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Proinflammatory cytokine profile in children with neonatal sepsis

https://doi.org/10.21508/1027-4065-2017-62-5-93-100

Abstract

Research objective. Evaluation of inflammatory activity of the blood of newborns with various forms of bacterial infectious diseases with the determination of the diagnostic significance of various inflammatory markers.

Materials and methods. The study includes 50 newborns with various forms of infectious diseases: 31 newborns with neonatal sepsis (group 1) and 19 newborns with localized variants of bacterial infection. The severity of inflammatory activity was assessed by the level of C-reactive protein, the number of peripheral blood leukocytes, the level of cytokines-tumor necrosis factor-α (TNF-α), interleukins IL-2, IL-6, IL-8, IL-10, interferon-ɣ (IFN-ɣ), granulocyte-macrophage colony-stimulating factor (GM-CSF).

Results. In the group of children with neonatal sepsis, the first 2 days of the disease occur against the background of an increase in the concentration of TNF-α, IL-6, IL-8 and IFN-ɣ in the blood, the indices of which differed significantly (p <0.05) from the control group. Significant markers of inflammation were high concentrations in the blood of the C-reactive protein (RR-3.7, CI 1.7-8.1), IL-6 (RR-2.0, CI 1.4–3.0), and IL -8 (RR-1.5, CI 1.1–2.2). In the group of children with localized forms of bacterial infection, the first 2 days of the disease were accompanied by an increase in the concentration in the blood of TNF-α, IL-6 and IFN-ɣ (p <0.05). Moreover, the degree of increase of IL-6 was less pronounced than in the 1st group (p=0.007), and the median IL-8 did not differ from the control group (p=0,7).

Conclusion. The immune response for neonatal sepsis and localized forms of bacterial infection is characterized by an increase in the level of proinflammatory cytokines in the blood. Reliable markers of inflammation in sepsis are IL-6, IL-8 and C-reactive protein, the values of which were significantly high in the group of children with neonatal sepsis.

About the Authors

Kh. S. Khaertynov
Kazan State Medical University, Ministry of Health of the Russian Federation
Russian Federation


V. A. Anokhin
Kazan State Medical University, Ministry of Health of the Russian Federation
Russian Federation


A. A. Rizvanov
Kazan (Volga region) Federal University
Russian Federation


E. V. Martynova
Kazan (Volga region) Federal University
Russian Federation


S. A. Lubin
City Children’s Hospital No.1
Russian Federation


References

1. Verma P., Berwal P.K., Nagaraj N., Swami S., Jivaji P., Narayan S. Neonatal sepsis: epidemiology, clinical spectrum, recent antimicrobial agents and their antibiotic susceptibility pattern. Int J Contemp Pediatr 2015; 2: 176–180. DOI: 10.18203/2349-3291.ijcp20150523

2. Camacho-Gonzales A., Spearman P.W., Stoll B. J. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North A 2013; 60: 367–389. DOI: 10.1016/j.pcl.2012.12.003

3. Cortese F., Scicchitano P., Gesualdo M., Filaninno A., De Giorgi E. Early and Late Infections in Newborns: Where Do We Stand? A Review. Pediatr Neonatol 2016; 57: 265–273. DOI: 10.1016/j.pedneo.2015.09.007

4. Cuenca A.G., Wynn J.L., Moldawer L.L., Levy O. Role of Innate Immunity in Neonatal Infection. Am J Perinatol 2013; 30 (2): 105–112. DOI: 10.1055/s-0032-1333412

5. Самсыгина Г.А. Неонатальный сепсис. М: ПедиатрЪ 2014; 173 [Samsygina G.A. Neonatal sepsis. Moscow: PEDIATR 2014; 173. (in Russ)]

6. Rossi P., Botgros R., Shane T., Nadel S., Manzoni P., Arenas-Lopez S. Report on the Expert Meeting on Neonatal and Paediatric Sepsis. London: European Medicines Agency 2010. http://www.ema.europa.eu/docs/en GB/document library/Report/ 2010/12/WC500100199.pdf

7. Goldstein B., Giroir B., Randolph A. International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005; 6: 2–8. DOI: 10.1097/01.PCC.0000149131.72248.E6

8. Hornik C.P., Benjamin D.K., Becker K.C., Benjamin D.K.Jr., Li J., Clark R.H. et al. Use of the complete blood cell count in early-onset neonatal sepsis. Pediatr Infect Dis J 2012; 31: 799– 802. DOI: 10.1097/INF.0b013e318256905c.

