Clinical chorioamnionitis at term II: The intra-amniotic inflammatory response

Journal of Perinatal Medicine

Volumn 44, Issue 1, 2016, Pages 5-22

  Romero, Roberto ^a,b,c,d   Chaemsaithong, Piya ^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,e,f,g   Dong, Zhong ^a,e   Docheva, Nikolina ^a,e   Martinez Varea, Alicia ^a,e   Yoon, Bo Hyun ^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

Amniocentesis; chemokines; cytokines; funisitis; histologic chorioamnionitis; interleukin 6 (IL 6); intra amniotic infection inflammation; microbial invasion of the amniotic cavity (MIAC); polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR ESI MS); sterile inflammation

Indexed keywords

EOTAXIN 3; GAMMA INTERFERON; GAMMA INTERFERON INDUCIBLE PROTEIN 10; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 12P40; INTERLEUKIN 12P70; INTERLEUKIN 13; INTERLEUKIN 15; INTERLEUKIN 16; INTERLEUKIN 17; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 5; INTERLEUKIN 6; INTERLEUKIN 7; INTERLEUKIN 8; LYMPHOTOXIN; MACROPHAGE DERIVED CHEMOKINE; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MACROPHAGE INFLAMMATORY PROTEIN 1BETA; MONOCYTE CHEMOTACTIC PROTEIN 1; MONOCYTE CHEMOTACTIC PROTEIN 4; THYMUS AND ACTIVATION REGULATED CHEMOKINE; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN; AUTACOID; CHEMOKINE; CYTOKINE;

ADULT; AMNIOCENTESIS; AMNION FLUID ANALYSIS; AMNION FLUID LEVEL; ARTICLE; BACTERIUM DETECTION; CASE CONTROL STUDY; CHORIOAMNIONITIS; CLINICAL ARTICLE; CONTROLLED STUDY; CROSS-SECTIONAL STUDY; CYTOKINE RESPONSE; ELECTROSPRAY MASS SPECTROMETRY; FEMALE; GESTATIONAL AGE; HUMAN; IMMUNE RESPONSE; LABOR; MATERNAL AGE; POLYMERASE CHAIN REACTION; PRENATAL CARE; PRIORITY JOURNAL; RETROSPECTIVE STUDY; ADOLESCENT; AMNION FLUID; IMMUNOLOGY; METABOLISM; MICROBIOLOGY; NEWBORN; PREGNANCY; YOUNG ADULT;

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

EID: 84955317692     PISSN: 03005577     EISSN: 16193997     Source Type: Journal    
DOI: 10.1515/jpm-2015-0045     Document Type: Article

References (187)

1. Gibbs RS. Diagnosis of intra-Amniotic infection. Semin Perinatol. 1977;1:71-7.
2. MacVicar J. Chorioamnionitis. Clin Obstet Gynecol. 1970;13:272-90.
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. Hollander D. Diagnosis of chorioamnionitis. Clin Obstet Gynecol. 1986;29:816-25.
5. Gilstrap LC, 3rd, Cox SM. Acute chorioamnionitis. Obstet Gynecol Clin N Am. 1989;16:373-9.
6. Newton ER. Chorioamnionitis and intraamniotic infection. Clin Obstet Gynecol. 1993;36:795-808.
7. 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.
8. Tita AT, Andrews WW. Diagnosis and management of clinical chorioamnionitis. Clin Perinatol. 2010;37:339-54.
9. Fishman SG, Gelber SE. Evidence for the clinical management of chorioamnionitis. Semin Fetal Neonatal Med. 2012;17:46-50.
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. 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 Perinatal Med. 2015;43:19-36.
12. Romero R, Dey SK, Fisher SJ. Preterm labor: one syndrome, many causes. Science. 2014;345:760-5.
13. Sperling RS, Ramamurthy RS, Gibbs RS. A comparison of intrapartum versus immediate postpartum treatment of intraamniotic infection. Obstet Gynecol. 1987;70:861-5.
