Pathophysiology of endotoxin tolerance: Mechanisms and clinical consequences

Critical Care

Volumn 17, Issue 6, 2013, Pages 1-11

  López Collazo, Eduardo ^a   del Fresno, Carlos ^b  

^a HOSPITAL UNIVERSITARIO LA PAZ   (Spain)

^b CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CNIC   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ENDOTOXIN; INTERLEUKIN 1 RECEPTOR ASSOCIATED KINASE; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; INTERLEUKIN 10; INTERLEUKIN 6; LIPOPOLYSACCHARIDE; MICRORNA; MICRORNA 125B; MICRORNA 146A; MICRORNA 155; MICRORNA 221; MICRORNA 579; MICRORNA 98; MICRORNA LET 7E; MORPHINE; TOLL LIKE RECEPTOR 4; TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS 1; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ACUTE CORONARY SYNDROME; CYSTIC FIBROSIS; ENDOTOXIN TOLERANCE; EX VIVO STUDY; HUMAN; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; INNATE IMMUNITY; LETHAL DOSE; MACROPHAGE; MOLECULAR PATHOLOGY; MONOCYTE; NEOPLASM; NONHUMAN; PARATYPHOID FEVER; PATHOPHYSIOLOGY; PHAGOCYTOSIS; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SEPSIS; TUMOR ASSOCIATED LEUKOCYTE; TYPHOID FEVER; ANIMAL; CRITICAL ILLNESS; IMMUNOLOGY; PHYSIOLOGY;

ACUTE CORONARY SYNDROME; ANIMALS; CRITICAL ILLNESS; CYSTIC FIBROSIS; ENDOTOXINS; HUMANS; IMMUNE TOLERANCE; NEOPLASMS; SEPSIS;

EID: 84887530487     PISSN: 13648535     EISSN: 1466609X     Source Type: Journal    
DOI: 10.1186/cc13110     Document Type: Review

References (104)

1. Goldszmid RS, Trinchieri G. The price of immunity. Nat Immunol 2012, 13:932-938. 10.1038/ni.2422, 22990891.
2. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010, 11:373-384. 10.1038/ni.1863, 20404851.
3. Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol 2011, 30:16-34. 10.3109/08830185.2010.529976, 21235323.
4. Ramos HJ, Gale M. RIG-I like receptors and their signaling crosstalk in the regulation of antiviral immunity. Curr Opin Virol 2011, 1:167-176. 10.1016/j.coviro.2011.04.004, 3177754, 21949557.
5. Cavaillon JM, Adib-Conquy M. Bench-to-bedside review: Endotoxin tolerance as a model of leukocyte reprogramming in sepsis. Crit Care 2006, 10:233. 10.1186/cc5055, 1751079, 17044947.
6. Escoll P, del Fresno C, García L, Vallés G, Lendínez MJ, Arnalich F, López-Collazo E. Rapid up-regulation of IRAK-M expression following a second endotoxin challenge in human monocytes and in monocytes isolated from septic patients. Biochem Biophys Res Commun 2003, 311:465-472. 10.1016/j.bbrc.2003.10.019, 14592437.
7. del Fresno C, Gómez-Piña V, Lores V, Soares-Schanoski A, Fernández-Ruiz I, Rojo B, Alvarez-Sala R, Caballero-Garrido E, García F, Veliz T, Arnalich F, Fuentes-Prior P, García-Río F, López-Collazo E. Monocytes from cystic fibrosis patients are locked in an LPS tolerance state: down-regulation of TREM-1 as putative underlying mechanism. PLoS One 2008, 3:e2667. 10.1371/journal.pone.0002667, 2442190, 18628981.
8. del Fresno C, Soler-Rangel L, Soares-Schanoski A, Gómez-Piña V, González-León MC, Gómez-García L, Mendoza-Barberá E, Rodríguez-Rojas A, García F, Fuentes-Prior P, Arnalich F, López-Collazo E. Inflammatory responses associated with acute coronary syndrome up-regulate IRAK-M and induce endotoxin tolerance in circulating monocytes. J Endotoxin Res 2007, 13:39-52. 10.1177/0968051907078623, 17621545.