9. Shah B.A., Padbury J.F. Neonatal sepsis: an old problem with new insights. Virulence 2014; 54: 449–457. DOI: 10.4161/viru.26906

10. Reinhart K., Bauer M., Riedemann N.C., Hartog C.S. New Approaches to Sepsis: Molecular Diagnostics and Biomarkers. Clin Microbiol Rev 2012; 25 (4): 609–634. DOI: 10.1128/CMR.00016-12

11. Hotchkiss R.S., Karl I.E. The pathophysiology and treatment of sepsis. New Engl J Med 2003; 348 (2): 138–150. DOI: 10.1056/NEJMra021333

12. Сепсис: классификация, клинико-диагностическая концепция и лечение. Под ред. В.А. Савельева, Б.Р. Гельфанда. М: Медицинское информационное агентство 2013; 353 [Sepsis: classification, clinical-diagnostic concept and treatment. V.A. Saveliev, B.R. Gelfand (eds). Moscow: Meditsinskoe informatsionnoe agentstvo 2013; 353. (in Russ)]

13. Torsvik M., Gustad L.T., Mehl A., Bangstad I.L., Vinje L.J., Damas J. K. et al. Early identification of sepsis in hospital inpatients by ward nurses increases 30-day survival. Critical Care 2016; 20: 244. DOI: 10.1186/s13054-016-1423-1.

14. Schulte W., Bernhagen J., Bucala R. Cytokines in Sepsis: Potent Immunoregulators and Potential Therapeutic Targets– An Updated View. Mediators Inflamm 2013; 2013: 165974. DOI: 10.1155/2013/165974

15. Медицинские лабораторные технологии. Руководство по клинической лабораторной диагностике. 3-е издание. Под ред. А.И. Карпищенко. М: ГЭОТАР-Медиа 2013; 353. [Medical laboratory technologies. A guide to clinical laboratory diagnostics. 3td ed. A.I. Karpishhenko (ed.). Moscow: GEOTAR-Media 2013; 353. (in Russ)]

16. Melville J.M., Moss T.J.M. The immune consequences of preterm birth. Front Neurosci 2013; 7: DOI: 10.3389/fnins.2013.00079

17. Chaudhry H., Zhou J., Zhong Y., Ali M.M., McGuire F., Nagarkatti P.S. et al. Role of Cytokines as a Double-edged Sword in Sepsis. In vivo 2013; 27: 669–684.

18. Lanziotti V.S., Povoa P., Soares M., Silva J.R.L., Barbosa A.P., Salluh J.I.F. Use of biomarkers in pediatric sepsis: literature review. Rev Bras Ter Intensiva 2016; 28 (4): 472– 482. DOI: 10.5935/0103-507X.20160080

19. Hou T., Huang D., Zeng R., Ye Z., Zhang Y. Accuracy of serum interleukin (IL)-6 in sepsis diagnosis: a systematic review and meta-analysis. Int J Clin Exp Med 2015; 8 (9): 15238– 15245.

20. Zhou M., Cheng S., Yu J., Lu Q. Interleukin-8 for Diagnosis of Neonatal Sepsis: A Meta- Analysis. PLoS ONE 2015; 10 (5): e0127170. DOI: 10.1371/journal.pone.0127170

21. Wong H.R., Cvijanovich N., Wheeler D.S., Bigham M.T., Monaco M., Odoms K. et al. Interleukin-8 as a stratification tool for interventional trials involving pediatric septic shock. Am J Respir Crit Care Med 2008; 178 (3): 276–282. DOI: 10.1164/rccm.200801-131OC.

22. Schoenborn J.R., Wilson C.B. Regulation of interferon gamma during innate and adaptive immune responses. Adv Immunol 2007; 96: 41–101. DOI: 10.1016/S0065- 2776(07)96002-2

23. Romero C.R., Herzig D.S., Etogo A., Nunez J., Mahmoudizad R., Fang G. et al. The role of interferon-gamma in the pathogenesis of acute intraabdominal sepsis. J Leuk Biol 2010; 88 (4): 725–735. DOI: 10.1189/jlb.0509307.

24. Leentjens J., Kox M., Koch R.M., Preijers F., Joosten L.A.B., van der Hoeven J.G. et al. Reversal of immunoparalysis in humans in vivo: a double-blind, placebo-controlled, randomized pilot study. Am J Respir Crit Med 2012; 186 (9): 838– 845. DOI: 10.1164/rccm.201204-0645OC.

25. Walker J.C., Smolders M.A., Gemen E.F., Antonius T.A., Leuvenink J., de Vries E. Development of lymphocyte subpopulations in preterm infants. Scand J Immunol 2011; 73: 53–58. DOI: 10.1111/j.1365-3083.2010.02473.x

26. Tatad A.M.F., Nesin M., Peaples J., Cheung S., Lin H., Sison C. et al. Cytokine expression in response to bacterial antigens in preterm and term infant cord blood monocytes. Neonatology 2008; 94: 8–15. DOI:10.1159/000112541

27. Lusyati S., Hulzebos C.V., Zandvoort J., Sauer P. Levels of 25 cytokines in the first seven days of life in newborn infants. BMC Research Notes 2013; 6: 547. DOI: 10.1186/1756-0500- 6-547

28. Bhandari V. Effective Biomarkers for Diagnosis of Neonatal Sepsis. J Pediatr Infect Dis Soc 2014; 3 (3): 234–245. DOI: 10.1093/jpids/piu063

29. Patil N.K., Bohannon J.K., Sterwood E.R. Immunotherapy: a promising approach to reverse sepsis-induced immunosuppression. Pharmacol Res 2016; 111: 688–702. DOI: 10.1016/j.phrs.2016.07.019.

