OYTOKINES IN THE PATHOGENESIS OF INFECTIOUS AND NONINFECTIOUS HUMAN DISEASES

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Abstract


Cytokines - family of polypeptide molecules, that are produced by tissue cells and regulate embryogenesis, some normal physiological functions, defense reactions to pathogens, and several pathological processes including immunopathology, carcinogenesis, heart and vascular pathology, etc. Different experiments led to conclusion that in case of hyperproduction cytokines instead of defense factors can become the mediators of pathology. During infections elevated cytokine synthesis followed with tissue inflammation depends on the pathogen associated molecular patterns binding to the pattern recognition innate immunity receptors. In non-infectious diseases like autoimmune, allergic, and other immunopathologic conditions cytokines also induce tissue inflammatory changes. In autoinflammatory diseases including metabolic syndrome elevated cytokine synthesis is due to endogenous danger molecules binding to pattern recognition receptors. In both cases cytokines can induce tissue and organ changes with the following development of the human disease clinical symptoms. Scientific studies in this field led to the so called cytokine theory of diseases, according to which cytokines are the main reason for pathology development. Due to this theory there are two principal variants of cytokine usage in clinical practice: cytokine therapy when recombinant cytokines are used to cure cytokine deficiency or their changed balance; and anticytokine therapy for inhibition of hyper produced endogenous cytokines.

A S Simbirtsev

State Research Institute of Highly Pure Biopreparations of the Federal Medico-Biological Agency