9. Lin CY, Tsai IF, Ho YP, Huang CT, Lin YC, Lin CJ, Tseng SC, Lin WP, Chen WT, Sheen IS. Endotoxemia contributes to the immune paralysis in patients with cirrhosis. J Hepatol 2007, 46:816-826. 10.1016/j.jhep.2006.12.018, 17328986.
10. Cavaillon JM, Adrie C, Fitting C, Adib-Conquy M. Reprogramming of circulatory cells in sepsis and SIRS. J Endotoxin Res 2005, 11:311-320.
11. Kox M, de Kleijn S, Pompe JC, Ramakers BP, Netea MG, van der Hoeven JG, Hoedemaekers CW, Pickkers P. Differential ex vivo and in vivo endotoxin tolerance kinetics following human endotoxemia. Crit Care Med 2011, 39:1866-1870. 10.1097/CCM.0b013e3182190d5d, 21494102.
12. Perry JA, Olver CS, Burnett RC, Avery AC. Cutting edge: the acquisition of TLR tolerance during malaria infection impacts T cell activation. J Immunol 2005, 174:5921-5925.
13. Greisman SE, Hornick RB, Wagner HN, Woodward WE, Woodward TE. The role of endotoxin during typhoid fever and tularemia in man. IV. The integrity of the endotoxin tolerance mechanisms during infection. J Clin Invest 1969, 48:613-629. 10.1172/JCI106020, 322267, 4886645.
14. Rubenstein M, Mulholland JH, Jeffery GM, Wolff SM. Malaria induced endotoxin tolerance. Proc Soc Exp Biol Med 1965, 118:283-287. 10.3181/00379727-118-29820, 14254570.
15. McCabe WR. Endotoxin tolerance. II. Its occurrence in patients with pyelonephritis. J Clin Invest 1963, 42:618-625. 10.1172/JCI104752, 289326, 16695902.
16. Neva FA, Morgan HR. Tolerance to the action of endotoxins of enteric bacilli in patients convalescent from typhoid and paratyphoid fevers. J Lab Clin Med 1950, 35:911-922.
17. Fuentes-Prior P, Biswas SK, López-Collazo E, Prados C, Arnalich F, Gutierrez Del Arroyo A, García-Rio F, Gómez-Piña V, Soares-Schanoski A, Fernández-Ruíz I, Jurado T, Kajiji T, Shu C, Marín E, del Fresno C. Potent phagocytic activity with impaired antigen presentation identifying lipopolysaccharide-tolerant human monocytes: demonstration in isolated monocytes from cystic fibrosis patients. J Immunol 2009, 182:6494-6507. 10.4049/jimmunol.0803350, 19414804.
18. Landoni VI, Chiarella P, Martire-Greco D, Schierloh P, Van-Rooijen N, Rearte B, Palermo MS, Isturiz MA, Fernandez GC. Tolerance to lipopolysaccharide promotes an enhanced neutrophil extracellular traps formation leading to a more efficient bacterial clearance in mice. Clin Exper Immunol 2012, 168:153-163.
19. Mendes ME, Baggio-Zappia GL, Brunialti MK, Fernandes Mda L, Rapozo MM, Salomao R. Differential expression of toll-like receptor signaling cascades in LPS-tolerant human peripheral blood mononuclear cells. Immunobiology 2011, 216:285-295. 10.1016/j.imbio.2010.07.008, 20828866.
20. Chen X, El Gazzar M, Yoza BK, McCall CE. The NF-kappaB factor RelB and histone H3 lysine methyltransferase G9a directly interact to generate epigenetic silencing in endotoxin tolerance. J Biol Chem 2009, 284:27857-27865. 10.1074/jbc.M109.000950, 2788836, 19690169.
21. Freudenberg MA, Galanos C. Induction of tolerance to lipopolysaccharide (LPS)-D-galactosamine lethality by pretreatment with LPS is mediated by macrophages. Infect Immun 1988, 56:1352-1357. 259829, 3356468.
