM BIRTH; YOUNG ADULT;

EID: 84955240198     PISSN: 03005577     EISSN: 16193997     Source Type: Journal    
DOI: 10.1515/jpm-2015-0103     Document Type: Article

References (357)

1. Gibbs RS. Diagnosis of intra-Amniotic infection. Semin Perinatol. 1977;1:71-7.
2. Gibbs RS, Castillo MS, Rodgers PJ. Management of acute chorioamnionitis. Am J Obstet Gynecol. 1980;136:709-13.
3. Gibbs RS, Blanco JD, St Clair PJ, Castaneda YS. Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term. J Infect Dis. 1982;145:1-8.
4. Romero R, Chaemsaithong P, Korzeniewski SJ, et al. Clinical chorioamnionitis at term III: how well do clinical criteria perform in the identification of proven intra-Amniotic infection?. J Perinat Med. 2016;44:23-32.
5. MacVicar J. Chorioamnionitis. Clin Obstet Gynecol. 1970;13:272-90.
6. Hollander D. Diagnosis of chorioamnionitis. Clin Obstet Gynecol. 1986;29:816-25.
7. Newton ER. Chorioamnionitis and intraamniotic infection. Clin Obstet Gynecol. 1993;36:795-808.
8. Tita AT, Andrews WW. Diagnosis and management of clinical chorioamnionitis. Clin Perinatol. 2010;37:339-54.
9. Romero R, Miranda J, Kusanovic JP, Chaiworapongsa T, Chaemsaithong P, Martinez A, et al. Clinical chorioamnionitis at term I: microbiology of the amniotic cavity using cultivation and molecular techniques. J Perinat Med. 2015;43:19-36.
10. Romero R, Chaiworapongsa T, Savasan ZA, Hussein Y, Dong Z, Kusanovic JP, et al. Clinical chorioamnionitis is characterized by changes in the expression of the alarmin HMGB1 and one of its receptors, sRAGE. J Matern Fetal Neonatal Med. 2012;25:558-67.
11. Fishman SG, Gelber SE. Evidence for the clinical management of chorioamnionitis. Semin Fetal Neonatal Med. 2012;17:46-50.
12. Romero R, Chaemsaithong P, Korzeniewski SJ, et al. Clinical chorioamnionitis at term II: the intra-Amniotic inflammatory response. J Perinat Med. 2016;44:5-22.
13. Romero R, Dey SK, Fisher SJ. Preterm labor: one syndrome, many causes. Science. 2014;345:760-5.
14. Duff P, Sanders R, Gibbs RS. The course of labor in term patients with chorioamnionitis. Am J Obstet Gynecol. 1983;147:391-5.
15. Hauth JC, Gilstrap LC 3rd, Hankins GD, Connor KD. Term maternal and neonatal complications of acute chorioamnionitis. Obstet Gynecol. 1985;66:59-62.
16. Satin AJ, Maberry MC, Leveno KJ, Sherman ML, Kline DM. Chorioamnionitis: a harbinger of dystocia. Obstet Gynecol. 1992;79:913-5.
17. Mark SP, Croughan-Minihane MS, Kilpatrick SJ. Chorioamnionitis and uterine function. Obstet Gynecol. 2000;95:909-12.
18. Rouse DJ, Landon M, Leveno KJ, Leindecker S, Varner MW, Caritis SN, et al. The maternal-fetal medicine units cesarean registry: chorioamnionitis at term and its duration-relationship to outcomes. Am J Obstet Gynecol. 2004;191:211-6.
19. Edwards RK. Chorioamnionitis and labor. Obstet Gynecol Clin North Am. 2005;32:287-96.
20. Yoder PR, Gibbs RS, Blanco JD, Castaneda YS, St Clair PJ. A prospective, controlled study of maternal and perinatal outcome after intra-Amniotic infection at term. Am J Obstet Gynecol. 1983;145:695-701.
21. Yancey MK, Duff P, Kubilis P, Clark P, Frentzen BH. Risk factors for neonatal sepsis. Obstet Gynecol. 1996;87:188-94.
22. Grether JK, Nelson KB. Maternal infection and cerebral palsy in infants of normal birth weight. J Am Med Assoc. 1997;278:207-11.
23. Ladfors L, Tessin I, Mattsson LA, Eriksson M, Seeberg S, Fall O. Risk factors for neonatal sepsis in offspring of women with prelabor rupture of the membranes at 34-42 weeks. J Perinat Med. 1998;26:94-101.
24. Alexander JM, McIntire DM, Leveno KJ. Chorioamnionitis and the prognosis for term infants. Obstet Gynecol. 1999;94:274-8.
25. Wu YW, Colford Jr. J.M. Chorioamnionitis as a risk factor for cerebral palsy: a meta-Analysis. J Am Med Assoc. 2000;284:1417-24.
26. Nelson KB, Willoughby RE. Infection, inflammation and the risk of cerebral palsy. Curr Opin Neurol. 2000;13:133-9.
27. Chaiworapongsa T, Romero R, Kim JC, Kim YM, Blackwell SC, Yoon BH, et al. Evidence for fetal involvement in the pathologic process of clinical chorioamnionitis. Am J Obstet Gynecol. 2002;186:1178-82.
28. Hagberg H, Wennerholm UB, Savman K. Sequelae of chorioamnionitis. Curr Opin Infect Dis. 2002;15:301-6.
29. Willoughby RE Jr, Nelson KB. Chorioamnionitis and brain injury. Clin Perinatol. 2002;29:603-21.
30. Wu YW, Escobar GJ, Grether JK, Croen LA, Greene JD, Newman TB. Chorioamnionitis and cerebral palsy in term and near-Term infants. J Am Med Assoc. 2003;290:2677-84.
31. Cooke R. Chorioamnionitis, maternal fever, and neonatal encephalopathy. Dev Med Child Neurol. 2008;50:9.
32. Blume HK, Li CI, Loch CM, Koepsell TD. Intrapartum fever and chorioamnionitis as risks for encephalopathy in term newborns: a case-control study. Dev Med Child Neurol. 2008;50:19-24.
33. Soraisham AS, Singhal N, McMillan DD, Sauve RS, Lee SK, Canadian Neonatal Network. A multicenter study on the clinical outcome of chorioamnionitis in preterm infants. Am J Obstet Gynecol. 2009;200:372.e1-6.
34. Shatrov JG, Birch SC, Lam LT, Quinlivan JA, McIntyre S, Mendz GL. Chorioamnionitis and cerebral palsy: a meta-Analysis. Obstet Gynecol. 2010;116:387-92.
35. Martinelli P, Sarno L, Maruotti GM, Paludetto R. Chorioamnionitis and prematurity: a critical review. J Matern Fetal Neonatal Med. 2012;25(Suppl 4):29-31.
36. de Sam Lazaro S, Cheng Y, Snowden J, Pereira L, Aziz N, Caughey A. Does the neonatal impact of chorioamnionitis in the setting of PPROM vary depending on degree of prematurity?. Am J Obstet Gynecol. 2013;208(Suppl):S314.
37. Garcia-Munoz Rodrigo F, Galan Henriquez GM, Ospina CG. Morbidity and mortality among very-low-birth-weight infants born to mothers with clinical chorioamnionitis. Pediatr Neonatol. 2014;55:381-6.
38. Uyemura A, Ameel B, Caughey A. Outcomes of chorioamnionitis in term pregnancies. Am J Obstet Gynecol. 2014;210(Suppl):S215.
39. Malloy MH. Chorioamnionitis: epidemiology of newborn management and outcome United States 2008. J Perinatol. 2014;34:611-5.
40. Mendez-Figueroa H, Abramovici A, O Neil AE, Dahlke J, Pedroza C, Chauhan S. Chorioamnionitis without and with neonatal sepsis: newborn and infant outcomes. Am J Obstet Gynecol. 2015;212(Suppl):S318-9.
41. Dinarello CA, Bunn Jr. P.A. Fever. Semin Oncol. 1997;24: 288-98.
42. Dinarello CA. Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed. J Endotoxin Res. 2004;10:201-22.
43. Conti B, Tabarean I, Andrei C, Bartfai T. Cytokines and fever. Front Biosci. 2004;9:1433-49.
44. Dinarello CA. Interleukin-1. Rev Infect Dis. 1984;6:51-95.
45. Sobrado J, Moldawer LL, Bistrian BR, Dinarello CA, Blackburn GL. Effect of ibuprofen on fever and metabolic changes induced by continuous infusion of leukocytic pyrogen (interleukin 1) or endotoxin. Infect Immun. 1983;42:997-1005.
46. Opp MR, Krueger JM. Interleukin 1-receptor antagonist blocks interleukin 1-induced sleep and fever. Am J Physiol. 1991;260:R453-7.
47. Luheshi G, Miller AJ, Brouwer S, Dascombe MJ, Rothwell NJ, Hopkins SJ. Interleukin-1 receptor antagonist inhibits endotoxin fever and systemic interleukin-6 induction in the rat. Am J Physiol. 1996;270:E91-5.
48. Gourine AV, Rudolph K, Tesfaigzi J, Kluger MJ. Role of hypothalamic interleukin-1beta in fever induced by cecal ligation and puncture in rats. Am J Physiol. 1998;275:R754-61.
49. Lundkvist J, Sundgren-Andersson AK, Tingsborg S, Ostlund P, Engfors C, Alheim K, et al. Acute-phase responses in transgenic mice with CNS overexpression of IL-1 receptor antagonist. Am J Physiol. 1999;276:R644-51.
50. Boneberg EM, Hartung T. Febrile temperatures attenuate IL-1 beta release by inhibiting proteolytic processing of the proform and influence Th1/Th2 balance by favoring Th2 cytokines. J Immunol. 2003;171:664-8.
51. Garlanda C, Dinarello CA, Mantovani A. The interleukin-1 family: back to the future. Immunity. 2013;39:1003-18.
52. Nedwin GE, Svedersky LP, Bringman TS, Palladino MA Jr, Goeddel DV. Effect of interleukin 2, interferon-gamma, and mitogens on the production of tumor necrosis factors alpha and beta. J Immunol. 1985;135:2492-7.