Email: simbirtsev@hpb-spb.com
St.-Petersburg

  1. Кетлинский С. А., Симбирцев А. С. Цитокины.- СПб.: Фолиант, 2008.- 552 с.
  2. Medzhitov R., Janeway C. Innate immunity: the virtues of a nonclonal system of recognition // Cell.- 1997.- Vol. 91.- P. 295-298.
  3. Matzinger P. The danger model: a renewed sense of self // Science.- 2002.- Vol. 296.- P.301-305
  4. Lemaitre B. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults // Cell.-1996.- Vol. 86.- P. 973-983.
  5. Poltorak A., He X., Smirnova I. et al. Defective LPS signaling in C3H/HeJ and C57Bl/10ScCr mice: mutations in Tlr4 gene // Science.-1998.- Vol. 282.- P. 2085-2088.
  6. Zarember K., Godowski P. Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines // J. Immunol.- 2002.- Vol. 168.- P. 554-561.
  7. Beutler B. Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases // Immunol. Rev.- 2009.- Vol. 227.-P. 248-263.
  8. Ting J., Lovering R., Alnemri E. et al. The NLR gene family: a standard nomenclature // Immunity.- 2008.- Vol. 28.- P. 285-287.
  9. Akira S., Takeda K. Toll-like receptor signaling // Nature Rev. Immunol.- 2004.- Vol. 4.- P. 499-511.
  10. Gay N., Keith F. Drosophila Toll and IL-1 receptor // Nature.- 1991.- Vol. 351.- P. 355-356.
  11. Caramalho I., Lopes-Carvalho T., Ostler D. et al. Regulatory T-cells selectively express Toll-like receptors and are activated by lipopolysaccharide // J. Exp. Med.- 2003.- Vol. 197.- P. 403-411.
  12. Kono H., Rock K. How dying cells alert the immune system to danger // Nat. Rev. Immunol.- 2008.- Vol. 8.- P.279-289
  13. Симбирцев А. С. Интерлейкин-1. Физиология, патология, клиника.- СПб.: Фолиант, 2011.- 480 с.
  14. Dinarello C. Immunological and Inflammatory Functions of the Interleukin-1 Family // Ann. Rev. Imm.- 2009.- Vol. 27.- P. 519-550.
  15. Wilson K. P., Black J. A., Thomson J. A. et al. Structure and mechanism of interleukin-1 beta converting enzyme // Nature.- 1994.-Vol. 370.- P. 270-273.
  16. Andrei C., Dazzi C., Lotti L. et al. The secretory route of the leaderless protein interleukin 1beta involves exocytosis of endolysosome-related vesicles // Mol. Biol. Cell.- 1999.- Vol. 10.- P. 1463-1475.
  17. Tschopp J., Martinon F., Burns K. NALPs: a novel protein family involved in inflammation // Nat. Rev. Mol. Cell Biol.- 2003.- Vol. 4.-P. 95-104.
  18. Martinon F., Tschopp J. Inflammatory caspases and inflammasomes: master switches of inflammation // Cell Death Differ.- 2007.- Vol. 14.-P. 10-22.
  19. Ye Z., Ting J. NLR, the nucleotide-binding domain leucine-rich repeat containing gene family // Curr. Opin. Immunol.- 2008.- Vol. 20.-P. 3-9.
  20. Pedra J., Cassel S., Sutterwala F. Sensing Pathogens and Danger Signals by the Inflammasome // Curr. Opin. Immunol.- 2009.- Vol. 21, № 1.- P. 10-16.
  21. Cassel S., Sutterwala F. Sterile inflammatory responses mediated by the NLRP3 inflammasome // Eur. J. Immunol.- 2010.- Vol. 40, № 3.- P. 607-611.
  22. Faustin B., Lartigue L., Bruey J. et al. Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation // Mol. Cell.-2007.- Vol. 25.- P. 713-724.
  23. Hsu L., Ali S., McGillivray S. et al. A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide // Proc. Natl. Acad. Sci. USA.- 2008.- Vol. 105.- P. 7803-7808.
  24. Miao E., Alpuche-Aranda C., Dors M. et al. Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf // Nat. Immunol.- 2006.- Vol. 7.- P. 569-575.
  25. Martinon F., Burns K., Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-1β // Mol. Cell.- 2002.- Vol. 10.- P. 417-426.
  26. Netea M. G., Nold-Petry C. A., Nold M. F. et al. Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages // Blood.- 2009.- Vol. 113.- P. 2324-2335.
  27. Соловьев М. М., Симбирцев А. С., Петропавловская О. Ю. и др. Препарат «Беталейкин» в лечении гнойно-воспалительных заболеваний челюстно-лицевой области // Terra Medica.- 2003.- № 2.- С.14-16
  28. Саламатов А. В., Баринов О. В., Синенченко А. Г. и др. Эффективность рекомбинантного ИЛ-1 бета в лечении гнойно-деструктивных заболеваний легких и плевры // Цитокины и воспаление.- 2006.- Т. 5, № 4.- С. 39-45.