22. Biswas SK, Lopez-Collazo E. Endotoxin tolerance: new mechanisms, molecules and clinical significance. Trends Immunol 2009, 30:475-487. 10.1016/j.it.2009.07.009, 19781994.
23. Karp CL, Wysocka M, Ma X, Marovich M, Factor RE, Nutman T, Armant M, Wahl L, Cuomo P, Trinchieri G. Potent suppression of IL-12 production from monocytes and dendritic cells during endotoxin tolerance. Eur J Immunol 1998, 28:3128-3136. 10.1002/(SICI)1521-4141(199810)28:10<3128::AID-IMMU3128>3.0.CO;2-T, 9808181.
24. Wolk K, Docke WD, von Baehr V, Volk HD, Sabat R. Impaired antigen presentation by human monocytes during endotoxin tolerance. Blood 2000, 96:218-223.
25. Lopez-Collazo E, Gomez-Pina V, Arnalich F. Understanding immune dysfunctions in sepsis patients. Crit Care 2010, 14:435. 10.1186/cc9202, 2945118, 20701813.
26. Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, Richards DR, McDonald-Smith GP, Gao H, Hennessy L, Finnerty CC, López CM, Honari S, Moore EE, Minei JP, Cuschieri J, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Jeschke MG, Klein MB, Gamelli RL, Gibran NS, Brownstein BH, Miller-Graziano C, Calvano SE, Mason PH, Cobb JP, Rahme LG, Lowry SF, Maier RV, Moldawer LL, Herndon DN, Davis RW, Xiao W, Tompkins RG. Inflammation and Host Response to Injury, Large Scale Collaborative Research Program: Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A 2013, 110:3507-3512. 10.1073/pnas.1222878110, 3587220, 23401516.
27. de Souza N. Model organisms: mouse models challenged. Nat Methods 2013, 10:288. 10.1038/nmeth.2429, 23653926.
28. Foster SL, Hargreaves DC, Medzhitov R. Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 2007, 447:972-978.
29. Pena OM, Pistolic J, Raj D, Fjell CD, Hancock RE. Endotoxin tolerance represents a distinctive state of alternative polarization (M2) in human mononuclear cells. J Immunol 2011, 186:7243-7254. 10.4049/jimmunol.1001952, 21576504.
30. Kobayashi K, Hernandez LD, Galan JE, Janeway CA, Medzhitov R, Flavell RA. IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 2002, 110:191-202. 10.1016/S0092-8674(02)00827-9, 12150927.
31. Peng Q, O'Loughlin JL, Humphrey MB. DOK3 negatively regulates LPS responses and endotoxin tolerance. PLoS One 2012, 7:e39967. 10.1371/journal.pone.0039967, 3384629, 22761938.
32. Calvano SE, Xiao W, Richards DR, Felciano RM, Baker HV, Cho RJ, Chen RO, Brownstein BH, Cobb JP, Tschoeke SK, Miller-Graziano C, Moldawer LL, Mindrinos MN, Davis RW, Tompkins RG, Lowry SF. Inflammation and Host Response to Injury, Large Scale Collaborative Research Program: A network-based analysis of systemic inflammation in humans. Nature 2005, 437:1032-1037. 10.1038/nature03985, 16136080.
33. Dominguez-Soto A, Sierra-Filardi E, Puig-Kroger A, Perez-Maceda B, Gomez-Aguado F, Corcuera MT, Sanchez-Mateos P, Corbi AL. Dendritic cell-specific ICAM-3-grabbing nonintegrin expression on M2-polarized and tumor-associated macrophages is macrophage-CSF dependent and enhanced by tumor-derived IL-6 and IL-10. J Immunol 2011, 186:2192-2200. 10.4049/jimmunol.1000475, 21239715.
34. del Fresno C, Otero K, Gómez-García L, González-León MC, Soler-Ranger L, Fuentes-Prior P, Escoll P, Baos R, Caveda L, García F, Arnalich F, López-Collazo E. Tumor cells deactivate human monocytes by up-regulating IL-1 receptor associated kinase-M expression via CD44 and TLR4. J Immunol 2005, 174:3032-3040.