14. 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.
15. Gilstrap LC, 3rd, Leveno KJ, Cox SM, Burris JS, Mashburn M, Rosenfeld CR. Intrapartum treatment of acute chorioamnionitis: impact on neonatal sepsis. Am J Obstet Gynecol. 1988;159:579-83.
16. Maberry MC, Gilstrap LC, 3rd. Intrapartum antibiotic therapy for suspected intraamniotic infection: impact on the fetus and neonate. Clin Obstet Gynecol. 1991;34:345-51.
17. Westover T, Knuppel RA. Modern management of clinical chorioamnionitis. Infect Dis Obstet Gynecol. 1995;3:123-32.
18. Fahey JO. Clinical management of intra-Amniotic infection and chorioamnionitis: a review of the literature. J Midwifery Women s Health. 2008;53:227-35.
19. Chapman E, Reveiz L, Illanes E, Bonfill Cosp X. Antibiotic regimens for management of intra-Amniotic infection. Cochrane Database Syst Rev. 2014;12:CD010976.
20. Gordon H, Brosens I. Cytology of amniotic fluid: a new test for fetal maturity. Obstet Gynecol. 1967;30:652-6.
21. Morrison JC, Morrison DL, Lovett FA, Whybrew WD, Bucovaz ET, Wiser WL, et al. Nile blue staining of cells in amniotic fluid for fetal maturity. I. A reappraisal. Obstet Gynecol. 1974;44:355-61.
22. Morrison JC, Morrison DL, Lovett FA, Whybrew WD, Bucovaz ET, Wiser WL, et al. Nile blue staining of cells in amniotic fluid for fetal maturity. II. In complicated obstetric cases. Obstet Gynecol. 1974;44:362-7.
23. Woods JR, Jr., Maibach H. Cell surface lipid in the amniotic fluid. Obstet Gynecol. 1979;53:602-7.
24. 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.
25. 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.
26. DiGiulio DB, Gervasi M, Romero R, Mazaki-Tovi S, Vaisbuch E, Kusanovic JP, et al. Microbial invasion of the amniotic cavity in preeclampsia as assessed by cultivation and sequence-based methods. J Perinatal Med. 2010;38:503-13.
27. 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 Perinatal Med. 2010;38:495-502.
28. 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.
29. 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.
30. 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.
31. 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. 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.
33. 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-E15.
34. 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.
35. 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.
36. 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].
37. 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].
38. 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].
39. 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.
40. Yoon BH, Romero R, Park JS, Kim CJ, Kim SH, Choi JH, et al. Fetal exposure to an intra-Amniotic inflammation and the development of cerebral palsy at the age of three years. Am J Obstet Gynecol. 2000;182:675-81.
41. Redline RW, Heller D, Keating S, Kingdom J. Placental diagnostic criteria and clinical correlation-A workshop report. Placenta. 2005;26:S114-17.
42. Redline RW. Inflammatory responses in the placenta and umbilical cord. Semin Fetal Neonatal Med. 2006;11:296-301.
43. 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.
44. Lee Y, Kim HJ, Choi SJ, Oh SY, Kim JS, Roh CR, et al. Is there a stepwise increase in neonatal morbidities according to histological stage (or grade) of acute chorioamnionitis and funisitis?: effect of gestational age at delivery. J Perinatal Med. 2015;43:259-67.
45. 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.
46. 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 Perinatal Med. 2008;36:497-502.
47. Park HS, Romero R, Lee SM, Park CW, Jun JK, Yoon BH. Histologic chorioamnionitis is more common after spontaneous labor than after induced labor at term. Placenta. 2010;31:792-5.
48. 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 Perinatal Med. 2014;42:731-43.
49. 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. [Epub ahead of print].
50. 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.
51. 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.
52. Gotsch F, Romero R, Kusanovic JP, Mazaki-Tovi S, Pineles BL, Erez O, et al. The fetal inflammatory response syndrome. Clinical Obstet Gynecol. 2007;50:652-83.