53. Lotze MT, Matory YL, Rayner AA, Ettinghausen SE, Vetto JT, Seipp CA, et al. Clinical effects and toxicity of interleukin-2 in patients with cancer. Cancer. 1986;58:2764-72.
54. Mier JW, Vachino G, van der Meer JW, Numerof RP, Adams S, Cannon JG, et al. Induction of circulating tumor necrosis factor (TNF alpha) as the mechanism for the febrile response to interleukin-2 (IL-2) in cancer patients. J Clin Immunol. 1988;8:426-36.
55. Ueno Y, Takano N, Kanegane H, Yokoi T, Yachie A, Miyawaki T, et al. The acute phase nature of interleukin 6: studies in Kawasaki disease and other febrile illnesses. Clin Exp Immunol. 1989;76:337-42.
56. LeMay LG, Vander AJ, Kluger MJ. Role of interleukin 6 in fever in rats. Am J Physiol. 1990;258:R798-803.
57. Coceani F, Lees J, Mancilla J, Belizario J, Dinarello CA. Interleukin-6 and tumor necrosis factor in cerebrospinal fluid: changes during pyrogen fever. Brain Res. 1993;612:165-71.
58. Chai Z, Gatti S, Toniatti C, Poli V, Bartfai T. Interleukin (IL)-6 gene expression in the central nervous system is necessary for fever response to lipopolysaccharide or IL-1 beta: a study on IL-6-Deficient mice. J Exp Med. 1996;183:311-6.
59. Cartmell T, Poole S, Turnbull AV, Rothwell NJ, Luheshi GN. Circulating interleukin-6 mediates the febrile response to localised inflammation in rats. J Physiol. 2000;526:653-61.
60. Dinarello CA, Bernheim HA, Duff GW, Le HV, Nagabhushan TL, Hamilton NC, et al. Mechanisms of fever induced by recombinant human interferon. J Clin Invest. 1984;74:906-13.
61. Luheshi GN. Cytokines and fever. Mechanisms and sites of action. Ann NY Acad Sci. 1998;856:83-9.
62. Dinarello CA, Cannon JG, Wolff SM, Bernheim HA, Beutler B, Cerami A, et al. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med. 1986;163:1433-50.
63. Nakamura H, Seto Y, Motoyoshi S, Kadokawa T, Sunahara N. Recombinant human tumor necrosis factor causes long-lasting and prostaglandin-mediated fever, with little tolerance, in rabbits. J Pharmacol Exp Ther. 1988;245:336-41.
64. Morimoto A, Sakata Y, Watanabe T, Murakami N. Characteristics of fever and acute-phase response induced in rabbits by IL-1 and TNF. Am J Physiol. 1989;256:R35-41.
65. Kawasaki H, Moriyama M, Ohtani Y, Naitoh M, Tanaka A, Nariuchi H. Analysis of endotoxin fever in rabbits by using a monoclonal antibody to tumor necrosis factor (cachectin). Infect Immun. 1989;57:3131-5.
66. Gay NJ, Keith FJ. Drosophila Toll and IL-1 receptor. Nature. 1991;351:355-6.
67. Dalpke A, Heeg K. Signal integration following Toll-like receptor triggering. Crit Rev Immunol. 2002;22:217-50.
68. Beutler B. Toll-like receptors: how they work and what they do. Curr Opin Hematol. 2002;9:2-10.
69. Leon LR. Invited review: cytokine regulation of fever: studies using gene knockout mice. J Appl Physiol (1985). 2002;92:2648-55.
70. Romanovsky AA, Almeida MC, Aronoff DM, Ivanov AI, Konsman JP, Steiner AA, et al. Fever and hypothermia in systemic inflammation: recent discoveries and revisions. Front Biosci. 2005;10:2193-216.
71. Li S, Wang Y, Matsumura K, Ballou LR, Morham SG, Blatteis CM. The febrile response to lipopolysaccharide is blocked in cyclooxygenase-2(-/-), but not in cyclooxygenase-1(-/-) mice. Brain Res. 1999;825:86-94.
72. Li S, Ballou LR, Morham SG, Blatteis CM. Cyclooxygenase-2 mediates the febrile response of mice to interleukin-1beta. Brain Res. 2001;910:163-73.
73. Blatteis CM, Li S, Li Z, Feleder C, Perlik V. Cytokines, PGE2 and endotoxic fever: a re-Assessment. Prostaglandins Other Lipid Mediat. 2005;76:1-18.
74. Mier JW, Souza LM, Allegretta M, Boone T, Bernheim HA, Dinarello CA. Dissimilarities between purified human interleukin-1 and recombinant human interleukin-2 in the induction of fever, brain prostaglandin, and acute-phase protein synthesis. J Biol Response Mod. 1985;4:35-45.
75. Dinarello CA, Cannon JG, Mancilla J, Bishai I, Lees J, Coceani F. Interleukin-6 as an endogenous pyrogen: induction of prostaglandin E2 in brain but not in peripheral blood mononuclear cells. Brain Res. 1991;562:199-206.
76. Ushikubi F, Segi E, Sugimoto Y, Murata T, Matsuoka T, Kobayashi T, et al. Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3. Nature. 1998;395:281-4.
77. Dinarello CA, Gatti S, Bartfai T. Fever: links with an ancient receptor. Curr Biol. 1999;9:R147-50.
78. Li S, Goorha S, Ballou LR, Blatteis CM. Intracerebroventricular interleukin-6, macrophage inflammatory protein-1 beta and IL-18: pyrogenic and PGE(2)-mediated?. Brain Res. 2003;992:76-84.
79. Ivanov AI, Romanovsky AA. Prostaglandin E2 as a mediator of fever: synthesis and catabolism. Front Biosci. 2004;9:1977-93.
80. Oka T. Prostaglandin E2 as a mediator of fever: the role of prostaglandin E (EP) receptors. Front Biosci. 2004;9:3046-57.
81. Laburn HP, Rosendorff C, Willies G, Woolf C. Proceedings: a role for noradrenaline and cyclic AMP in prostaglandin E1 Fever. J Physiol. 1974;240:49P-50P.
82. Hou CC, Lin H, Chang CP, Huang WT, Lin MT. Oxidative stress and pyrogenic fever pathogenesis. Eur J Pharmacol. 2011;667:6-12.
83. Lieberman E, Lang JM, Frigoletto F Jr, Richardson DK, Ringer SA, Cohen A. Epidural analgesia, intrapartum fever, and neonatal sepsis evaluation. Pediatrics. 1997;99:415-9.
84. Gonen R, Korobochka R, Degani S, Gaitini L. Association between epidural analgesia and intrapartum fever. Am J Perinatol. 2000;17:127-30.
85. Goetzl L, Cohen A, Frigoletto F Jr, Ringer SA, Lang JM, Lieberman E. Maternal epidural use and neonatal sepsis evaluation in afebrile mothers. Pediatrics. 2001;108:1099-102.
86. Yancey MK, Zhang J, Schwarz J, Dietrich CS 3rd, Klebanoff M. Labor epidural analgesia and intrapartum maternal hyperthermia. Obstet Gynecol. 2001;98:763-70.
87. Smulian JC, Bhandari V, Vintzileos AM, Shen-Schwarz S, Quashie C, Lai-Lin YL, et al. Intrapartum fever at term: serum and histologic markers of inflammation. Am J Obstet Gynecol. 2003;188:269-74.
88. Evron S, Parameswaran R, Zipori D, Ezri T, Sadan O, Koren R. Activin betaA in term placenta and its correlation with placental inflammation in parturients having epidural or systemic meperidine analgesia: a randomized study. J Clin Anesth. 2007;19:168-74.
89. Riley LE, Celi AC, Onderdonk AB, Roberts DJ, Johnson LC, Tsen LC, et al. Association of epidural-related fever and noninfectious inflammation in term labor. Obstet Gynecol. 2011;117:588-95.
90. Kovo M, Schreiber L, Ben-Haroush A, Shor S, Golan A, Bar J. Intrapartum fever at term: clinical characteristics and placental pathology. J Matern Fetal Neonatal Med. 2012;25:1273-7.
91. Sharma SK, Rogers BB, Alexander JM, McIntire DD, Leveno KJ. A randomized trial of the effects of antibiotic prophylaxis on epidural-related fever in labor. Anesth Analg. 2014;118:604-10.
92. Gleeson NC, Nolan KM, Ford MR. Temperature, labour, and epidural analgesia. Lancet. 1989;2:861-2.
93. Fusi L, Steer PJ, Maresh MJ, Beard RW. Maternal pyrexia associated with the use of epidural analgesia in labour. Lancet. 1989;1:1250-2.
94. Vinson DC, Thomas R, Kiser T. Association between epidural analgesia during labor and fever. J Fam Pract. 1993;36:617-22.
95. Ramin SM, Gambling DR, Lucas MJ, Sharma SK, Sidawi JE, Leveno KJ. Randomized trial of epidural versus intravenous analgesia during labor. Obstet Gynecol. 1995;86:783-9.
96. Mayer DC, Chescheir NC, Spielman FJ. Increased intrapartum antibiotic administration associated with epidural analgesia in labor. Am J Perinatol. 1997;14:83-6.
97. Sharma SK, Sidawi JE, Ramin SM, Lucas MJ, Leveno KJ, Cunningham FG. Cesarean delivery: a randomized trial of epidural versus patient-controlled meperidine analgesia during labor. Anesthesiology. 1997;87:487-94.
98. Dashe JS, Rogers BB, McIntire DD, Leveno KJ. Epidural analgesia and intrapartum fever: placental findings. Obstet Gynecol. 1999;93:341-4.
99. Philip J, Alexander JM, Sharma SK, Leveno KJ, McIntire DD, Wiley J. Epidural analgesia during labor and maternal fever. Anesthesiology. 1999;90:1271-5.
100. Lucas MJ, Sharma SK, McIntire DD, Wiley J, Sidawi JE, Ramin SM, et al. A randomized trial of labor analgesia in women with pregnancy-induced hypertension. Am J Obstet Gynecol. 2001;185:970-5.
101. Sharma SK, Alexander JM, Messick G, Bloom SL, McIntire DD, Wiley J, et al. Cesarean delivery: a randomized trial of epidural analgesia versus intravenous meperidine analgesia during labor in nulliparous women. Anesthesiology. 2002;96:546-51.