35. Medvedev AE, Kopydlowski KM, Vogel SN. Inhibition of lipopolysaccharide-induced signal transduction in endotoxin-tolerized mouse macrophages: dysregulation of cytokine, chemokine, and toll-like receptor 2 and 4 gene expression. J Immunol 2000, 164:5564-5574.
36. Sato S, Takeuchi O, Fujita T, Tomizawa H, Takeda K, Akira S. A variety of microbial components induce tolerance to lipopolysaccharide by differentially affecting MyD88-dependent and -independent pathways. Int Immunol 2002, 14:783-791. 10.1093/intimm/dxf046, 12096038.
37. Dobrovolskaia MA, Medvedev AE, Thomas KE, Cuesta N, Toshchakov V, Ren T, Cody MJ, Michalek SM, Rice NR, Vogel SN. Induction of in vitro reprogramming by Toll-like receptor (TLR)2 and TLR4 agonists in murine macrophages: effects of TLR 'homotolerance' versus 'heterotolerance' on NF-kappa B signaling pathway components. J Immunol 2003, 170:508-519.
38. Biswas SK, Bist P, Dhillon MK, Kajiji T, Del Fresno C, Yamamoto M, Lopez-Collazo E, Akira S, Tergaonkar V. Role for MyD88-independent, TRIF pathway in lipid A/TLR4-induced endotoxin tolerance. J Immunol 2007, 179:4083-4092.
39. Frellstedt L, McKenzie HC, Barrett JG, Furr MO. Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro. Vet Immunol Immunopathol 2012, 149:97-102. 10.1016/j.vetimm.2012.05.012, 22658835.
40. Xiong Y, Medvedev AE. Induction of endotoxin tolerance in vivo inhibits activation of IRAK4 and increases negative regulators IRAK-M, SHIP-1, and A20. J Leukoc Biol 2011, 90:1141-1148. 10.1189/jlb.0611273, 3236548, 21934070.
41. Petzl W, Gunther J, Pfister T, Sauter-Louis C, Goetze L, von Aulock S, Hafner-Marx A, Schuberth HJ, Seyfert HM, Zerbe H. Lipopolysaccharide pretreatment of the udder protects against experimental Escherichia coli mastitis. Innate Immun 2012, 18:467-477. 10.1177/1753425911422407, 21990573.
42. Draisma A, Pickkers P, Bouw MP, van der Hoeven JG. Development of endotoxin tolerance in humans in vivo. Crit Care Med 2009, 37:1261-1267. 10.1097/CCM.0b013e31819c3c67, 19242351.
43. Grutz G. New insights into the molecular mechanism of interleukin-10-mediated immunosuppression. J Leukoc Biol 2005, 77:3-15.
44. Randow F, Syrbe U, Meisel C, Krausch D, Zuckermann H, Platzer C, Volk HD. Mechanism of endotoxin desensitization: involvement of interleukin 10 and transforming growth factor beta. J Exp Med 1995, 181:1887-1892. 10.1084/jem.181.5.1887, 2191997, 7722463.
45. Berg DJ, Kuhn R, Rajewsky K, Muller W, Menon S, Davidson N, Grunig G, Rennick D. Interleukin-10 is a central regulator of the response to LPS in murine models of endotoxic shock and the Shwartzman reaction but not endotoxin tolerance. J Clin Invest 1995, 96:2339-2347. 10.1172/JCI118290, 185885, 7593621.
46. Van der Poll T, de Vos AF, van den Pangaart PS, van Zoelen MA, de Kruif M, Birjmohun RS, Stroes ES, Van't Veer C. Induction of IRAK-M is associated with lipopolysaccharide tolerance in a human endotoxemia model. J Immunol 2007, 179:7110-7120.
47. Wiersinga WJ, van't Veer C, van den Pangaart PS, Dondorp AM, Day NP, Peacock SJ, van der Poll T. Immunosuppression associated with interleukin-1R-associated-kinase-M upregulation predicts mortality in Gram-negative sepsis (melioidosis). Crit Care Med 2009, 37:569-576. 10.1097/CCM.0b013e318194b1bf, 19114913.