  29. Азнабаева Л. Ф., Шарипова Э. Р., Арефьева Н. А., Зайнуллина А. Г. Иммуногенетические особенности продукции интерлейкина-1 бета при затяжной и хронической (рецидивирующей) форме бактериального воспаления верхних дыхательных путей (гнойного риносинусита) // Медицинская иммунология.- 2007.- Т. 9, № 4-5.- С. 535-540.
  30. Beck G., Habicht G. S., Benach J. L., Miller F. Interleukin-1: a common endogenous mediator of inflammation and the local Shwartzman reaction // J. Immunol.- 1986.- Vol. 136.- P. 3025-3031.
  31. Bone R, Sprung C., Sibbald W. Definitions for sepsis and organ failure // Crit. Care Med.- 1992.- Vol. 20.- P. 724-726.
  32. Levy M., Fink M., Marshall J. et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference // Crit. Care Med.- 2003.- Vol. 31.- P. 1250-1256.
  33. Cavaillon J.-M., Adib-Conquy M., Fitting C. Cytokine cascade in sepsis // Scand. J. Infect. Dis.- 2003.- Vol. 35.- P. 535-544.
  34. Van Dissel J., van Langevelde P., Westendorp R. et al. Anti-inflammatory cytokine profile and mortality in febrile patients // Lancet.- 1998.-Vol. 351.- P. 950-953.
  35. Monneret G. How to identify systemic sepsis-induced immunoparalysis // Adv. Sepsis.- 2005.- Vol. 4.- P. 42-49.
  36. McInnes I., Schett G. Cytokines in the pathogenesis of rheumatoid arthritis // Nat. Rev. Immunol.- 2007.- Vol. 7.- P. 429-442.
  37. Schulze-Koops H., Kalden J. The balance of Th1/Th2 cytokines in rheumatoid arthritis // Best Pract. Res. Clin. Rheumatol.- 2001.-Vol. 15.- P. 677-691.
  38. Lubberts E., Koenders M., van den Berg W. The role of T-cell interleukin-17 in conducting destructive arthritis: lessons from animal models // Arthritis Res. Ther.- 2005.- Vol. 7.- P. 29-37.
  39. Zhu S., Qian Y. IL-17/IL-17 receptor system in autoimmune disease // Clin.Science.- 2012.- Vol. 122.- P. 487-511.
  40. Ehrenstein M., Evans J., Singh A. et al. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNF alpha therapy // J. Exp. Med.- 2004.- Vol. 200.- P. 277-285.
  41. Nie H., Zheng Y., Li R. et al. Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-α in rheumatoid arthritis // Nature Med.- 2013.- Vol. 19.- P. 322-328.
  42. Horai R., Saijo S., Tanioka H. Development of chronic inflammatory artropathy resembling rheumatoid arthritis in interleukin-1 receptor antagonist deficient mice // J. Exp. Med.- 2000.- Vol. 191.- P. 313-320.
  43. Hoffman H., Rosengren S., Boyle D. et al. Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist // Lancet.- 2004.- Vol. 364.- P. 1779-1785.
  44. Ouchi N., Parker J., Lugus J., Walsh K. Adipokines in inflammation and metabolic disease // Nat.Rev.Immunol.- 2011.- Vol. 11.- P. 85-97.
  45. Lau D., Dhillon B., Yan H. et al. Adipokines: molecular links between obesity and atherosclerosis // Am. J. Physiol. Heart Circ. Physiol.- 2005.- Vol. 288.- P. 2031-2041.
  46. Bastard J., Jardel C., Bruckert E. et al. Elevated levels of interleukin-6 are reduced in serum and subcutaneous adipoise tissue of obese women after weight loss // J. Clin. Endocrinol. Metab.- 2000.- Vol. 85.- P. 3338-3342.
  47. Dandona P., Weinstock R., Thusu K. et al. Tumor necrosis factor-а in sera of obese patients: fall with weight loss // J.Clin.Endocrinol.Metab.- 1998.- Vol. 83.- P. 2907-2910.
  48. Vona-Davis L., Rose D. Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression // Endocrine-Related Cancer.- 2007.- Vol. 14.- P. 189-206.
  49. Vandanmagsar B., Youm Y.-H., Ravussin A. et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance // Nature Med.- 2011.- Vol. 17.- P. 179-188.
  50. McGonagle D., McDermott M. A proposed classification of the immunological diseases // PLoS Med.- 2006.- Vol. 3.- P. e297
  51. Mandrup-Poulsen T. Apoptotic signal transduction pathways in diabetes // Biochem. Pharmacol.- 2003.- Vol. 66.- P.1433-1440.
  52. Maedler K., Sergeev P., Ris F. et al. Glucose-induced beta-cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets // J. Clin. Invest.- 2002.- Vol. 110.- P. 851-860.
  53. Schroder K., Tschopp J. The inflammasomes // Cell.- 2010.- Vol. 140.- P. 821-832.