53. 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 Perinatal Med. 2009;37:543-52.
54. Madsen-Bouterse SA, Romero R, Tarca AL, Kusanovic JP, Espinoza J, Kim CJ, et al. The transcriptome of the fetal inflammatory response syndrome. Am J Reprod Immunol. 2010;63:73-92.
55. 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 Perinatal Med. 2011;39:653-66.
56. Vaisbuch E, Romero R, Gomez R, Kusanovic JP, Mazaki-Tovi S, Chaiworapongsa T, et al. An elevated fetal interleukin-6 concentration can be observed in fetuses with anemia due to Rh alloimmunization: implications for the understanding of the fetal inflammatory response syndrome. J Matern Fetal Neonatal Med. 2011;24:391-6.
57. 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 Perinatal Med. 2011;40:19-32.
58. 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.
59. Stampalija T, Romero R, Korzeniewski SJ, Chaemsaithong P, Miranda J, Yeo L, et al. Soluble ST2 in the fetal inflammatory response syndrome: in vivo evidence of activation of the anti-inflammatory limb of the immune response. J Matern Fetal Neonatal Med. 2013;26:1384-93.
60. R Core Team. A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. Available at: http://www.R-project.org/. 2013 [cited 2014].
61. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B. 1995;57:289-300.
62. 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.
63. Casey ML, Cox SM, Word RA, MacDonald PC. Cytokines and infection-induced preterm labour. Reproduction, fertility, and development. Reprod Fertil Dev. 1990;2:499-509.
64. 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.
65. 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.
66. 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.
67. Gravett MG, Witkin SS, Haluska GJ, Edwards JL, Cook MJ, Novy MJ. An experimental model for intraamniotic infection and preterm labor in rhesus monkeys. Am J Obstet Gynecol. 1994;171:1660-7.
68. Gomez R, Ghezzi F, Romero R, Munoz H, Tolosa JE, Rojas I. Premature labor and intra-Amniotic infection. Clinical aspects and role of the cytokines in diagnosis and pathophysiology. Clin Perinatol. 1995;22:281-342.
69. Cox SM, Casey ML, MacDonald PC. Accumulation of interleukin-1beta and interleukin-6 in amniotic fluid: a sequela of labour at term and preterm. Hum Reprod Update. 1997;3:517-27.
70. Gonzalez-Bosquet E, Cerqueira MJ, Dominguez C, Gasser I, Bermejo B, Cabero L. Amniotic fluid glucose and cytokines values in the early diagnosis of amniotic infection in patients with preterm labor and intact membranes. J Matern Fetal Med. 1999;8:155-8.
71. Asrat T. Intra-Amniotic infection in patients with preterm prelabor rupture of membranes. Pathophysiology, detection, and management. Clin Perinatol. 2001;28:735-51.
72. Figueroa R, Garry D, Elimian A, Patel K, Sehgal PB, Tejani N. Evaluation of amniotic fluid cytokines in preterm labor and intact membranes. J Matern Fetal Neonatal Med. 2005;18: 241-7.
73. Sadowsky DW, Adams KM, Gravett MG, Witkin SS, Novy MJ. Preterm labor is induced by intraamniotic infusions of interleukin-1beta and tumor necrosis factor-Alpha but not by interleukin-6 or interleukin-8 in a nonhuman primate model. Am J Obstet Gynecol. 2006;195:1578-89.
74. Blank V, Hirsch E, Challis JR, Romero R, Lye SJ. Cytokine signaling, inflammation, innate immunity and preterm labour-A workshop report. Placenta. 2008;29:S102-4.
75. 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.
76. Puchner K, Iavazzo C, Gourgiotis D, Boutsikou M, Baka S, Hassiakos D, et al. Mid-Trimester amniotic fluid interleukins (IL-1beta, IL-10 and IL-18) as possible predictors of preterm delivery. In Vivo. 2011;25:141-8.
77. 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.