102. Goetzl L, Rivers J, Zighelboim I, Wali A, Badell M, Suresh MS. Intrapartum epidural analgesia and maternal temperature regulation. Obstet Gynecol. 2007;109:687-90.
103. Segal S. Labor epidural analgesia and maternal fever. Anesth Analg. 2010;111:1467-75.
104. Goetzl L. Epidural analgesia and maternal fever: a clinical and research update. Curr Opin Anaesthesiol. 2012;25:292-9.
105. Greenwell EA, Wyshak G, Ringer SA, Johnson LC, Rivkin MJ, Lieberman E. Intrapartum temperature elevation, epidural use, and adverse outcome in term infants. Pediatrics. 2012;129:e447-54.
106. Arendt KW, Segal BS. The association between epidural labor analgesia and maternal fever. Clin Perinatol. 2013;40:385-98.
107. Goetzl L. Epidural fever in obstetric patients: it s a hot topic. Anesth Analg. 2014;118:494-5.
108. DiGiulio DB, Romero R, Amogan HP, Kusanovic JP, Bik EM, Gotsch F, et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culturebased investigation. PLoS One. 2008;3:e3056.
109. DiGiulio DB, Romero R, Kusanovic JP, Gomez R, Kim CJ, Seok KS, et al. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol. 2010;64: 38-57.
110. DiGiulio DB, Gervasi M, Romero R, Mazaki-Tovi S, Vaisbuch E, Kusanovic JP, et al. Microbial invasion of the amniotic cavity in pre-Eclampsia as assessed by cultivation and sequencebased methods. J Perinat Med. 2010;38:503-13.
111. DiGiulio DB, Gervasi MT, Romero R, Vaisbuch E, Mazaki-Tovi S, Kusanovic JP, et al. Microbial invasion of the amniotic cavity in pregnancies with small-for-gestational-Age fetuses. J Perinat Med. 2010;38:495-502.
112. Yoon BH, Romero R, Moon JB, Shim SS, Kim M, Kim G, et al. Clinical significance of intra-Amniotic inflammation in patients with preterm labor and intact membranes. Am J Obstet Gynecol. 2001;185:1130-6.
113. Romero R, Chaiworapongsa T, Alpay Savasan Z, Xu Y, Hussein Y, Dong Z, et al. Damage-Associated molecular patterns (DAMPs) in preterm labor with intact membranes and preterm PROM: a study of the alarmin HMGB1. J Matern Fetal Neonatal Med. 2011;24:1444-55.
114. Gervasi MT, Romero R, Bracalente G, Erez O, Dong Z, Hassan SS, et al. Midtrimester amniotic fluid concentrations of interleukin-6 and interferon-gamma-inducible protein-10: evidence for heterogeneity of intra-Amniotic inflammation and associations with spontaneous early ( ?32 weeks) preterm delivery. J Perinat Med. 2012;40:329-43.
115. Kim SK, Romero R, Savasan ZA, Xu Y, Dong Z, Lee DC, et al. Endoglin in amniotic fluid as a risk factor for the subsequent development of bronchopulmonary dysplasia. Am J Reprod Immunol. 2013;69:105-23.
116. Romero R, Miranda J, Chaiworapongsa T, Chaemsaithong P, Gotsch F, Dong Z, et al. A novel molecular microbiologic technique for the rapid diagnosis of microbial invasion of the amniotic cavity and intra-Amniotic infection in preterm labor with intact membranes. Am J Reprod Immunol. 2014;71:330-58.
117. Romero R, Miranda J, Chaemsaithong P, Chaiworapongsa T, Kusanovic JP, Dong Z, et al. Sterile and microbial-Associated intra-Amniotic inflammation in preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2014;1-16. [Epub ahead of print].
118. Romero R, Miranda J, Chaiworapongsa T, Chaemsaithong P, Gotsch F, Dong Z, et al. Sterile intra-Amniotic inflammation in asymptomatic patients with a sonographic short cervix: prevalence and clinical significance. J Matern Fetal Neonatal Med. 2014;1-17. [Epub ahead of print].
119. Romero R, Miranda J, Chaiworapongsa T, Korzeniewski SJ, Chaemsaithong P, Gotsch F, et al. Prevalence and clinical significance of sterile intra-Amniotic inflammation in patients with preterm labor and intact membranes. Am J Reprod Immunol. 2014;72:458-74.
120. Chaemsaithong P, Romero R, Korzeniewski SJ, Dong Z, Yeo L, Hassan SS, et al. A point of care test for the determination of amniotic fluid interleukin-6 and the chemokine CXCL-10/IP-10. J Matern Fetal Neonatal Med. 2014;1-10. [Epub ahead of print].
121. Kacerovsky M, Musilova I, Andrys C, Hornychova H, Pliskova L, Kostal M, et al. Prelabor rupture of membranes between 34 and 37 weeks: the intraamniotic inflammatory response and neonatal outcomes. Am J Obstet Gynecol. 2014;210:325.e1-10.
122. Combs CA, Gravett M, Garite TJ, Hickok DE, Lapidus J, Porreco R, et al. Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol. 2014;210:125.e1-15.
123. Cobo T, Kacerovsky M, Jacobsson B. Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol. 2014;211:708.
124. Chaemsaithong P, Romero R, Korzeniewski SJ, Martinez-Varea A, Dong Z, Yoon BH, et al. A rapid interleukin-6 bedside test for the identification of intra-Amniotic inflammation in preterm labor with intact membranes. J Matern Fetal Neonatal Med. 2015;1-11. [Epub ahead of print].
125. Chaemsaithong P, Romero R, Korzeniewski SJ, Martinez-Varea A, Dong Z, Yoon BH, et al. A point of care test for interleukin-6 in amniotic fluid in preterm prelabor rupture of membrances: a step toward the early treatment of acute intra-Amniotic inflammation/infection. J Matern Fetal Neonatal Med. 2015;1-8. [Epub ahead of print].
126. Gibbs RS, Dinsmoor MJ, Newton ER, Ramamurthy RS. A randomized trial of intrapartum versus immediate postpartum treatment of women with intra-Amniotic infection. Obstet Gynecol. 1988;72:823-8.
127. Gilstrap LC 3rd, Cox SM. Acute chorioamnionitis. Obstet Gynecol Clin North Am. 1989;16:373-9.
128. Seeds JW. Impaired fetal growth: definition and clinical diagnosis. Obstet Gynecol. 1984;64:303-10.
129. Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United States national reference for fetal growth. Obstet Gynecol. 1996;87:163-8.
130. Redline RW, Heller D, Keating S, Kingdom J. Placental diagnostic criteria and clinical correlation-A workshop report. Placenta. 2005;26(Suppl A):S114-7.
131. Redline RW. Inflammatory responses in the placenta and umbilical cord. Semin Fetal Neonatal Med. 2006;11:296-301.
132. Chaiworapongsa T, Erez O, Kusanovic JP, Vaisbuch E, Mazaki-Tovi S, Gotsch F, et al. Amniotic fluid heat shock protein 70 concentration in histologic chorioamnionitis, term and preterm parturition. J Matern Fetal Neonatal Med. 2008;21:449-61.
133. Seong HS, Lee SE, Kang JH, Romero R, Yoon BH. The frequency of microbial invasion of the amniotic cavity and histologic chorioamnionitis in women at term with intact membranes in the presence or absence of labor. Am J Obstet Gynecol. 2008;199:375.e1-5.
134. Park CW, Moon KC, Park JS, Jun JK, Romero R, Yoon BH. The involvement of human amnion in histologic chorioamnionitis is an indicator that a fetal and an intra-Amniotic inflammatory response is more likely and severe: clinical implications. Placenta. 2009;30:56-61.
135. Kacerovsky M, Pliskova L, Bolehovska R, Musilova I, Hornychova H, Tambor V, et al. The microbial load with genital mycoplasmas correlates with the degree of histologic chorioamnionitis in preterm PROM. Am J Obstet Gynecol. 2011;205:213.e1-7.
136. Mi Lee S, Romero R, Lee KA, Jin Yang H, Joon Oh K, Park CW, et al. The frequency and risk factors of funisitis and histologic chorioamnionitis in pregnant women at term who delivered after the spontaneous onset of labor. J Matern Fetal Neonatal Med. 2011;24:37-42.
137. Tsiartas P, Kacerovsky M, Musilova I, Hornychova H, Cobo T, Savman K, et al. The association between histological chorioamnionitis, funisitis and neonatal outcome in women with preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2013;26:1332-6.
138. Korzeniewski SJ, Romero R, Cortez J, Pappas A, Schwartz AG, Kim CJ, et al. A "multi-hit" model of neonatal white matter injury: cumulative contributions of chronic placental inflammation, acute fetal inflammation and postnatal inflammatory events. J Perinat Med. 2014;42:731-43.
139. Kim SM, Romero R, Park JW, Oh KJ, Jun JK, Yoon BH. The relationship between the intensity of intra-Amniotic inflammation and the presence and severity of acute histologic chorioamnionitis in preterm gestation. J Matern Fetal Neonatal Med. 2014;1-10. doi:10.3109/14767058.2014.961009.
140. Pacora P, Chaiworapongsa T, Maymon E, Kim YM, Gomez R, Yoon BH, et al. Funisitis and chorionic vasculitis: the histological counterpart of the fetal inflammatory response syndrome. J Matern Fetal Neonatal Med. 2002;11:18-25.
141. Yoon BH, Romero R, Park JS, Kim M, Oh SY, Kim CJ, et al. The relationship among inflammatory lesions of the umbilical cord (funisitis), umbilical cord plasma interleukin 6 concentration, amniotic fluid infection, and neonatal sepsis. Am J Obstet Gynecol. 2000;183:1124-9.
142. Park JS, Romero R, Yoon BH, Moon JB, Oh SY, Han SY, et al. The relationship between amniotic fluid matrix metalloproteinase-8 and funisitis. Am J Obstet Gynecol. 2001;185:1156-61.
143. Yoon BH, Romero R, Shim JY, Shim SS, Kim CJ, Jun JK. C-reactive protein in umbilical cord blood: a simple and widely available clinical method to assess the risk of amniotic fluid infection and funisitis. J Matern Fetal Neonatal Med. 2003;14:85-90.