30. Hotchkiss R.S., Osmon S.B., Chang K.C., Wagner T.H., Coopersmith C.M., Karl I.E. Accelerated lymphocyte death in sepsis occurs by both the death receptor and mitochondrial pathways. J Immunol 2005, 174: 5110–5118. DOI: 10.4049/jimmunol.174.8.5110

31. Хаертынов Х.С., Анохин В.А., Мустафин И.Г., Бойчук С.В., Сатрутдинов М.А., Андреева А.А. и др. Особенности иммунитета у новорожденных детей с локализованными и генерализованными формами бактериальных инфекций. Рос вестн перинатол и педиатр 2015; 60 (5): 168– 173. [Khaertynov H.S., Anohin V.A., Mustafin I.G., Bojchuk S.V., Satrutdinov M.A., Andreeva A.A. et al. Features of immunity in newborn children with localized and generalized forms of bacterial infections. Ros vestn perinatol i pediatr 2015; 60 (5): 168–173. (in Russ)]

32. Felmet K.A., Hall M. W., Clark R. S., Jaffe R., Carcillo J.A. Prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia in children with nosocomial sepsis and multiple organ failure. J Immunol 2005; 174: 3765–3772. DOI: 10.4049/jimmunol.174.6.3765

33. Hotchkiss R.S., Swanson P.E., Freeman B.D., Tinsley K.W., Cobb J.P., Matuschak G.M. et al. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med 1999; 27: 1230–1251. DOI: 10.1097/00003246-199907000-00002

34. Toti P., De Felice C., Occhini R., Schuerfeld K., Stumpo M., Epistolato M.C. et al. Spleen depletion in neonatal sepsis and chorioamnionitis. Am J Clin Pathol 2004; 122: 765–771. DOI: 10.1309/RV6E-9BMC-9954-A2WU

35. Otto G.P., Sossdorf M., Claus R.A., Rodel J., Menge K., Reinhart K. et al. The late phase of sepsis is characterized by an increased microbiological burden and death rate. Crit Care 2011; 15 (4): R183. DOI: 10.1186/cc10332.

36. Дегтярева М.В., Байбарина Е.Н., Солдатова И.Г., Ашиткова Н.В. Интерлейкин-2: опыт клинического применения в неонатологии. Санкт-Петербург: УльтраПринт 2016; 40. [Degtyareva M.V., Baibarina E.N., Soldatova I.G., Ashitkova N.V. Interleukin-2: clinical experience in neonatology. St. Petersburg: ULTRA PRINT 2016; 40. (in Russ)]

37. Venet F., Foray A.P., Villars-Méchin A., Malcus C., Poitevin-Later F., Lepape A. et al. IL-7 Restores Lymphocyte Functions in Septic Patients. J Immunol 2012; 189 (10): 5073– 5081. DOI: 10.4049/jimmunol.1202062

38. Unsinger J., Burnham C.A., McDonough J., Morre M., Prakash P.S., Caldwell C.C., Dunne W.M. Jr., Hotchkiss R.S. Interleukin- 7 Ameliorates Immune Dysfunction and Improves Survival in a 2-Hit Model of Fungal Sepsis. J Infect Dis 2012; 206: 606–616. DOI: 10.1093/infdis/jis383.

39. Shindo Y., Fuchs A.G., Davis C.G., Eitas T., Unsinger J., Burnham C.D. et al. Interleukin 7 immunotherapy improves host immunity and survival in a two-hit model of Pseudomonas aeruginosa pneumonia. J Leukoc Biol 2017 Feb; 101(2):543–554. DOI: 10.1189/jlb.4A1215-581R.

40. Innoue S., Unsinger J., Davis C.G., Muenzer J.T., Fergusson T.A., Chang K. et al. IL-15 prevent apoptosis, revers innate and adaptive immune dysfunction, and improves survival in sepsis. J Immunol 2010; 184 (3): 1401–1409. DOI: 10.4049/jimmunol.0902307.

41. Meisel C., Schefold J.C., Pschowski R., Baumann T., Hetzger K., Gregor J. et al. Granulocyte- macrophage colonystimulating factor to reverse sepsis-associated immunosuppression: a double- blind, randomized, placebo-controlled multicenter trial. Am J Respir Crit Care Med 2009; 180: 640– 648. DOI: 10.1164/rccm.200903-0363OC.

42. Nalos M., Santer-Nanan B., Parnell G., Tang B., McLean A.S., Nanan R. Immune effects of interferon gamma in persistent staphylococcal sepsis. Am J Respir Crit Care Med 2012; 185 (1): 110–112. DOI: 10.1164/ajrccm.185.1.110


Review

For citations:


Khaertynov Kh.S., Anokhin V.A., Rizvanov A.A., Martynova E.V., Lubin S.A. Proinflammatory cytokine profile in children with neonatal sepsis. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2017;62(5):93-100. (In Russ.) https://doi.org/10.21508/1027-4065-2017-62-5-93-100

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