NEW ASPECTS OF SEPSIS AND SEPTIC SHOCK PATHOGENESIS IN CHILDREN. THE COMPLEMENT SYSTEM AS TARGET FOR AN EFFECTIVE THERAPY

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Abstract

Nowadays sepsis is grave complication of infection end the cause of death reanimation. In this survey, we would like to emphasize the importance of the control over the activation over the compliment system. It has been proved of animal model a complement one of the key role in the development of hyperactive immunity response, later resulting in violation of immunity homeostasis. Mice which had C3–/–, C4–/– deficit, aft receiving a LPS dose intraperitoneallis showed a better survival to compare with the control group of animals. There exist clinical data which confirm active participation of the compliment in the chain of the septic process. The research showed the patient affected by sepsis, had protein C3 and C4 concentration correlating which mortality at the time of diagnosis. The is chemoattractants, protein C3a and C5a, turn tube the result of complements pathway activation. The chemoattractants, provoke the extraction a big number of cytokines. Vessels permeability increase and DIC-syndrome activation wis it, multiple organ dysfunction develops. Ishemiareperfusion launch triggers aseptic inflammation, which appears decentralization and DIC-syndrome. C1-INH controls the work of classical way complement and Hemostasis System. Researchers the deficit in C1-INH animals and patients affected bay sepsis, which is proved in laboratory and clinics. The remedy C1-INH (Berinert, CSL Behring) appeared over 25 years ago and was used and therapy hereditary angioedema. For the lasted years we accumulated a considerable quantity of fasts of C1-INH use which after pathologies: heart attack, Ischemia-reperfusion injury, trauma provoked by cardiopulmonary bypass. The use of C1-INH on animal models septic in clinical research their efficacy and safety.

About the authors

A. P. Prodeus

Speransky Children’s Hospital No. 9; Higher Medical School; I. Kant Baltic Federal University

Author for correspondence.
Email: prodeus@mail.ru

Andrei P. Prodeus - PhD, MD (Medicine), Professor, Head Pediatrician SChH No. 9; Head of the Department of Clinical Immunology and Allergology HMS; Visiting Professor I. Kant BFU.

123317, Moscow, Shmitovsky pr-d, 29, Speransky Children's  Hospital No. 9,  Phone/fax: +7 (499) 256-64-44 Russian Federation

M. V. Ustinova

Higher Medical School; I.M. Sechenov First Moscow State Medical University

Email: fake@neicon.ru

Undergraduate Student of Pediatric Faculty, I.M. Sechenov FMSMU; Laboratory Assistant, Department of Clinical Immunology and Allergology, HMS.

Moscow

Russian Federation

A. A. Korsunskiy

Speransky Children’s Hospital No. 9; I.M. Sechenov First Moscow State Medical University

Email: fake@neicon.ru

PhD, MD (Medicine), Professor, Chief Medical Officer SChHNo. 9; Head of Pediatrics and Children's Infectious Diseases Department, I.M. Sechenov FMSMU.

Moscow

Russian Federation

A. G. Goncharov

I. Kant Baltic Federal University

Email: fake@neicon.ru

PhD (Medicine), Immunologist, Director of the Living Systems Institute.