144. Lee SE, Romero R, Kim CJ, Shim SS, Yoon BH. Funisitis in term pregnancy is associated with microbial invasion of the amniotic cavity and intra-Amniotic inflammation. J Matern Fetal Neonatal Med. 2006;19:693-7.
145. Park CW, Lee SM, Park JS, Jun JK, Romero R, Yoon BH. The antenatal identification of funisitis with a rapid MMP-8 bedside test. J Perinat Med. 2008;36:497-502.
146. R Core Team. A language and environment for statistical computing. 2013. R Foundation for Statistical Computing, Vienna, Austria. http://www.R-project.org/. Accessed in January 2015.
147. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol. 1995;57:289-300.
148. Romero R, Mazor M, Wu YK, Sirtori M, Oyarzun E, Mitchell MD, et al. Infection in the pathogenesis of preterm labor. Semin Perinatol. 1988;12:262-79.
149. Romero R, Mazor M. Infection and preterm labor. Clin Obstet Gynecol. 1988;31:553-84.
150. Romero R, Sirtori M, Oyarzun E, Avila C, Mazor M, Callahan R, et al. Infection and labor. V. Prevalence, microbiology, and clinical significance of intraamniotic infection in women with preterm labor and intact membranes. Am J Obstet Gynecol. 1989;161:817-24.
151. Romero R, Avila C, Santhanam U, Sehgal PB. Amniotic fluid interleukin 6 in preterm labor. Association with infection. J Clin Invest. 1990;85:1392-400.
152. Romero R, Avila C, Brekus CA, Morotti R. The role of systemic and intrauterine infection in preterm parturition. Ann NY Acad Sci. 1991;622:355-75.
153. Gibbs RS, Romero R, Hillier SL, Eschenbach DA, Sweet RL. A review of premature birth and subclinical infection. Am J Obstet Gynecol. 1992;166:1515-28.
154. Gomez R, Romero R, Edwin SS, David C. Pathogenesis of preterm labor and preterm premature rupture of membranes associated with intraamniotic infection. Infect Dis Clin North Am. 1997;11:135-76.
155. Romero R, Gomez R, Chaiworapongsa T, Conoscenti G, Kim JC, Kim YM. The role of infection in preterm labour and delivery. Paediatr Perinat Epidemiol. 2001;15(Suppl 2):41-56.
156. Goncalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev. 2002;8:3-13.
157. Romero R, Espinoza J, Chaiworapongsa T, Kalache K. Infection and prematurity and the role of preventive strategies. Semin Neonatol. 2002;7:259-74.
158. Romero R, Espinoza J, Goncalves LF, Kusanovic JP, Friel LA, Nien JK. Inflammation in preterm and term labour and delivery. Semin Fetal Neonatal Med. 2006;11:317-26.
159. Romero R, Espinoza J, Kusanovic JP, Gotsch F, Hassan S, Erez O, et al. The preterm parturition syndrome. BJOG. 2006;113(Suppl 3):17-42.
160. Romero R, Gotsch F, Pineles B, Kusanovic JP. Inflammation in pregnancy: its roles in reproductive physiology, obstetrical complications, and fetal injury. Nutr Rev. 2007;65:S194-202.
161. Romero R, Lockwood CJ. Pathogenesis of spontaneous preterm labor. In: Creasy RK, Resnik R, Iams JD, Lockwood CJ, Moore TR, editors. Creasy and Resnik s maternal-fetal medicine: principles and practice. 6th ed. Philadelphia: Saunders Elsevier; 2009. pp. 545-82.
162. Bastek JA, Gomez LM, Elovitz MA. The role of inflammation and infection in preterm birth. Clin Perinatol. 2011;38: 385-406.
163. Agrawal V, Hirsch E. Intrauterine infection and preterm labor. Semin Fetal Neonatal Med. 2012;17:12-9.
164. Allen-Daniels MJ, Serrano MG, Pflugner LP, Fettweis JM, Prestosa MA, Koparde VN, et al. Identification of a gene in Mycoplasma hominis associated with preterm birth and microbial burden in intra-Amniotic infection. Am J Obstet Gynecol. 2015, [Epub ahead of print].
165. Zlatnik FJ, Cruikshank DP, Petzold CR, Galask RP. Amniocentesis in the identification of inapparent infection in preterm patients with premature rupture of the membranes. J Reprod Med. 1984;29:656-60.
166. Feinstein SJ, Vintzileos AM, Lodeiro JG, Campbell WA, Weinbaum PJ, Nochimson DJ. Amniocentesis with premature rupture of membranes. Obstet Gynecol. 1986;68:147-52.
167. Romero R, Quintero R, Oyarzun E, Wu YK, Sabo V, Mazor M, et al. Intraamniotic infection and the onset of labor in preterm premature rupture of the membranes. Am J Obstet Gynecol. 1988;159:661-6.
168. Mercer BM. Preterm premature rupture of the membranes. Obstet Gynecol. 2003;101:178-93.
169. Shim SS, Romero R, Hong JS, Park CW, Jun JK, Kim BI, et al. Clinical significance of intra-Amniotic inflammation in patients with preterm premature rupture of membranes. Am J Obstet Gynecol. 2004;191:1339-45.
170. Santolaya-Forgas J, Romero R, Espinoza J, Erez O, Friel LA, Kusanovic JP, et al. Prelabour rupture of the membranes. In: Reece EA, Hobbins JC, editors. Clinical obstetrics the fetus and mothers. 3rd ed. Malden: Blackwell; 2008. pp. 1130-88.
171. Romero R, Yeo L, Gotsch F, Soto E, Hassan S, Kusanovic JP, et al. Prelabor rupture of the membranes. In: Winn HN, Chervanak FA, Romero R, editors. Clinical maternal-fetal medicine online. 2nd ed. London: Informa Healthcare; 2011. pp. 1-24.
172. Kacerovsky M, Andrys C, Drahosova M, Musilova I, Hornychova H, Lesko D, et al. Soluble Toll-like receptor 1 family members in the amniotic fluid of women with preterm prelabor rupture of the membranes. J Matern Fetal Neonatal Med. 2012;25:1699-704.
173. Kacerovsky M, Musilova I, Khatibi A, Skogstrand K, Hougaard DM, Tambor V, et al. Intraamniotic inflammatory response to bacteria: analysis of multiple amniotic fluid proteins in women with preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2012;25:2014-9.
174. Ismail AQ, Lahiri S. Management of prelabour rupture of membranes (PROM) at term. J Perinat Med. 2013;41:647-9.
175. Eschenbach D. Reply to: Ismail AQT, Lahiri S. Management of prelabor rupture of membranes (PROM) at term J Perinat Med. 2013;41:653-5.
176. Grunebaum A. Reply to Management of prelabour rupture of membranes (PROM) at term . J Perinat Med. 2013;41:651-2.
177. Romero R, Gonzalez R, Sepulveda W, Brandt F, Ramirez M, Sorokin Y, et al. Infection and labor. VIII. Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: prevalence and clinical significance. Am J Obstet Gynecol. 1992;167:1086-91.
178. Lee SE, Romero R, Park CW, Jun JK, Yoon BH. The frequency and significance of intraamniotic inflammation in patients with cervical insufficiency. Am J Obstet Gynecol. 2008;198:633.e1-8.
179. Oh KJ, Lee SE, Jung H, Kim G, Romero R, Yoon BH. Detection of ureaplasmas by the polymerase chain reaction in the amniotic fluid of patients with cervical insufficiency. J Perinat Med. 2010;38:261-8.
180. Hassan SS, Romero R, Berry SM, Dang K, Blackwell SC, Treadwell MC, et al. Patients with an ultrasonographic cervical length or 15 mm have nearly a 50% risk of early spontaneous preterm delivery. Am J Obstet Gynecol. 2000 182 1458-67
181. Gomez R, Romero R, Nien JK, Chaiworapongsa T, Medina L, Kim YM, et al. A short cervix in women with preterm labor and intact membranes: a risk factor for microbial invasion of the amniotic cavity. Am J Obstet Gynecol. 2005;192:678-89.
182. Hassan S, Romero R, Hendler I, Gomez R, Khalek N, Espinoza J, et al. A sonographic short cervix as the only clinical manifestation of intra-Amniotic infection. J Perinat Med. 2006;34:13-9.
183. Kiefer DG, Keeler SM, Rust OA, Wayock CP, Vintzileos AM, Hanna N. Is midtrimester short cervix a sign of intraamniotic inflammation?. Am J Obstet Gynecol. 2009;200:374.e1-5.
184. Vaisbuch E, Hassan SS, Mazaki-Tovi S, Nhan-Chang CL, Kusanovic JP, Chaiworapongsa T, et al. Patients with an asymptomatic short cervix (
185. Vaisbuch E, Romero R, Erez O, Kusanovic JP, Mazaki-Tovi S, Gotsch F, et al. Clinical significance of early (
186. Elovitz MA, Wang Z, Chien EK, Rychlik DF, Phillippe M. A new model for inflammation-induced preterm birth: the role of platelet-Activating factor and Toll-like receptor-4. Am J Pathol. 2003;163:2103-11.
187. Wang H, Hirsch E. Bacterially-induced preterm labor and regulation of prostaglandin-metabolizing enzyme expression in mice: the role of toll-like receptor 4. Biol Reprod. 2003;69:1957-63.
188. Kim YM, Romero R, Chaiworapongsa T, Kim GJ, Kim MR, Kuivaniemi H, et al. Toll-like receptor-2 and-4 in the chorioamniotic membranes in spontaneous labor at term and in preterm parturition that are associated with chorioamnionitis. Am J Obstet Gynecol. 2004;191:1346-55.
189. Mor G, Romero R, Aldo PB, Abrahams VM. Is the trophoblast an immune regulator?. The role of Toll-like receptors during pregnancy. Crit Rev Immunol. 2005;25:375-88.
190. Koga K, Cardenas I, Aldo P, Abrahams VM, Peng B, Fill S, et al. Activation of TLR3 in the trophoblast is associated with preterm delivery. Am J Reprod Immunol. 2009;61:196-212.
191. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11:373-84.
192. Ilievski V, Hirsch E. Synergy between viral and bacterial toll-like receptors leads to amplification of inflammatory responses and preterm labor in the mouse. Biol Reprod. 2010;83:767-73.
193. Pawelczyk E, Nowicki BJ, Izban MG, Pratap S, Sashti NA, Sanderson M, et al. Spontaneous preterm labor is associated with an increase in the proinflammatory signal transducer TLR4 receptor on maternal blood monocytes. BMC Pregnancy Childbirth. 2010;10:66.
194. Li L, Kang J, Lei W. Role of Toll-like receptor 4 in inflammationinduced preterm delivery. Mol Hum Reprod. 2010;16:267-72.
195. Thaxton JE, Nevers TA, Sharma S. TLR-mediated preterm birth in response to pathogenic agents. Infect Dis Obstet Gynecol. 2010;2010:378472.
196. Breen K, Brown A, Burd I, Chai J, Friedman A, Elovitz MA. TLR-4-Dependent and-independent mechanisms of fetal brain injury in the setting of preterm birth. Reprod Sci. 2012;19:839-50.
197. Kacerovsky M, Andrys C, Hornychova H, Pliskova L, Lancz K, Musilova I, et al. Amniotic fluid soluble Toll-like receptor 4 in pregnancies complicated by preterm prelabor rupture of the membranes. J Matern Fetal Neonatal Med. 2012;25:1148-55.
198. Andrys C, Kacerovsky M, Drahosova M, Musilova I, Pliskova L, Hornychova H, et al. Amniotic fluid soluble Toll-like receptor 2 in pregnancies complicated by preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2013;26:520-7.
199. Abrahams VM, Potter JA, Bhat G, Peltier MR, Saade G, Menon R. Bacterial modulation of human fetal membrane Toll-like receptor expression. Am J Reprod Immunol. 2013;69:33-40.
200. Koga K, Izumi G, Mor G, Fujii T, Osuga Y. Toll-like receptors at the maternal-fetal interface in normal pregnancy and pregnancy complications. Am J Reprod Immunol. 2014;72:192-205.
201. Romero R, Durum SK, Dinarello CA. Interleukin-1: a signal for the initiation of labor in chorioamnionitis. 33rd Annual Meeting for the Society for Gynecologic Investigation. Toronto, Ontario; 1986.
202. Romero R, Brody DT, Oyarzun E, Mazor M, Wu YK, Hobbins JC, et al. Infection and labor. III. Interleukin-1: a signal for the onset of parturition. Am J Obstet Gynecol. 1989;160:1117-23.
203. Romero R, Manogue KR, Mitchell MD, Wu YK, Oyarzun E, Hobbins JC, et al. Infection and labor. IV. Cachectin-Tumor necrosis factor in the amniotic fluid of women with intraamniotic infection and preterm labor. Am J Obstet Gynecol. 1989;161:336-41.
204. Casey ML, Cox SM, Beutler B, Milewich L, MacDonald PC. Cachectin/tumor necrosis factor-Alpha formation in human decidua. Potential role of cytokines in infection-induced preterm labor. J Clin Invest. 1989;83:430-6.
205. Romero R, Parvizi ST, Oyarzun E, Mazor M, Wu YK, Avila C, et al. Amniotic fluid interleukin-1 in spontaneous labor at term. J Reprod Med. 1990;35:235-8.
206. Romero R, Mazor M, Brandt F, Sepulveda W, Avila C, Cotton DB, et al. Interleukin-1 alpha and interleukin-1 beta in preterm and term human parturition. Am J Reprod Immunol. 1992;27:117-23.
207. Romero R, Tartakovsky B. The natural interleukin-1 receptor antagonist prevents interleukin-1-induced preterm delivery in mice. Am J Obstet Gynecol. 1992;167:1041-5.
208. Romero R, Sepulveda W, Kenney JS, Archer LE, Allison AC, Sehgal PB. Interleukin 6 determination in the detection of microbial invasion of the amniotic cavity. Ciba Found Symp. 1992;167:205-20; discussion 220-3.
209. Romero R, Mazor M, Sepulveda W, Avila C, Copeland D, Williams J. Tumor necrosis factor in preterm and term labor. Am J Obstet Gynecol. 1992;166:1576-87.
210. Hillier SL, Witkin SS, Krohn MA, Watts DH, Kiviat NB, Eschenbach DA. The relationship of amniotic fluid cytokines and preterm delivery, amniotic fluid infection, histologic chorioamnionitis, and chorioamnion infection. Obstet Gynecol. 1993;81:941-8.
211. Romero R, Yoon BH, Kenney JS, Gomez R, Allison AC, Sehgal PB. Amniotic fluid interleukin-6 determinations are of diagnostic and prognostic value in preterm labor. Am J Reprod Immunol. 1993;30:167-83.
212. Romero R, Yoon BH, Mazor M, Gomez R, Diamond MP, Kenney JS, et al. The diagnostic and prognostic value of amniotic fluid white blood cell count, glucose, interleukin-6, and gram stain in patients with preterm labor and intact membranes. Am J Obstet Gynecol. 1993;169:805-16.
213. Saito S, Kasahara T, Kato Y, Ishihara Y, Ichijo M. Elevation of amniotic fluid interleukin 6 (IL-6), IL-8 and granulocyte colony stimulating factor (G-CSF) in term and preterm parturition. Cytokine. 1993;5:81-8.
214. Yoon BH, Romero R, Kim CJ, Jun JK, Gomez R, Choi JH, et al. Amniotic fluid interleukin-6: a sensitive test for antenatal diagnosis of acute inflammatory lesions of preterm placenta and prediction of perinatal morbidity. Am J Obstet Gynecol. 1995;172:960-70.
215. Arntzen KJ, Kjollesdal AM, Halgunset J, Vatten L, Austgulen R. TNF, IL-1, IL-6, IL-8 and soluble TNF receptors in relation to chorioamnionitis and premature labor. J Perinat Med. 1998;26:17-26.
216. Hsu CD, Meaddough E, Aversa K, Hong SF, Lu LC, Jones DC, et al. Elevated amniotic fluid levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 in intra-Amniotic infection. Am J Obstet Gynecol. 1998;179:1267-70.
217. Athayde N, Romero R, Maymon E, Gomez R, Pacora P, Yoon BH, et al. Interleukin 16 in pregnancy, parturition, rupture of fetal membranes, and microbial invasion of the amniotic cavity. Am J Obstet Gynecol. 2000;182:135-41.
218. Pacora P, Romero R, Maymon E, Gervasi MT, Gomez R, Edwin SS, et al. Participation of the novel cytokine interleukin 18 in the host response to intra-Amniotic infection. Am J Obstet Gynecol. 2000;183:1138-43.
219. Jacobsson B, Mattsby-Baltzer I, Hagberg H. Interleukin-6 and interleukin-8 in cervical and amniotic fluid: relationship to microbial invasion of the chorioamniotic membranes. BJOG. 2005;112:719-24.
220. Holst RM, Laurini R, Jacobsson B, Samuelsson E, Savman K, Doverhag C, et al. Expression of cytokines and chemokines in cervical and amniotic fluid: relationship to histological chorioamnionitis. J Matern Fetal Neonatal Med. 2007;20: 885-93.
221. Gotsch F, Romero R, Kusanovic JP, Erez O, Espinoza J, Kim CJ, et al. The anti-inflammatory limb of the immune response in preterm labor, intra-Amniotic infection/inflammation, and spontaneous parturition at term: a role for interleukin-10. J Matern Fetal Neonatal Med. 2008;21:529-47.
222. Marconi C, de Andrade Ramos BR, Peracoli JC, Donders GG, da Silva MG. Amniotic fluid interleukin-1 beta and interleukin-6, but not interleukin-8 correlate with microbial invasion of the amniotic cavity in preterm labor. Am J Reprod Immunol. 2011;65:549-56.
223. Kacerovsky M, Celec P, Vlkova B, Skogstrand K, Hougaard DM, Cobo T, et al. Amniotic fluid protein profiles of intraamniotic inflammatory response to Ureaplasma spp. and other bacteria. PLoS One. 2013;8:e60399.
224. Cobo T, Jacobsson B, Kacerovsky M, Hougaard DM, Skogstrand K, Gratacos E, et al. Systemic and local inflammatory response in women with preterm prelabor rupture of membranes. PLoS One. 2014;9:e85277.
225. Romero R, Ceska M, Avila C, Mazor M, Behnke E, Lindley I. Neutrophil attractant/activating peptide-1/interleukin-8 in term and preterm parturition. Am J Obstet Gynecol. 1991;165:813-20.
226. Cherouny PH, Pankuch GA, Romero R, Botti JJ, Kuhn DC, Demers LM, et al. Neutrophil attractant/activating peptide-1/ interleukin-8: association with histologic chorioamnionitis, preterm delivery, and bioactive amniotic fluid leukoattractants. Am J Obstet Gynecol. 1993;169:1299-303.
227. Puchner T, Egarter C, Wimmer C, Lederhilger F, Weichselbraun I. Amniotic fluid interleukin-8 as a marker for intraamniotic infection. Arch Gynecol Obstet. 1993;253:9-14.
228. Dudley DJ, Trautman MS, Mitchell MD. Inflammatory mediators regulate interleukin-8 production by cultured gestational tissues: evidence for a cytokine network at the chorio-Decidual interface. J Clin Endocrinol Metab. 1993;76:404-10.
229. Romero R, Gomez R, Galasso M, Munoz H, Acosta L, Yoon BH, et al. Macrophage inflammatory protein-1 alpha in term and preterm parturition: effect of microbial invasion of the amniotic cavity. Am J Reprod Immunol. 1994;32:108-13.
230. Dudley DJ, Spencer S, Edwin S, Mitchell MD. Regulation of human decidual cell macrophage inflammatory protein-1 alpha (MIP-1 alpha) production by inflammatory cytokines. Am J Reprod Immunol. 1995;34:231-5.
231. Cohen J, Ghezzi F, Romero R, Ghidini A, Mazor M, Tolosa JE, et al. GRO alpha in the fetomaternal and amniotic fluid compartments during pregnancy and parturition. Am J Reprod Immunol. 1996;35:23-9.