78. 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.
79. Leslie KK, Lee SL, Woodcock SM, Davies JK, McDuffie RS, Jr., Hirsch E, et al. Acute intrauterine infection results in an imbalance between pro-and anti-inflammatory cytokines in the pregnant rabbit. Am J Reprod Immunol. 2000;43:305-11.
80. Negishi H, Yamada H, Mikuni M, Kishida T, Okuyama K, Sagawa T, et al. Correlation between cytokine levels of amniotic fluid and histological chorioamnionitis in preterm delivery. J Perinatal Med. 1996;24:633-9.
81. Shobokshi A, Shaarawy M. Maternal serum and amniotic fluid cytokines in patients with preterm premature rupture of membranes with and without intrauterine infection. Int J Gynaecol Obstet. 2002;79:209-15.
82. 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.
83. 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.
84. Yoon BH, Romero R, Jun JK, Park KH, Park JD, Ghezzi F, et al. Amniotic fluid cytokines (interleukin-6, tumor necrosis factoralpha, interleukin-1 beta, and interleukin-8) and the risk for the development of bronchopulmonary dysplasia. Am J Obstet Gynecol. 1997;177:825-30.
85. 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.
86. 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.
87. 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.
88. Jacobsson B, Mattsby-Baltzer I, Andersch B, Bokstrom H, Holst RM, Wennerholm UB, et al. Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women in preterm labor. Acta Obstet Gynecol Scand. 2003;82:120-8.
89. Cobo T, Kacerovsky M, Palacio M, Hornychova H, Hougaard DM, Skogstrand K, et al. Intra-Amniotic inflammatory response in subgroups of women with preterm prelabor rupture of the membranes. PloS One. 2012;7:e43677.
90. 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.
91. 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.
92. 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.
93. 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 Foundation Symp. 1992;167:205-20; discussion 20-3.
94. 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.
95. Yoon BH, Romero R, Moon J, Chaiworapongsa T, Espinoza J, Kim YM, et al. Differences in the fetal interleukin-6 response to microbial invasion of the amniotic cavity between term and preterm gestation. J Matern Fetal Neonatal Med. 2003;13:32-8.
96. 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.
97. 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.
98. 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-E10.
99. Lencki SG, Maciulla MB, Eglinton GS. Maternal and umbilical cord serum interleukin levels in preterm labor with clinical chorioamnionitis. Am J Obstet Gynecol. 1994;170:1345-51.
100. Gargano JW, Holzman C, Senagore P, Thorsen P, Skogstrand K, Hougaard DM, et al. Mid-pregnancy circulating cytokine levels, histologic chorioamnionitis and spontaneous preterm birth. J Reprod Immunol. 2008;79:100-10.
101. 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 intraamniotic infection. Am J Obstet Gynecol 2015:[Epub ahead of print].
102. Romero R, Chaiworapongsa T, Kuivaniemi H, Tromp G. Bacterial vaginosis, the inflammatory response and the risk of preterm birth: a role for genetic epidemiology in the prevention of preterm birth. Am J Obstet Gynecol. 2004;190:1509-19.
103. Loppnow H, Werdan K, Reuter G, Flad HD. The interleukin-1 and interleukin-1 converting enzyme families in the cardiovascular system. Eur Cytokine Network. 1998;9:675-80.
104. Tato CM, Cua DJ. SnapShot: cytokines I. Cell. 2008;132:324, e1.
105. Turner MD, Nedjai B, Hurst T, Pennington DJ. Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta. 2014;1843:2563-82.
106. Tartaglia LA, Goeddel DV. Two TNF receptors. Immunol Today. 1992;13:151-3.
107. Rothe J, Gehr G, Loetscher H, Lesslauer W. Tumor necrosis factor receptors-structure and function. Immunol Res. 1992;11:81-90.
108. Smith CA, Farrah T, Goodwin RG. The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell. 1994;76:959-62.
109. Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell. 2001;104:487-501.