48. Stiehm M, Peters K, Wiesmuller KH, Bufe A, Peters M. A novel synthetic lipopeptide is allergy-protective by the induction of LPS-tolerance. Clin Exp Allergy 2013, 43:785-797. 10.1111/cea.12116, 23786285.
49. Wesche H, Gao X, Li X, Kirschning CJ, Stark GR, Cao Z. IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family. J Biol Chem 1999, 274:19403-19410. 10.1074/jbc.274.27.19403, 10383454.
50. Janssens S, Beyaert R. Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members. Mol Cell 2003, 11:293-302. 10.1016/S1097-2765(03)00053-4, 12620219.
51. Mendoza-Barberá E, Corral-Rodríguez MA, Soares-Schanoski A, Velarde M, Macieira S, Messerschmidt A, López-Collazo E, Fuentes-Prior P. Contribution of globular death domains and unstructured linkers to MyD88.IRAK-4 heterodimer formation: an explanation for the antagonistic activity of MyD88s. Biochem Biophys Res Commun 2009, 380:183-187. 10.1016/j.bbrc.2009.01.069, 19167362.
52. López-Collazo E, Fuentes-Prior P, Arnalich F, del Fresno C. Pathophysiology of interleukin-1 receptor-associated kinase-M: implications in refractory state. Curr Opin Infect Dis 2006, 19:237-244. 10.1097/01.qco.0000224817.35105.7d, 16645484.
53. Domon H, Honda T, Oda T, Yoshie H, Yamazaki K. Early and preferential induction of IL-1 receptor-associated kinase-M in THP-1 cells by LPS derived from Porphyromonas gingivalis. J Leukoc Biol 2008, 83:672-679.
54. Liu ZJ, Yan LN, Li XH, Xu FL, Chen XF, You HB, Gong JP. Up-regulation of IRAK-M is essential for endotoxin tolerance induced by a low dose of lipopolysaccharide in Kupffer cells. J Surg Res 2008, 150:34-39. 10.1016/j.jss.2007.12.759, 18533191.
55. Gómez-Piña V, Martínez E, Fernández-Ruíz I, Del Fresno C, Soares-Schanoski A, Jurado T, Siliceo M, Toledano V, Fernández-Palomares R, García-Rio F, Arnalich F, Biswas SK, López-Collazo E. Role of MMPs in orchestrating inflammatory response in human monocytes via a TREM-1-PI3K-NF-kappaB pathway. J Leukoc Biol 2012, 91:933-945. 10.1189/jlb.0711340, 22459945.
56. Arts RJ, Joosten LA, van der Meer JW, Netea MG. TREM-1: intracellular signaling pathways and interaction with pattern recognition receptors. J Leukoc Biol 2013, 93:209-215. 10.1189/jlb.0312145, 23108097.
57. Quinn EM, Wang J, Redmond HP. The emerging role of microRNA in regulation of endotoxin tolerance. J Leukoc Biol 2012, 91:721-727. 10.1189/jlb.1111571, 22389313.
58. Broad A, Jones DE, Kirby JA. Toll-like receptor (TLR) response tolerance: a key physiological 'damage limitation' effect and an important potential opportunity for therapy. Curr Med Chem 2006, 13:2487-2502. 10.2174/092986706778201675, 17017906.
59. Moller K. Of cells and men: ex vivo and in vivo tolerance to lipopolysaccharide. Crit Care Med 2011, 39:1997-1998. 10.1097/CCM.0b013e3182249931, 21768803.
60. Buras JA, Holzmann B, Sitkovsky M. Animal models of sepsis: setting the stage. Nat Rev Drug Discov 2005, 4:854-865. 10.1038/nrd1854, 16224456.
61. van der Poll T, Opal SM. Host-pathogen interactions in sepsis. Lancet 2008, 8:32-43.
62. Monneret G, Venet F, Pachot A, Lepape A. Monitoring immune dysfunctions in the septic patient: a new skin for the old ceremony. Mol Med 2008, 14:64-78. 2078557, 18026569.