Kaliningrad

Russian Federation

References

  1. Черешнев В.А., Гусев Е.Ю. Иммунологические и патофизиологические механизмы системного воспаления // Медицинская иммунология. 2012. Т. 14, № 1–2. С. 9–20.
  2. Beltrame M.H., Boldt A.B., Catarino S.J., Mendes H.C., Boschmann S.E., Goeldner I., Messias-Reason I. MBL-associated serine proteases (MASPs) and infectious diseases. Mol. Immunol., 2015, vol. 67, iss. 1, pp. 85–100. doi: 10.1016/j.molimm.2015.03.245
  3. Caliezi C., Wuillenun W.A., Zeerleder S., Redondo M., Eisele B., Hack C.E. C1-Esterase inhibitor: an anti-inflammatory agent and its potential use in the treatment of diseases other than hereditary angioedema. Pharm. Rev., 2000, vol. 52, no. 1. pp. 92–112.
  4. Chan R.K., Ding G., Verna N., Ibrahim S., Oakes S., Austen Jr.W.G., Hechtman H.B., Moore Jr.F.D. IgM binding to injured tissue precedes complement activation during skeletal muscle ischemia-reperfusion. J. Surg. Res., 2004, vol. 122, no. 1, pp. 29–35. doi: 10.1016/j.jss.2004.07.005
  5. Charchaflieh J., Wei J., Labaze G., Hou Y.J., Babarsh B., Stutz H., Lee H., Worah S., Zhang M. The role of complement system in septic shock. Clin. Develop. Immunol., 2012, 8 p. doi: 10.1155/2012/407324
  6. Cinel I., Opal S.M. Molecular biology of inflammation and sepsis: a primer. Crit. Care Med., 2009, vol. 37, no. 1, pp. 291–304. doi: 10.1097/CCM.0b013e31819267fb
  7. Haeney M.R. The role of the complement cascade in sepsis. J. Antimicrob. Chemotherap., 1998, no. 41, iss. 1, pp. 41–46. doi: 10.1093/jac/41.suppl_1.41
  8. Hazelzet J.A., de Groot R., van Mierlo G., Joosten K.F., van der Voort E., Eerenberg A., Suur M.H., Hop W.C., Hack C.E. Complement activation in relation to capillary leakage in children with septic shock and purpura. Infect. Immun., 1998, vol. 66, no. 11, pp. 5350–5356.
  9. Hogasen A.K.M., Overlie I., Hansen T.W.R., Abrahamsen T.G., Finne P.H., Kolbjorn H. The analysis of the complement activation product is applicable in neonates in spite of their profound C9 deficiency. J. Perinat. Med., 2000, no. 28, pp. 39–48. doi: 10.1515/JPM.2000.006
  10. Karnaukhova E. C1-Esterase inhibitor: biological activities and therapeutic applications. J. Hematol. Thromb. Dis., 2013, vol. 1, iss. 3:113. doi: 10.4172/2329-8790.1000113
  11. Lupu F., Keshari R.S., Lambris J.D., Coggeshall K.M. Crosstalk between the coagulation and complement systems in sepsis. Thromb. Res., 2014, vol. 133, suppl. 1, pp. 28–31. doi: 10.1016/j.thromres.2014.03.014
  12. Markiewski M.M., Lambris J.D. The role of complement in inflammatory diseases from behind the scenes into the spotlight. Am. J. Pathol., 2007, vol. 171, iss. 3, pp. 715–727. doi: 10.2353/ajpath.2007.070166
  13. Pham H., Santucci S., William H.Y. Successful use of daily intravenous infusion of C1 esterase inhibitor concentrate in the treatment of a hereditary angioedema patient with ascites, hypovolemic shock, sepsis, renal and respiratory failure. Allergy Asthma Clin. Immunol., 2014, no. 10:62. doi: 10.1186/s13223-014-0062-9
  14. Prodeus A.P., Zhou X., Maurer M., Stephen J. G., Carroll C.C. Impaired mast cell-dependent natural immunity in complement C3-deficientmice. Nature, 1997, vol. 390, pp. 172–175. doi: 10.1038/36586
  15. Singer M., Deutschman C.S., Seymour C.W., Shankar-Hari M. The Third International Consensus definitions for sepsis and septic shock (Sepsis-3). JAMA, 2016, vol. 315, iss. 8, pp. 801–810. doi: 10.1001/jama.2016.0287
  16. Singer M., Jones A.M. Bench-to-bedside review: the role of C1-esterase inhibitor in sepsis and other critical illnesses. Crit. Care, 2011, no. 15:203. doi: 10.1186/cc9304
  17. Takahashi M., Iwaki D., Kanno K., Ishida Y., Xiong J., Matsushita M., Endo Y., Miura S., Ishii N., Sugamura K., Fujita T. Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 contributes to activation of the lectin complement pathway. J. Immunol., 2008, vol. 180, no. 9, pp. 6132–6138. doi: 10.4049/jimmunol.180.9.6132
  18. Tarnow-Mordi W., Isaacs D., Dutta S. Adjunctive immunologic interventions in neonatal sepsis. Clin. Perinat., 2010, vol. 37, iss. 2, pp. 481–499. doi: 10.1016/j.clp.2009.12.002
  19. Tassani P., Kunkel R., Richter J.A., Hannelore O., Hans P.L., Braun S.L., Eising G.P., Haas F., Paek S.U., Bauernschmitt R., Jochum M. Effect of C1-esterase-inhibitor on capillary leak and inflammatory response syndrome during arterial switch operations in neonates. J. Cardio. Vas. Anest., 2001, vol. 15, iss. 4, pp. 469–473. doi: 10.1053/jcan.2001.24989
  20. Walport M.J. Complement. N. Engl. J. Med., 2001, vol. 344, pp. 1058–1066. doi: 10.1056/NEJM200104053441406
  21. Zhang M., Takahashi K., Alicot E.M., Vorup-Jensen T., Kessler B., Thiel S., Jensenius J.C., Ezekowitz R.A.B., Moore F.D., Carroll M.C. Activation of the lectin pathway by natural IgM in a model of ischemia/reperfusion injury. J. Immunol., 2006, vol. 177, iss. 7, pp. 4727–4734. doi: 10.4049/jimmunol.177.7.4727

Copyright (c) 2018 Prodeus A.P., Ustinova M.V., Korsunskiy A.A., Goncharov A.G.

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