232. Dudley DJ, Hunter C, Mitchell MD, Varner MW. Elevations of amniotic fluid macrophage inflammatory protein-1 alpha concentrations in women during term and preterm labor. Obstet Gynecol. 1996;87:94-8.
233. Ghezzi F, Gomez R, Romero R, Yoon BH, Edwin SS, David C, et al. Elevated interleukin-8 concentrations in amniotic fluid of mothers whose neonates subsequently develop bronchopulmonary dysplasia. Eur J Obstet Gynecol Reprod Biol. 1998;78:5-10.
234. Hsu CD, Meaddough E, Aversa K, Copel JA. The role of amniotic fluid L-selectin, GRO-Alpha, and interleukin-8 in the pathogenesis of intraamniotic infection. Am J Obstet Gynecol. 1998;178:428-32.
235. Athayde N, Romero R, Maymon E, Gomez R, Pacora P, Araneda H, et al. A role for the novel cytokine RANTES in pregnancy and parturition. Am J Obstet Gynecol. 1999;181:989-94.
236. Jacobsson B, Holst RM, Wennerholm UB, Andersson B, Lilja H, Hagberg H. Monocyte chemotactic protein-1 in cervical and amniotic fluid: relationship to microbial invasion of the amniotic cavity, intra-Amniotic inflammation, and preterm delivery. Am J Obstet Gynecol. 2003;189:1161-7.
237. Keelan JA, Yang J, Romero RJ, Chaiworapongsa T, Marvin KW, Sato TA, et al. Epithelial cell-Derived neutrophil-Activating peptide-78 is present in fetal membranes and amniotic fluid at increased concentrations with intra-Amniotic infection and preterm delivery. Biol Reprod. 2004;70:253-9.
238. Chaiworapongsa T, Romero R, Espinoza J, Kim YM, Edwin S, Bujold E, et al. Macrophage migration inhibitory factor in patients with preterm parturition and microbial invasion of the amniotic cavity. J Matern Fetal Neonatal Med. 2005;18:405-16.
239. Esplin MS, Romero R, Chaiworapongsa T, Kim YM, Edwin S, Gomez R, et al. Monocyte chemotactic protein-1 is increased in the amniotic fluid of women who deliver preterm in the presence or absence of intra-Amniotic infection. J Matern Fetal Neonatal Med. 2005;17:365-73.
240. Holst RM, Mattsby-Baltzer I, Wennerholm UB, Hagberg H, Jacobsson B. Interleukin-6 and interleukin-8 in cervical fluid in a population of Swedish women in preterm labor: relationship to microbial invasion of the amniotic fluid, intra-Amniotic inflammation, and preterm delivery. Acta Obstet Gynecol Scand. 2005;84:551-7.
241. Hamill N, Romero R, Gotsch F, Kusanovic JP, Edwin S, Erez O, et al. Exodus-1 (CCL20): evidence for the participation of this chemokine in spontaneous labor at term, preterm labor, and intrauterine infection. J Perinat Med. 2008;36:217-27.
242. Cobo T, Kacerovsky M, Palacio M, Hornychova H, Hougaard DM, Skogstrand K, et al. A prediction model of histological chorioamnionitis and funisitis in preterm prelabor rupture of membranes: analyses of multiple proteins in the amniotic fluid. J Matern Fetal Neonatal Med. 2012;25:1995-2001.
243. Kacerovsky M, Musilova I, Jacobsson B, Drahosova M, Hornychova H, Janku P, et al. Cervical fluid IL-6 and IL-8 levels in pregnancies complicated by preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2015;28:134-40.
244. Kacerovsky M, Musilova I, Jacobsson B, Drahosova M, Hornychova H, Janku P, et al. Vaginal fluid IL-6 and IL-8 levels in pregnancies complicated by preterm prelabor membrane ruptures. J Matern Fetal Neonatal Med. 2015;28:392-8.
245. Romero R, Emamian M, Wan M, Quintero R, Hobbins JC, Mitchell MD. Prostaglandin concentrations in amniotic fluid of women with intra-Amniotic infection and preterm labor. Am J Obstet Gynecol. 1987;157:1461-7.
246. Romero R, Wu YK, Mazor M, Hobbins JC, Mitchell MD. Amniotic fluid prostaglandin E2 in preterm labor. Prostaglandins Leukot Essent Fatty Acids. 1988;34:141-5.
247. Romero R, Wu YK, Mazor M, Oyarzun E, Hobbins JC, Mitchell MD. Amniotic fluid arachidonate lipoxygenase metabolites in preterm labor. Prostaglandins Leukot Essent Fatty Acids. 1989;36:69-75.
248. Romero R, Mazor M, Wu YK, Avila C, Oyarzun E, Mitchell MD. Bacterial endotoxin and tumor necrosis factor stimulate prostaglandin production by human decidua. Prostaglandins Leukot Essent Fatty Acids. 1989;37:183-6.
249. Romero R, Wu YK, Hobbins JC, Mitchell MD. A monokine stimulates prostaglandin-E2 production by human amnion. Prostaglandins Leukot Essent Fatty Acids. 1990;41:67-9.
250. Mazor M, Wiznitzer A, Maymon E, Leiberman JR, Cohen A. Changes in amniotic fluid concentrations of prostaglandins E2 and F2 alpha in women with preterm labor. Isr J Med Sci. 1990;26:425-8.
251. Mitchell MD, Romero RJ, Avila C, Foster JT, Edwin SS. Prostaglandin production by amnion and decidual cells in response to bacterial products. Prostaglandins Leukot Essent Fatty Acids. 1991;42:167-9.
252. Mitchell MD, Romero RJ, Edwin SS, Trautman MS. Prostaglandins and parturition. Reprod Fertil Dev. 1995;7:623-32.
253. Hsu CD, Meaddough E, Aversa K, Hong SF, Lee IS, Bahodo-Singh RO, et al. Dual roles of amniotic fluid nitric oxide and prostaglandin E2 in preterm labor with intra-Amniotic infection. Am J Perinatol. 1998;15:683-7.
254. Mikamo H, Kawazoe K, Sato Y, Imai A, Tamaya T. Preterm labor and bacterial intraamniotic infection: arachidonic acid liberation by phospholipase A2 of Fusobacterium nucleatum. Am J Obstet Gynecol. 1998;179:1579-82.
255. Hertelendy F, Rastogi P, Molnar M, Romero R. Interleukin-1beta-induced prostaglandin E2 production in human myometrial cells: role of a pertussis toxin-sensitive component. Am J Reprod Immunol. 2001;45:142-7.
256. Hertelendy F, Molnar M, Romero R. Interferon gamma antagonizes interleukin-1beta-induced cyclooxygenase-2 expression and prostaglandin E(2) production in human myometrial cells. J Soc Gynecol Investig. 2002;9:215-9.
257. Mitchell MD, Chang MC, Chaiworapongsa T, Lan HY, Helliwell RJ, Romero R, et al. Identification of 9alpha,11betaprostaglandin F2 in human amniotic fluid and characterization of its production by human gestational tissues. J Clin Endocrinol Metab. 2005;90:4244-8.
258. Lee SE, Park IS, Romero R, Yoon BH. Amniotic fluid prostaglandin F2 increases even in sterile amniotic fluid and is an independent predictor of impending delivery in preterm premature rupture of membranes. J Matern Fetal Neonatal Med. 2009;22:880-6.
259. Maddipati KR, Romero R, Chaiworapongsa T, Zhou SL, Xu Z, Tarca AL, et al. Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor. FASEB J. 2014;28:4835-46.
260. Hong JS, Romero R, Lee DC, Than NG, Yeo L, Chaemsaithong P, et al. Umbilical cord prostaglandins in term and preterm parturition. J Matern Fetal Neonatal Med. 2015;1-9. [Epub ahead of print].
261. Park JY, Ahn TG, Lee J, Yoon BH. Elevated prostaglandin F2a concentration in amniotic fluid is an independent risk factor for intra-Amniotic inflammation and adverse pregnancy outcome in patients with preterm labor. Am J Obstet Gynecol. 2015;212:S360.
262. Athayde N, Romero R, Gomez R, Maymon E, Pacora P, Mazor M, et al. Matrix metalloproteinases-9 in preterm and term human parturition. J Matern Fetal Med. 1999;8:213-9.
263. Maymon E, Romero R, Pacora P, Gervasi MT, Bianco K, Ghezzi F, et al. Evidence for the participation of interstitial collagenase (matrix metalloproteinase 1) in preterm premature rupture of membranes. Am J Obstet Gynecol. 2000;183:914-20.
264. Maymon E, Romero R, Pacora P, Gervasi MT, Gomez R, Edwin SS, et al. Evidence of in vivo differential bioavailability of the active forms of matrix metalloproteinases 9 and 2 in parturition, spontaneous rupture of membranes, and intraamniotic infection. Am J Obstet Gynecol. 2000;183:887-94.
265. Maymon E, Romero R, Pacora P, Gomez R, Athayde N, Edwin S, et al. Human neutrophil collagenase (matrix metalloproteinase 8) in parturition, premature rupture of the membranes, and intrauterine infection. Am J Obstet Gynecol. 2000;183:94-9.
266. Maymon E, Romero R, Pacora P, Gomez R, Mazor M, Edwin S, et al. A role for the 72 kDa gelatinase (MMP-2) and its inhibitor (TIMP-2) in human parturition, premature rupture of membranes and intraamniotic infection. J Perinat Med. 2001;29:308-16.
267. Yoon BH, Oh SY, Romero R, Shim SS, Han SY, Park JS, et al. An elevated amniotic fluid matrix metalloproteinase-8 level at the time of mid-Trimester genetic amniocentesis is a risk factor for spontaneous preterm delivery. Am J Obstet Gynecol. 2001;185:1162-7.
268. Angus SR, Segel SY, Hsu CD, Locksmith GJ, Clark P, Sammel MD, et al. Amniotic fluid matrix metalloproteinase-8 indicates intra-Amniotic infection. Am J Obstet Gynecol. 2001;185:1232-8.