63. Munoz C, Carlet J, Fitting C, Misset B, Blériot JP, Cavaillon JM. Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest 1991, 88:1747-1754. 10.1172/JCI115493, 295719, 1939659.
64. Munoz C, Misset B, Fitting C, Bleriot JP, Carlet J, Cavaillon JM. Dissociation between plasma and monocyte-associated cytokines during sepsis. European J Immunol 1991, 21:2177-2184.
65. Pachot A, Lepape A, Vey S, Bienvenu J, Mougin B, Monneret G. Systemic transcriptional analysis in survivor and non-survivor septic shock patients: a preliminary study. Immunol Lett 2006, 106:63-71. 10.1016/j.imlet.2006.04.010, 16765452.
66. Manjuck J, Saha DC, Astiz M, Eales LJ, Rackow EC. Decreased response to recall antigens is associated with depressed costimulatory receptor expression in septic critically ill patients. J Lab Clin Med 2000, 135:153-160. 10.1067/mlc.2000.104306, 10695660.
67. Wysocka M, Robertson S, Riemann H, Caamano J, Hunter C, Mackiewicz A, Montaner LJ, Trinchieri G, Karp CL. IL-12 suppression during experimental endotoxin tolerance: dendritic cell loss and macrophage hyporesponsiveness. J Immunol 2001, 166:7504-7513.
68. Murphey ED, Sherwood ER. Bacterial clearance and mortality are not improved by a combination of IL-10 neutralization and IFN-gamma administration in a murine model of post-CLP immunosuppression. Shock 2006, 26:417-424. 10.1097/01.shk.0000226343.70904.4f, 16980891.
69. Abe R, Hirasawa H, Oda S, Sadahiro T, Nakamura M, Watanabe E, Nakada TA, Hatano M, Tokuhisa T. Up-regulation of interleukin-10 mRNA expression in peripheral leukocytes predicts poor outcome and diminished human leukocyte antigen-DR expression on monocytes in septic patients. J Surg Res 2008, 147:1-8. 10.1016/j.jss.2007.07.009, 17720196.
70. Rossato M, Curtale G, Tamassia N, Castellucci M, Mori L, Gasperini S, Mariotti B, De Luca M, Mirolo M, Cassatella MA, Locati M, Bazzoni F. IL-10-induced microRNA-187 negatively regulates TNF-alpha, IL-6, and IL-12p40 production in TLR4-stimulated monocytes. Proc Natl Acad Sci U S A 2012, 109:E3101-3110. 10.1073/pnas.1209100109, 3494907, 23071313.
71. Nathan C. Points of control in inflammation. Nature 2002, 420:846-852. 10.1038/nature01320, 12490957.
72. Ratjen F, Doring G. Cystic fibrosis. Lancet 2003, 361:681-689. 10.1016/S0140-6736(03)12567-6, 12606185.
73. Jain K, Smyth AR. Current dilemmas in antimicrobial therapy in cystic fibrosis. Expert Rev Respir Med 2012, 6:407-422. 10.1586/ers.12.39, 22971066.
74. Pier GB. The challenges and promises of new therapies for cystic fibrosis. J Exp Med 2012, 209:1235-1239. 10.1084/jem.20121248, 3444306, 22753926.
75. Hartl D, Gaggar A, Bruscia E, Hector A, Marcos V, Jung A, Greene C, McElvaney G, Mall M, Döring G. Innate immunity in cystic fibrosis lung disease. J Cyst Fibros 2012, 11:363-382. 10.1016/j.jcf.2012.07.003, 22917571.
76. del Campo R, Martínez E, del Fresno C, Alenda R, Gómez-Piña V, Fernández-Ruíz I, Siliceo M, Jurado T, Toledano V, Arnalich F, García-Río F, López-Collazo E. Translocated LPS might cause endotoxin tolerance in circulating monocytes of cystic fibrosis patients. PLoS One 2011, 6:e29577. 10.1371/journal.pone.0029577, 3247277, 22216320.