110. Arend WP, Palmer G, Gabay C. IL-1, IL-18, and IL-33 families of cytokines. Immunol Rev. 2008;223:20-38.
111. Tato CM, Cua DJ. SnapShot: cytokines III. Cell. 2008;132:900.
112. Topley N, Floege J, Wessel K, Hass R, Radeke HH, Kaever V, et al. Prostaglandin E2 production is synergistically increased in cultured human glomerular mesangial cells by combinations of IL-1 and tumor necrosis factor-Alpha 1. J Immunol. 1989;143:1989-95.
113. Romero R, Durum S, Dinarello CA, Oyarzun E, Hobbins JC, Mitchell MD. Interleukin-1 stimulates prostaglandin biosynthesis by human amnion. Prostaglandins. 1989;37:13-22.
114. 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, leukotrienes, and essential fatty acids. 1989;37:183-6.
115. Mitchell MD, Edwin S, Romero RJ. Prostaglandin biosynthesis by human decidual cells: effects of inflammatory mediators. Prostaglandins Leukot Essen Fatty Acids. 1990;41:35-8.
116. 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.
117. Romero R, Mazor M, Tartakovsky B. Systemic administration of interleukin-1 induces preterm parturition in mice. Am J Obstet Gynecol. 1991;165:969-71.
118. Mitchell MD, Romero RJ, Avila C, Foster JT, Edwin SS. Prostaglandin production by amnion and decidual cells in response to bacterial products. Prostaglandins Leukot Essen Fatty Acids. 1991;42:167-9.
119. Lundin-Schiller S, Mitchell MD. Prostaglandin production by human chorion laeve cells in response to inflammatory mediators. Placenta. 1991;12:353-63.
120. Ishihara O, Khan H, Sullivan MH, Elder MG. Interleukin-1 beta stimulates decidual stromal cell cyclo-oxygenase enzyme and prostaglandin production. Prostaglandins. 1992;44:43-52.
121. Romero R, Sepulveda W, Mazor M, Brandt F, Cotton DB, Dinarello CA, et al. The natural interleukin-1 receptor antagonist in term and preterm parturition. Am J Obstet Gynecol. 1992;167:863-72.
122. Mitchell MD, Edwin SS, Silver RM, Romero RJ. Potential agonist action of the interleukin-1 receptor antagonist protein: implications for treatment of women. J Clin Endocrinol Metab. 1993;76:1386-8.
123. Alleva DG, Burger CJ, Elgert KD. Tumor-induced regulation of suppressor macrophage nitric oxide and TNF-Alpha production. Role of tumor-Derived IL-10, TGF-beta, and prostaglandin E2. J Immunol. 1994;153:1674-86.
124. Mitchell MD, Romero RJ, Edwin SS, Trautman MS. Prostaglandins and parturition. Reprod Fertil Dev. 1995;7:623-32.
125. Brown NL, Alvi SA, Elder MG, Bennett PR, Sullivan MH. Regulation of prostaglandin production in intact fetal membranes by interleukin-1 and its receptor antagonist. J Endocrinol. 1998;159:519-26.
126. 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.
127. 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 Invest. 2002;9:215-19.
128. 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.
129. 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.
130. So T, Ito A, Sato T, Mori Y, Hirakawa S. Tumor necrosis factoralpha stimulates the biosynthesis of matrix metalloproteinases and plasminogen activator in cultured human chorionic cells. Biol Reprod. 1992;46:772-8.
131. Fortunato SJ, Menon R, Lombardi SJ. Collagenolytic enzymes (gelatinases) and their inhibitors in human amniochorionic membrane. Am J Obstet Gynecol. 1997;177:731-41.
132. Fortunato SJ, Menon R, Lombardi SJ. MMP/TIMP imbalance in amniotic fluid during PROM: an indirect support for endogenous pathway to membrane rupture. J Perinatal Med. 1999;27:362-8.