  54. De Nardo D., Latz E. NLRP3 inflammasomes link inflammation and metabolic disease // Trends Immunol.- 2011.- Vol. 32.-P. 373-379.
  55. Grant R., Dixit W. Mechanisms of disease: inflammasome activation and the development of type 2 diabetes // Front. Immunol.- 2013.-Vol. 4.- P. 50.
  56. Donath M., Shoelson S. Type 2 diabetes as an inflammatory disease // Nat. Rev. Immunol.- 2011.- Vol. 11.- P. 98-107.
  57. Larsen C., Faulenbach M., Vaag A. et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus // N. Engl. J. Med.- 2007.-Vol. 356.- P. 1517-1526.
  58. Monaco C., Paleolog E. Nuclear factor kappa B: a potential therapeutic target in atherosclerosis and thrombosis // Cardiovasc.Res.- 2004.-Vol. 61.- P. 671-682.
  59. Frostegard J., Ulfgren A., Nyberg P. et al. Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines // Atherosclerosis.- 1999.- Vol. 145.- P. 33-43.
  60. Lahoute C., Herbin O., Mallat Z., Tedgui A. Adaptive immunity in atherosclerosis: mechanisms and future therapeutic targets // Nat. Rev. Cardiology.- 2011.- Vol. 8.- P. 348-358.
  61. Frangogiannis N. The immune system and cardiac repair // Pharmacol.Res.- 2008.- Vol. 58.- P. 88-111.
  62. Arslan F., de Kleijn D., Pasterkamp G. Innate immune signaling in cardiac ischemia // Nature Reviews Cardiology.- 2011.- Vol. 8.-P. 292-300.
  63. Vinten-Johansen J. Involvement of neutrophils in the pathogenesis of lethal myocardial reperfusion injury // Cardiovasc. Res.- 2004.-Vol. 61.- P. 481-497.
  64. Ionita M., Arslan F., de Kleijn D., Pasterkamp G. Endogenous inflammatory molecules engage Toll-like receptors in cardiovascular disease // J. Innate. Immun.- 2010.- Vol. 2.- P. 307-315.
  65. Tsan M., Gao B. Endogenous ligands of Toll-like receptors // J. Leukoc. Biol.- 2004.- Vol. 76.- P. 514-519.
  66. Jordan J., Zhao Z., Vinten-Johansen J. The role of neutrophils in myocardial ischemia-reperfusion injury // Cardiovasc.Res.- 1999.-Vol. 43.- Р. 860-878.
  67. Sekido N., Mukaida N., Harada A. et al. Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against IL-8 // Nature.-1993.- Vol. 365.- P. 654-657.
  68. Lindahl B., Toss H., Siegbahn A. et al. Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease // New Engl. J. Med.- 2000.- Vol. 343.- Р. 1139-1147.
  69. Deten A., Volz H., Briest W. Zimmer H. Cardiac cytokine expression is up-regulated in the acute phase after myocardial infarction. Experimental studies in rats // Cardiovasc. Res.- 2002.- Vol. 55.- Р. 329-340.
  70. Takano H., Ohtsuka M., Akazawa H. et al. Pleiotropic effects of cytokines on acute myocardial infarction: G-CSF as a novel therapy for acute myocardial infarction // Curr. Pharmacol. Descriptions.- 2003.- Vol. 9.- Р. 1121-1127.
  71. Kovacic J., Muller D., Graham R. Actions and therapeutic potential of G-CSF and GM-CSF in cardiovascular disease // J. Mol. Cell. Cardiol.- 2007.- Vol. 42.- P. 19-33.
  72. Lipsic E., Schoemaker R., van der Meer P. et al. Protective effects of erythropoietin in cardiac ischemia: from bench to bedside // J. Am. Coll. Cardiol.- 2006.- Vol. 48.- P. 2161-2167.
  73. Tracey K. Physiology and immunology of the cholinergic antiinflammatory pathway // J. Clin. Invest.- 2007.- Vol. 117.- P. 289-296.
  74. Bennett I. et al. The effectiveness of hydrocortisone in the management of severe infection // JAMA.- 1963.- Vol. 183.- P. 462-465.
  75. Davis C., Brown K., Douglas H. et al. Prevention of death from endotoxin with antisera. I. The risk of fatal anaphylaxis to endotoxin // J. Immunol.- 1969.- Vol. 102.- P. 563-572.
  76. Tracey K., Fong Y., Hesse D. et al. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia // Nature.- 1987.- Vol. 330.- P. 662-664.
  77. Martinon F., Tschopp J. Inflammatory caspases and inflammasomes: master switches of inflammation // Cell Death Differ.- 2007.- Vol. 14.-P. 10-22.
  78. Симбирцев А. С. Достижения и перспективы использования рекомбинантных цитокинов в клинической практике // Медицинский академический журнал. - 2013. Т. 13, № 1. - С. 7-22.

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