77. Ross R. Atherosclerosis - an inflammatory disease. N Engl J Med 1999, 340:115-126. 10.1056/NEJM199901143400207, 9887164.
78. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005, 352:1685-1695. 10.1056/NEJMra043430, 15843671.
79. Shishido T, Nozaki N, Yamaguchi S, Shibata Y, Nitobe J, Miyamoto T, Takahashi H, Arimoto T, Maeda K, Yamakawa M, Takeuchi O, Akira S, Takeishi Y, Kubota I. Toll-like receptor-2 modulates ventricular remodeling after myocardial infarction. Circulation 2003, 108:2905-2910. 10.1161/01.CIR.0000101921.93016.1C, 14656915.
80. Mach F, Schonbeck U, Bonnefoy JY, Pober JS, Libby P. Activation of monocyte/macrophage functions related to acute atheroma complication by ligation of CD40: induction of collagenase, stromelysin, and tissue factor. Circulation 1997, 96:396-399. 10.1161/01.CIR.96.2.396, 9244201.
81. Tang D, Kang R, Coyne CB, Zeh HJ, Lotze MT. PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunol Rev 2012, 249:158-175. 10.1111/j.1600-065X.2012.01146.x, 3662247, 22889221.
82. Arnalich F, Codoceo R, Lopez-Collazo E, Montiel C. Circulating cell-free mitochondrial DNA: a better early prognostic marker in patients with out-of-hospital cardiac arrest. Resuscitation 2012, 83:e162-e163. 10.1016/j.resuscitation.2012.03.032, 22490673.
83. Schon EA, DiMauro S, Hirano M. Human mitochondrial DNA: roles of inherited and somatic mutations. Nat Rev Genet 2012, 13:878-890.
84. Mantovani A, Sica A. Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol 2010, 22:231-237. 10.1016/j.coi.2010.01.009, 20144856.
85. Mantovani A, Sica A, Allavena P, Garlanda C, Locati M. Tumor-associated macrophages and the related myeloid-derived suppressor cells as a paradigm of the diversity of macrophage activation. Hum Immunol 2009, 70:325-330. 10.1016/j.humimm.2009.02.008, 19236898.
86. Soares-Schanoski A, Jurado T, Córdoba R, Siliceo M, Fresno CD, Gómez-Piña V, Toledano V, Vallejo-Cremades MT, Alfonso-Iñiguez S, Carballo-Palos A, Fernández-Ruiz I, Cubillas-Zapata C, Biswas SK, Arnalich F, García-Río F, López-Collazo E. Impaired antigen presentation and potent phagocytic activity identifying tumor-tolerant human monocytes. Biochem Biophys Res Commun 2012, 423:331-337. 10.1016/j.bbrc.2012.05.124, 22659741.
87. Nosari A. Infectious complications in chronic lymphocytic leukemia. Mediterr J Hematol Infect Dis 2012, 4:e2012070. 3507529, 23205258.
88. Mitsuhashi A, Goto H, Kuramoto T, Tabata S, Yukishige S, Abe S, Hanibuchi M, Kakiuchi S, Saijo A, Aono Y, Uehara H, Yano S, Ledford JG, Sone S, Nishioka Y. Surfactant protein A suppresses lung cancer progression by regulating the polarization of tumor-associated macrophages. Am J Pathol 2013, 182:1843-1853. 10.1016/j.ajpath.2013.01.030, 23499372.
89. Herrera M, Herrera A, Domínguez G, Silva J, García V, García JM, Gómez I, Soldevilla B, Muñoz C, Provencio M, Campos-Martin Y, García De Herreros A, Casal I, Bonilla F, Peña C. Cancer-associated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients. Cancer Sci 2013, 104:437-444. 10.1111/cas.12096, 23298232.
90. Lan C, Huang X, Lin S, Huang H, Cai Q, Wan T, Lu J, Liu J. Expression of M2-polarized macrophages is associated with poor prognosis for advanced epithelial ovarian cancer. Technol Cancer Res Treat 2013, 12:259-267.
91. Tang X, Mo C, Wang Y, Wei D, Xiao H. Anti-tumour strategies aiming to target tumour-associated macrophages. Immunology 2013, 138:93-104. 10.1111/imm.12023, 23113570.