269. Romero R, Chaiworapongsa T, Espinoza J, Gomez R, Yoon BH, Edwin S, et al. Fetal plasma MMP-9 concentrations are elevated in preterm premature rupture of the membranes. Am J Obstet Gynecol. 2002;187:1125-30.
270. Moon JB, Kim JC, Yoon BH, Romero R, Kim G, Oh SY, et al. Amniotic fluid matrix metalloproteinase-8 and the development of cerebral palsy. J Perinat Med. 2002;30:301-6.
271. Helmig BR, Romero R, Espinoza J, Chaiworapongsa T, Bujold E, Gomez R, et al. Neutrophil elastase and secretory leukocyte protease inhibitor in prelabor rupture of membranes, parturition and intra-Amniotic infection. J Matern Fetal Neonatal Med. 2002;12:237-46.
272. Park KH, Chaiworapongsa T, Kim YM, Espinoza J, Yoshimatsu J, Edwin S, et al. Matrix metalloproteinase 3 in parturition, premature rupture of the membranes, and microbial invasion of the amniotic cavity. J Perinat Med. 2003;31:12-22.
273. Biggio JR Jr, Ramsey PS, Cliver SP, Lyon MD, Goldenberg RL, Wenstrom KD. Midtrimester amniotic fluid matrix metalloproteinase-8 (MMP-8) levels above the 90th percentile are a marker for subsequent preterm premature rupture of membranes. Am J Obstet Gynecol. 2005;192:109-13.
274. Nien JK, Yoon BH, Espinoza J, Kusanovic JP, Erez O, Soto E, et al. A rapid MMP-8 bedside test for the detection of intraamniotic inflammation identifies patients at risk for imminent preterm delivery. Am J Obstet Gynecol. 2006;195:1025-30.
275. Kim KW, Romero R, Park HS, Park CW, Shim SS, Jun JK, et al. A rapid matrix metalloproteinase-8 bedside test for the detection of intraamniotic inflammation in women with preterm premature rupture of membranes. Am J Obstet Gynecol. 2007;197:292.e1-5.
276. Kim SM, Lee J, Park C-W, Park JS, Jun JK, Yoon BH. One third of early spontaneous preterm delivery can be identified by a rapid matrix metalloproteinase-8 (MMP-8) bedside test at the time of mid-Trimester genetic amniocentesis (abstract 556). Am J Obstet Gynecol. 2015;212(Suppl):S277.
277. Park HS. The value of the genedia MMP-8 rapid test for diagnosing intraamniotic infection/inflammation and predicting adverse pregnancy outcomes in women with preterm premature rupture of membranes. Am J Obstet Gynecol. 2015;212(Suppl):S174.
278. Gomez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM. The fetal inflammatory response syndrome. Am J Obstet Gynecol. 1998;179:194-202.
279. Gotsch F, Romero R, Kusanovic JP, Mazaki-Tovi S, Pineles BL, Erez O, et al. The fetal inflammatory response syndrome. Clin Obstet Gynecol. 2007;50:652-83.
280. Yoon BH, Romero R, Kim KS, Park JS, Ki SH, Kim BI, et al. A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia. Am J Obstet Gynecol. 1999;181:773-9.
281. Dammann O, Leviton A. Role of the fetus in perinatal infection and neonatal brain damage. Curr Opin Pediatr. 2000;12:99-104.
282. Dammann O, Kuban KC, Leviton A. Perinatal infection, fetal inflammatory response, white matter damage, and cognitive limitations in children born preterm. Ment Retard Dev Disabil Res Rev. 2002;8:46-50.
283. Romero R, Espinoza J, Goncalves LF, Gomez R, Medina L, Silva M, et al. Fetal cardiac dysfunction in preterm premature rupture of membranes. J Matern Fetal Neonatal Med. 2004;16:146-57.
284. Kim YM, Romero R, Chaiworapongsa T, Espinoza J, Mor G, Kim CJ. Dermatitis as a component of the fetal inflammatory response syndrome is associated with activation of Tolllike receptors in epidermal keratinocytes. Histopathology. 2006;49:506-14.
285. Kim SK, Romero R, Chaiworapongsa T, Kusanovic JP, Mazaki-Tovi S, Mittal P, et al. Evidence of changes in the immunophenotype and metabolic characteristics (intracellular reactive oxygen radicals) of fetal, but not maternal, monocytes and granulocytes in the fetal inflammatory response syndrome. J Perinat Med. 2009;37:543-52.
286. Malaeb S, Dammann O. Fetal inflammatory response and brain injury in the preterm newborn. J Child Neurol. 2009;24:1119-26.
287. Romero R, Savasan ZA, Chaiworapongsa T, Berry SM, Kusanovic JP, Hassan SS, et al. Hematologic profile of the fetus with systemic inflammatory response syndrome. J Perinat Med. 2011;40:19-32.
288. Chaiworapongsa T, Romero R, Berry SM, Hassan SS, Yoon BH, Edwin S, et al. The role of granulocyte colony-stimulating factor in the neutrophilia observed in the fetal inflammatory response syndrome. J Perinat Med. 2011;39:653-66.
289. Romero R, Soto E, Berry SM, Hassan SS, Kusanovic JP, Yoon BH, et al. Blood pH and gases in fetuses in preterm labor with and without systemic inflammatory response syndrome. J Matern Fetal Neonatal Med. 2012;25:1160-70.
290. Romero R, Gomez R, Ghezzi F, Yoon BH, Mazor M, Edwin SS, et al. A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition. Am J Obstet Gynecol. 1998;179:186-93.
291. Malek TR, Bayer AL. Tolerance, not immunity, crucially depends on IL-2. Nat Rev Immunol. 2004;4:665-74.
292. Boyman O, Cho JH, Sprent J. The role of interleukin-2 in memory CD8 cell differentiation. Adv Exp Med Biol. 2010;684:28-41.
293. Kalia V, Sarkar S, Subramaniam S, Haining WN, Smith KA, Ahmed R. Prolonged interleukin-2Ralpha expression on virusspecific CD8+ T cells favors terminal-Effector differentiation in vivo. Immunity. 2010;32:91-103.
294. Pipkin ME, Sacks JA, Cruz-Guilloty F, Lichtenheld MG, Bevan MJ, Rao A. Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells. Immunity. 2010;32:79-90.
295. Pepper M, Pagan AJ, Igyarto BZ, Taylor JJ, Jenkins MK. Opposing signals from the Bcl6 transcription factor and the interleukin-2 receptor generate T helper 1 central and effector memory cells. Immunity. 2011;35:583-95.
296. Boyman O, Sprent J. The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol. 2012;12:180-90.
297. Gaynor ER, Vitek L, Sticklin L, Creekmore SP, Ferraro ME, Thomas JX Jr, et al. The hemodynamic effects of treatment with interleukin-2 and lymphokine-Activated killer cells. Ann Intern Med. 1988;109:953-8.
298. Ognibene FP, Rosenberg SA, Lotze M, Skibber J, Parker MM, Shelhamer JH, et al. Interleukin-2 administration causes reversible hemodynamic changes and left ventricular dysfunction similar to those seen in septic shock. Chest. 1988;94:750-4.
299. Hack CE, Wagstaff J, Strack van Schijndel RJ, Eerenberg AJ, Pinedo HM, Thijs LG, et al. Studies on the contact system of coagulation during therapy with high doses of recombinant IL-2: implications for septic shock. Thromb Haemost. 1991;65:497-503.
300. Hack CE, Ogilvie AC, Eisele B, Eerenberg AJ, Wagstaff J, Thijs LG. C1-inhibitor substitution therapy in septic shock and in the vascular leak syndrome induced by high doses of interleukin-2. Intensive Care Med. 1993;19(Suppl 1):S19-28.
301. Rosenstein M, Ettinghausen SE, Rosenberg SA. Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin 2. J Immunol. 1986;137:1735-42.
302. Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-Activated killer cells and interleukin-2 or high-Dose interleukin-2 alone. N Engl J Med. 1987;316:889-97.
303. Rosenberg SA, Lotze MT, Mule JJ. NIH conference. New approaches to the immunotherapy of cancer using interleukin-2. Ann Intern Med. 1988;108:853-64.
304. Kovacs EJ, Brock B, Varesio L, Young HA. IL-2 induction of IL-1 beta mRNA expression in monocytes. Regulation by agents that block second messenger pathways. J Immunol. 1989;143:3532-7.
305. Beutler B, Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med. 1987;316:379-85.
306. Dinarello CA. The proinflammatory cytokines interleukin-1 and tumor necrosis factor and treatment of the septic shock syndrome. J Infect Dis. 1991;163:1177-84.
307. Thijs LG, Hack CE, Strack van Schijndel RJ, Nuijens JH, Wolbink GJ, Eerenberg-Belmer AJ, et al. Complement activation and high-Dose of interleukin-2. Lancet. 1989;2:395.
308. Thijs LG, Hack CE, Strack van Schijndel RJ, Nuijens JH, Wolbink GJ, Eerenberg-Belmer AJ, et al. Activation of the complement system during immunotherapy with recombinant IL-2. Relation to the development of side effects. J Immunol. 1990;144:2419-24.
309. Vachino G, Gelfand JA, Atkins MB, Tamerius JD, Demchak P, Mier JW. Complement activation in cancer patients undergoing immunotherapy with interleukin-2 (IL-2): binding of complement and C-reactive protein by IL-2-Activated lymphocytes. Blood. 1991;78:2505-13.
310. Moore FD Jr, Schoof DD, Rodrick M, Eberlein TJ. The systemic complement activation caused by interleukin-2/lymphokineactivated killer-cell therapy of cancer causes minimal systemic neutrophil activation. Int J Cancer. 1991;49:504-8.
311. Baars JW, Hack CE, Wagstaff J, Eerenberg-Belmer AJ, Wolbink GJ, Thijs LG, et al. The activation of polymorphonuclear neutrophils and the complement system during immunotherapy with recombinant interleukin-2. Br J Cancer. 1992;65:96-101.
312. Sagone AL Jr, Husney RM, Triozzi PL, Rinehart J. Interleukin-2 therapy enhances salicylate oxidation by blood granulocytes. Blood. 1991;78:2931-6.