133. Arechavaleta-Velasco F, Ogando D, Parry S, Vadillo-Ortega F. Production of matrix metalloproteinase-9 in lipopolysaccharide-stimulated human amnion occurs through an autocrine and paracrine proinflammatory cytokine-Dependent system. Biol Reprod. 2002;67:1952-8.
134. 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 Perinatal Med. 2003;31:12-22.
135. Zaga V, Estrada-Gutierrez G, Beltran-Montoya J, Maida-Claros R, Lopez-Vancell R, Vadillo-Ortega F. Secretions of interleukin-1beta and tumor necrosis factor alpha by whole fetal membranes depend on initial interactions of amnion or choriodecidua with lipopolysaccharides or group B streptococci. Biol Reprod. 2004;71:1296-302.
136. Vadillo-Ortega F, Estrada-Gutierrez G. Role of matrix metalloproteinases in preterm labour. Br J Obstet Gynaecol. 2005;112:19-22.
137. Kumar D, Fung W, Moore RM, Pandey V, Fox J, Stetzer B, et al. Proinflammatory cytokines found in amniotic fluid induce collagen remodeling, apoptosis, and biophysical weakening of cultured human fetal membranes. Biol Reprod. 2006;74:29-34.
138. Oner C, Schatz F, Kizilay G, Murk W, Buchwalder LF, Kayisli UA, et al. Progestin-inflammatory cytokine interactions affect matrix metalloproteinase-1 and-3 expression in term decidual cells: implications for treatment of chorioamnionitis-induced preterm delivery. J Clin Endocrinol Metab. 2008;93:252-9.
139. Moore RM, Mansour JM, Redline RW, Mercer BM, Moore JJ. The physiology of fetal membrane rupture: insight gained from the determination of physical properties. Placenta. 2006;27:1037-51.
140. Chwalisz K, Benson M, Scholz P, Daum J, Beier HM, Hegele-Hartung C. Cervical ripening with the cytokines interleukin 8, interleukin 1 beta and tumour necrosis factor alpha in guineapigs. Hum Reprod. 1994;9:2173-81.
141. El Maradny E, Kanayama N, Kobayashi H, Hossain B, Khatun S, Liping S, et al. The role of hyaluronic acid as a mediator and regulator of cervical ripening. Hum Reprod. 1997;12:1080-8.
142. Watari M, Watari H, DiSanto ME, Chacko S, Shi GP, Strauss JF, 3rd. Pro-inflammatory cytokines induce expression of matrixmetabolizing enzymes in human cervical smooth muscle cells. Am J Pathol. 1999;154:1755-62.
143. Winkler M, Rath W. Changes in the cervical extracellular matrix during pregnancy and parturition. J Perinatal Med. 1999;27:45-60.
144. Watari M, Watari H, Nachamkin I, Strauss JF. Lipopolysaccharide induces expression of genes encoding pro-inflammatory cytokines and the elastin-Degrading enzyme, cathepsin S, in human cervical smooth-muscle cells. J Soc Gynecol Invest. 2000;7:190-8.
145. Fujimoto T, Savani RC, Watari M, Day AJ, Strauss JF, 3rd. Induction of the hyaluronic acid-binding protein, tumor necrosis factor-stimulated gene-6, in cervical smooth muscle cells by tumor necrosis factor-Alpha and prostaglandin E(2). Am J Pathol. 2002;160:1495-502.
146. Timmons B, Akins M, Mahendroo M. Cervical remodeling during pregnancy and parturition. Trends Endocrinol Metab. 2010;21:353-61.
147. Harder J, Bartels J, Christophers E, Schroder JM. A peptide antibiotic from human skin. Nature. 1997;387:861.
148. Singh PK, Jia HP, Wiles K, Hesselberth J, Liu L, Conway BA, et al. Production of beta-Defensins by human airway epithelia. Proc Natl Acad Sci USA. 1998;95:14961-6.
149. Weinberg A, Krisanaprakornkit S, Dale BA. Epithelial antimicrobial peptides: review and significance for oral applications. Crit Rev Oral Biol Med. 1998;9:399-414.