92. Sica A, Rubino L, Mancino A, Larghi P, Porta C, Rimoldi M, Solinas G, Locati M, Allavena P, Mantovani A. Targeting tumour-associated macrophages. Expert Opin Ther Targets 2007, 11:1219-1229. 10.1517/14728222.11.9.1219, 17845147.
93. Miklossy J. Emerging roles of pathogens in Alzheimer disease. Expert Rev Mol Med 2011, 13:e30.
94. Grau AJ, Buggle F, Heindl S, Steichen-Wiehn C, Banerjee T, Maiwald M, Rohlfs M, Suhr H, Fiehn W, Becher H, Hacke W. Recent infection as a risk factor for cerebrovascular ischemia. Stroke 1995, 26:373-379. 10.1161/01.STR.26.3.373, 7886709.
95. Koennecke HC, Belz W, Berfelde D, Endres M, Fitzek S, Hamilton F, Kreitsch P, Mackert BM, Nabavi DG, Nolte CH, Pöhls W, Schmehl I, Schmitz B, von Brevern M, Walter G, Heuschmann PU, Berlin Stroke Register Investigators Factors influencing in-hospital mortality and morbidity in patients treated on a stroke unit. Neurology 2011, 77:965-972. 10.1212/WNL.0b013e31822dc795, 21865573, Berlin Stroke Register Investigators.
96. Meisel C, Meisel A. Suppressing immunosuppression after stroke. N Engl J Med 2011, 365:2134-2136. 10.1056/NEJMcibr1112454, 22129259.
97. Schulze J, Zierath D, Tanzi P, Cain K, Shibata D, Dressel A, Becker K. Severe stroke induces long-lasting alterations of high-mobility group box 1. Stroke 2013, 44:246-248. 10.1161/STROKEAHA.112.676072, 23204053.
98. Aneja RK, Tsung A, Sjodin H, Gefter JV, Delude RL, Billiar TR, Fink MP. Preconditioning with high mobility group box 1 (HMGB1) induces lipopolysaccharide (LPS) tolerance. J Leukoc Biol 2008, 84:1326-1334. 10.1189/jlb.0108030, 2567896, 18687905.
99. Zhang J, Takahashi HK, Liu K, Wake H, Liu R, Maruo T, Date I, Yoshino T, Ohtsuka A, Mori S, Nishibori M. Anti-high mobility group box-1 monoclonal antibody protects the blood-brain barrier from ischemia-induced disruption in rats. Stroke 2011, 42:1420-1428. 10.1161/STROKEAHA.110.598334, 21474801.
100. Tong H, Tang Y, Chen Y, Yuan F, Liu Z, Peng N, Tang L, Su L. HMGB1 activity inhibition alleviating liver injury in heatstroke. J Trauma Acute Care Surg 2013, 74:801-807. 10.1097/TA.0b013e31827e9a65, 23425738.
101. Bryant HU, Bernton EW, Holaday JW. Morphine pellet-induced immunomodulation in mice: temporal relationships. J Pharmacol Exp Ther 1988, 245:913-920.
102. Ocasio FM, Jiang Y, House SD, Chang SL. Chronic morphine accelerates the progression of lipopolysaccharide-induced sepsis to septic shock. J Neuroimmunol 2004, 149:90-100. 10.1016/j.jneuroim.2003.12.016, 15020069.
103. Breslow JM, Monroy MA, Daly JM, Meissler JJ, Gaughan J, Adler MW, Eisenstein TK. Morphine, but not trauma, sensitizes to systemic Acinetobacter baumannii infection. J Neuroimmune Pharmacol 2011, 6:551-565. 10.1007/s11481-011-9303-6, 21826405.
104. Banerjee S, Meng J, Das S, Krishnan A, Haworth J, Charboneau R, Zeng Y, Ramakrishnan S, Roy S. Morphine induced exacerbation of sepsis is mediated by tempering endotoxin tolerance through modulation of miR-146a. Sci Rep 1977, 2013:3.