313. Baars JW, de Boer JP, Wagstaff J, Roem D, Eerenberg-Belmer AJ, Nauta J, et al. Interleukin-2 induces activation of coagulation and fibrinolysis: resemblance to the changes seen during experimental endotoxaemia. Br J Haematol. 1992;82:295-301.
314. Spear ML, Stefano JL, Fawcett P, Proujansky R. Soluble interleukin-2 receptor as a predictor of neonatal sepsis. J Pediatr. 1995;126:982-5.
315. Delogu G, Casula MA, Mancini P, Tellan G, Signore L. Serum neopterin and soluble interleukin-2 receptor for prediction of a shock state in gram-negative sepsis. J Crit Care. 1995;10:64-71.
316. Pierrakos C, Vincent JL. Sepsis biomarkers: a review. Crit Care. 2010;14:R15.
317. Fjell CD, Thair S, Hsu JL, Walley KR, Russell JA, Boyd J. Cytokines and signaling molecules predict clinical outcomes in sepsis. PLoS One. 2013;8:e79207.
318. Dalton DK, Pitts-Meek S, Keshav S, Figari IS, Bradley A, Stewart TA. Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science. 1993;259:1739-42.
319. Goodbourn S, Didcock L, Randall RE. Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. J Gen Virol. 2000;81:2341-64.
320. Lane HC, Fauci AS. Immunologic reconstitution in the acquired immunodeficiency syndrome. Ann Intern Med. 1985;103:714-8.
321. Kurzrock R, Quesada JR, Rosenblum MG, Sherwin SA, Gutterman JU. Phase I study of i.v. administered recombinant gamma interferon in cancer patients. Cancer Treat Rep. 1986;70:1357-64.
322. Horning SJ, Levine JF, Miller RA, Rosenberg SA, Merigan TC. Clinical and immunologic effects of recombinant leukocyte A interferon in eight patients with advanced cancer. J Am Med Assoc. 1982;247:1718-22.
323. Dinarello CA. Cytokines as endogenous pyrogens. J Infect Dis. 1999;179(Suppl 2):S294-304.
324. Helfgott DC, Tatter SB, Santhanam U, Clarick RH, Bhardwaj N, May LT, et al. Multiple forms of IFN-beta 2/IL-6 in serum and body fluids during acute bacterial infection. J Immunol. 1989;142:948-53.
325. Fong Y, Moldawer LL, Shires GT, Lowry SF. The biologic characteristics of cytokines and their implication in surgical injury. Surg Gynecol Obstet. 1990;170:363-78.
326. Schluter B, Konig B, Bergmann U, Muller FE, Konig W. Interleukin 6-A potential mediator of lethal sepsis after major thermal trauma: evidence for increased IL-6 production by peripheral blood mononuclear cells. J Trauma. 1991;31:1663-70.
327. Akira S, Kishimoto T. IL-6 and NF-IL6 in acute-phase response and viral infection. Immunol Rev. 1992;127:25-50.
328. Youn YK, LaLonde C, Demling R. The role of mediators in the response to thermal injury. World J Surg. 1992;16:30-6.
329. Pang G, Couch L, Batey R, Clancy R, Cripps A. GM-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, ICAM-1 and VCAM-1 gene expression and cytokine production in human duodenal fibroblasts stimulated with lipopolysaccharide, IL-1 alpha and TNF-Alpha. Clin Exp Immunol. 1994;96:437-43.
330. Jung HC, Eckmann L, Yang SK, Panja A, Fierer J, Morzycka-Wroblewska E, et al. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J Clin Invest. 1995;95:55-65.
331. Wei SQ, Fraser W, Luo ZC. Inflammatory cytokines and spontaneous preterm birth in asymptomatic women: a systematic review. Obstet Gynecol. 2010;116:393-401.
332. Evers AC, Nijhuis L, Koster MP, Bont LJ, Visser GH. Intrapartum fever at term: diagnostic markers to individualize the risk of fetal infection: a review. Obstet Gynecol Surv. 2012;67:187-200.
333. Goetzl L, Evans T, Rivers J, Suresh MS, Lieberman E. Elevated maternal and fetal serum interleukin-6 levels are associated with epidural fever. Am J Obstet Gynecol. 2002;187:834-8.
334. Wang LZ, Hu XX, Liu X, Qian P, Ge JM, Tang BL. Influence of epidural dexamethasone on maternal temperature and serum cytokine concentration after labor epidural analgesia. Int J Gynaecol Obstet. 2011;113:40-3.
335. Opsjln SL, Wathen NC, Tingulstad S, Wiedswang G, Sundan A, Waage A, et al. Tumor necrosis factor, interleukin-1, and interleukin-6 in normal human pregnancy. Am J Obstet Gynecol. 1993;169:397-404.
336. Austgulen R, Lien E, Liabakk NB, Jacobsen G, Arntzen KJ. Increased levels of cytokines and cytokine activity modifiers in normal pregnancy. Eur J Obstet Gynecol Reprod Biol. 1994;57:149-55.
337. Arntzen KJ, Lien E, Austgulen R. Maternal serum levels of interleukin-6 and clinical characteristics of normal delivery at term. Acta Obstet Gynecol Scand. 1997;76:55-60.
338. Greig PC, Murtha AP, Jimmerson CJ, Herbert WN, Roitman-Johnson B, Allen J. Maternal serum interleukin-6 during pregnancy and during term and preterm labor. Obstet Gynecol. 1997;90:465-9.
339. Hebisch G, Grauaug AA, Neumaier-Wagner PM, Stallmach T, Huch A, Huch R. The relationship between cervical dilatation, interleukin-6 and interleukin-8 during term labor. Acta Obstet Gynecol Scand. 2001;80:840-8.
340. Malamitsi-Puchner A, Protonotariou E, Boutsikou T, Makrakis E, Sarandakou A, Creatsas G. The influence of the mode of delivery on circulating cytokine concentrations in the perinatal period. Early Hum Dev. 2005;81:387-92.
341. Christiaens I, Zaragoza DB, Guilbert L, Robertson SA, Mitchell BF, Olson DM. Inflammatory processes in preterm and term parturition. J Reprod Immunol. 2008;79:50-7.
342. Unal ER, Cierny JT, Roedner C, Newman R, Goetzl L. Maternal inflammation in spontaneous term labor. Am J Obstet Gynecol. 2011;204:223.e1-5.
343. Cierny J, Unal E, Flood P, Rhee KY, Praktish A, Olson T, et al. Inflammatory cytokines, fever and term labor performance. Am J Obstet Gynecol. 2013;208:S144.
344. Cierny JT, Unal ER, Flood P, Rhee KY, Praktish A, Olson TH, et al. Maternal inflammatory markers and term labor performance. Am J Obstet Gynecol. 2014;210:447.e1-6.
345. Lee SE, Romero R, Jung H, Park CW, Park JS, Yoon BH. The intensity of the fetal inflammatory response in intraamniotic inflammation with and without microbial invasion of the amniotic cavity. Am J Obstet Gynecol. 2007;197:294.e1-6.
346. Armstrong-Wells J, Donnelly M, Post MD, Manco-Johnson MJ, Winn VD, Sebire G. Inflammatory predictors of neurologic disability after preterm premature rupture of membranes. Am J Obstet Gynecol. 2015;212:212.e1-9.
347. Romero R, Yoon BH, Mazor M, Gomez R, Gonzalez R, Diamond MP, et al. A comparative study of the diagnostic performance of amniotic fluid glucose, white blood cell count, interleukin-6, and gram stain in the detection of microbial invasion in patients with preterm premature rupture of membranes. Am J Obstet Gynecol. 1993;169:839-51.
348. Coultrip LL, Lien JM, Gomez R, Kapernick P, Khoury A, Grossman JH. The value of amniotic fluid interleukin-6 determination in patients with preterm labor and intact membranes in the detection of microbial invasion of the amniotic cavity. Am J Obstet Gynecol. 1994;171:901-11.
349. Greci LS, Gilson GJ, Nevils B, Izquierdo LA, Qualls CR, Curet LB. Is amniotic fluid analysis the key to preterm labor?. A model using interleukin-6 for predicting rapid delivery. Am J Obstet Gynecol. 1998;179:172-8.
350. El-Bastawissi AY, Williams MA, Riley DE, Hitti J, Krieger JN. Amniotic fluid interleukin-6 and preterm delivery: a review. Obstet Gynecol. 2000;95:1056-64.
351. Conde-Agudelo A, Papageorghiou AT, Kennedy SH, Villar J. Novel biomarkers for the prediction of the spontaneous preterm birth phenotype: a systematic review and meta-Analysis. BJOG. 2011;118:1042-54.
352. Cobo T, Kacerovsky M, Holst RM, Hougaard DM, Skogstrand K, Wennerholm UB, et al. Intra-Amniotic inflammation predicts microbial invasion of the amniotic cavity but not spontaneous preterm delivery in preterm prelabor membrane rupture. Acta Obstet Gynecol Scand. 2012;91:930-5.
353. Romero R, Kadar N, Miranda J, Korzeniewski SJ, Schwartz AG, Chaemsaithong P, et al. The diagnostic performance of the Mass Restricted (MR) score in the identification of microbial invasion of the amniotic cavity or intra-Amniotic inflammation is not superior to amniotic fluid interleukin-6. J Matern Fetal Neonatal Med. 2014;27:757-69.
354. Vousden N, Chandiramani M, Seed P, Shennan A. Interleukin-6 bedside testing in women at high risk of preterm birth. J Matern Fetal Neonatal Med. 2011;24:1301-4.
355. Kacerovsky M, Musilova I, Hornychova H, Kutova R, Pliskova L, Kostal M, et al. Bedside assessment of amniotic fluid interleukin-6 in preterm prelabor rupture of membranes. Am J Obstet Gynecol. 2014;211:385.e1-9.
356. Berthiaume M, Rousseau E, Rola-Pleszczynski M, Pasquier JC. Rapid evaluation of the absence of inflammation after rupture of membranes. J Matern Fetal Neonatal Med. 2014;27:865-9.
357. Lee SM, Romero R, Park JS, Chaemsaithong P, Jun JK, Yoon BH. A transcervical amniotic fluid collector: a new medical device for the assessment of amniotic fluid in patients with ruptured membranes. J Perinat Med. 2015;43:381-9.