150. Schroder JM, Harder J. Human beta-Defensin-2. Int J Biochem Cell Biol. 1999;31:645-51.
151. Abiko Y, Mitamura J, Nishimura M, Muramatsu T, Inoue T, Shimono M, et al. Pattern of expression of beta-Defensins in oral squamous cell carcinoma. Cancer Lett. 1999;143:37-43.
152. Mathews M, Jia HP, Guthmiller JM, Losh G, Graham S, Johnson GK, et al. Production of beta-Defensin antimicrobial peptides by the oral mucosa and salivary glands. Infect Immunity. 1999;67:2740-5.
153. Harder J, Meyer-Hoffert U, Teran LM, Schwichtenberg L, Bartels J, Maune S, et al. Mucoid Pseudomonas aeruginosa, TNF-Alpha, and IL-1beta, but not IL-6, induce human beta-Defensin-2 in respiratory epithelia. Am J Resp Cell Mol Biol. 2000;22:714-21.
154. Dale BA, Krisanaprakornkit S. Defensin antimicrobial peptides in the oral cavity. J Oral Pathol Med. 2001;30:321-7.
155. Bajaj-Elliott M, Fedeli P, Smith GV, Domizio P, Maher L, Ali RS, et al. Modulation of host antimicrobial peptide (beta-Defensins 1 and 2) expression during gastritis. Gut. 2002;51:356-61.
156. Espinoza J, Chaiworapongsa T, Romero R, Edwin S, Rathnasabapathy C, Gomez R, et al. Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/ permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-Amniotic inflammation, preterm labor and premature rupture of membranes. J Matern Fetal Neonatal Med. 2003;13:2-21.
157. McDermott AM, Redfern RL, Zhang B, Pei Y, Huang L, Proske RJ. Defensin expression by the cornea: multiple signalling pathways mediate IL-1beta stimulation of hBD-2 expression by human corneal epithelial cells. Invest Ophthalmol Visual Sci. 2003;44:1859-65.
158. Liu L, Roberts AA, Ganz T. By IL-1 signaling, monocyte-Derived cells dramatically enhance the epidermal antimicrobial response to lipopolysaccharide. J Immunol. 2003;170:575-80.
159. Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF, et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol. 2003;171:3262-9.
160. Harder J, Meyer-Hoffert U, Wehkamp K, Schwichtenberg L, Schroder JM. Differential gene induction of human betadefensins (hBD-1,-2,-3, and-4) in keratinocytes is inhibited by retinoic acid. J Invest Dermatol. 2004;123:522-9.
161. Jang BC, Lim KJ, Paik JH, Kwon YK, Shin SW, Kim SC, et al. Upregulation of human beta-Defensin 2 by interleukin-1beta in A549 cells: involvement of PI3K, PKC, p38 MAPK, JNK, and NFkappaB. Biochem Biophys Res Commun. 2004;320:1026-33.
162. Jang BC, Lim KJ, Suh MH, Park JG, Suh SI. Dexamethasone suppresses interleukin-1beta-induced human beta-Defensin 2 mRNA expression: involvement of p38 MAPK, JNK, MKP-1, and NF-kappaB transcriptional factor in A549 cells. FEMS Immunol Med Microbiol. 2007;51:171-84.
163. Jang BC, Lim KJ, Choi IH, Suh MH, Park JG, Mun KC, et al. Triptolide suppresses interleukin-1beta-induced human betadefensin-2 mRNA expression through inhibition of transcriptional activation of NF-kappaB in A549 cells. Int J Mol Med. 2007;19:757-63.
164. Brandenburg LO, Varoga D, Nicolaeva N, Leib SL, Wilms H, Podschun R, et al. Role of glial cells in the functional expression of LL-37/rat cathelin-related antimicrobial peptide in meningitis. J Neuropathol Exp Neurol. 2008;67:1041-54.
165. Kim CJ, Romero R, Kusanovic JP, Yoo W, Dong Z, Topping V, et al. The frequency, clinical significance, and pathological features of chronic chorioamnionitis: a lesion associated with spontaneous preterm birth. Modern Pathol. 2010;23:1000-11.
166. Ogge G, Romero R, Lee DC, Gotsch F, Than NG, Lee J, et al. Chronic chorioamnionitis displays distinct alterations of the amniotic fluid proteome. J Pathol. 2011;223:553-65.
167. Romero R, Chaemsaithong P, Korzeniewski SJ, Kim CJ, Kim SJ, Gotsch F, et al. Elevated amniotic fluid concentrations of CXCL-10 without IL-6 is a biomarker for chronic placental inflammatory lesions and preterm delivery. Am J Obstet Gynecol (in preparation). 2015.
168. Chan SH, Perussia B, Gupta JW, Kobayashi M, Pospisil M, Young HA, et al. Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers. J Exp Med. 1991;173:869-79.
169. D Andrea A, Rengaraju M, Valiante NM, Chehimi J, Kubin M, Aste M, et al. Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells. J Exp Med. 1992;176:1387-98.
170. Morris SC, Madden KB, Adamovicz JJ, Gause WC, Hubbard BR, Gately MK, et al. Effects of IL-12 on in vivo cytokine gene expression and Ig isotype selection. J Immunol. 1994;152:1047-56.
171. Vinson DC, Thomas R, Kiser T. Association between epidural analgesia during labor and fever. J Fam Pract. 1993;36:617-22.
172. 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.
173. Herbst A, Wolner-Hanssen P, Ingemarsson I. Risk factors for fever in labor. Obstet Gynecol. 1995;86:790-4.
174. Ploeckinger B, Ulm MR, Chalubinski K, Gruber W. Epidural anaesthesia in labour: influence on surgical delivery rates, intrapartum fever and blood loss. Gynecol Obstet Invest. 1995;39:24-7.
175. Mayer DC, Chescheir NC, Spielman FJ. Increased intrapartum antibiotic administration associated with epidural analgesia in labor. Am J Perinatol. 1997;14:83-6.
176. 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.
177. Lieberman E, Lang JM, Frigoletto F, Jr., Richardson DK, Ringer SA, Cohen A. Epidural analgesia, intrapartum fever, and neonatal sepsis evaluation. Pediatrics. 1997;99:415-19.
178. Dashe JS, Rogers BB, McIntire DD, Leveno KJ. Epidural analgesia and intrapartum fever: placental findings. Obstet Gynecol. 1999;93:341-4.
179. Yancey MK, Zhang J, Schwarz J, Dietrich CS, 3rd, Klebanoff M. Labor epidural analgesia and intrapartum maternal hyperthermia. Obstet Gynecol. 2001;98:763-70.
180. Kaul B, Vallejo M, Ramanathan S, Mandell G. Epidural labor analgesia and neonatal sepsis evaluation rate: a quality improvement study. Anesth Analg. 2001;93:986-90.
181. 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.
182. 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.
183. Goetzl L, Zighelboim I, Badell M, Rivers J, Mastrangelo MA, Tweardy D, et al. Maternal corticosteroids to prevent intrauterine exposure to hyperthermia and inflammation: a randomized, double-blind, placebo-controlled trial. Am J Obstet Gynecol. 2006;195:1031-7.
184. Segal S. Labor epidural analgesia and maternal fever. Anesth Analg. 2010;111:1467-75.
185. Goetzl L, Manevich Y, Roedner C, Praktish A, Hebbar L, Townsend DM. Maternal and fetal oxidative stress and intrapartum term fever. Am J Obstet Gynecol. 2010;202:363.e1-5.
186. Goetzl L. Epidural analgesia and maternal fever: a clinical and research update. Curr Opin Anaesthesiol. 2012;25:292-9.
187. Goetzl L. Epidural fever in obstetric patients: it s a hot topic. Anesth Analg. 2014;118:494-5.