Sepsis and apoptosis

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The article provides an overview of the current knowledge about the immune response in sepsis. Sepsis occurs on a background of development as a systemic inflammatory response, and immunosuppression phenomena. Dysfunction of the immune system is one of the most important parts of the pathophysiology and compulsory process. One of the immunosuppression mechanisms in sepsis is lymphocyte apoptosis. The article describes the main activation pathway of this process including those in neonatal sepsis.

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About the authors

Kh. S Khaertynov

Kazan State Medical University, Kazan, Russia

V. A Anokhin

Kazan State Medical University.

Kazan, Russia

S. V Boichuk

Kazan State Medical University.

Kazan, Russia

A. A Rizvanov

Kazan (Volga Region) Federal University

Kazan, Russia


  1. Stoll B.J., Hansen N.I., Sranchez P.J. et al. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics 2011; 127(5): 817-26.
  2. van den Berg J.P., Westerbeek E.A., van der Klis F.R. et al. Transplacental transport of IgG antibodies to preterm infants: a review of the literature. Early Hum.2011; 87: 67-72.
  3. Medzitov R. Toll-like receptors and innate immunity. NatureRev. Immunol. 2001; 1: 136-44.
  4. Симбирцев А.С., Громова А.Ю. Функциональный полиморфизм генов регуляторных механизмов воспаления. Цитокиныиво-спаление 2005; 1: 3-10.
  5. Chang Z.l. Important aspects of Toll-like receptors, ligands and their signaling pathways.Inflamm. Res. 2010; 59(10): 791-808.
  6. Tissieres P., Ochoda A., Dunn-Siegrist I. et al. Innate immune deficiency of extremely premature neonates can be reversed by interferon-y. PLOS ONE 2012; 7(3): e32863.
  7. Forster-Waldi E.K., Sadeghi D., Tamandl B. et al. Monocyte TLR4 expression and LPS-induced cytokine production increase during gestational aging. J. Pediatr. Res. 2005; 58: 121-4.
  8. Sadeghi K., Berger A., Langgartner M. et al. Immaturity of infection control in preterm and term newborns is associated with impaired toll-like receptor signaling. J. Infect. Dis. 2007; 195(2): 296-302.
  9. Melville J.M., Moss T.J. The immune consequences of preterm birth.Front. Neurosci.2013; 7: 79.
  10. Walker J.C., Smolders M.A., Gemen E.F. et al. Development of lympho- cyte subpopulations in preterm infants. Scand. J. Immunol. 2011; 73: 53-8.
  11. Hotchkiss R.S., Karl I.E. The pathophysiology and treatment of sepsis. NEJM 2003; 348(2):138-50.
  12. Савельев В.А., Гельфанд Б.Р., редакторы. Сепсис: классификация, клинико-диагностическая концепция и лечение. Москва: Медицинское информационное агентство; 2013.
  13. Bhandari V. Effective biomarkers for diagnosis of neonatal sepsis. J. Ped. Infect. Dis.Societ. 2014; 3(3): 234-45.
  14. PerezA., BellonJ.M., GurbindoM.D. etal. Impairment of stimulation ability of very-preterm neonatal monocytes in response to lipopolysaccharide. Hum. Immunol.2010; 71: 151-7.
  15. Самсыгина Г.А. О предрасполагающих факторах и факторах риска развития неонатального сепсиса и о современных подходах его лечения. Педиатрия 2012; 91(3): 32-7. 1 6. Белобородов В.Б. Иммунопатология тяжелого сепсиса и возможности ее коррекции. Вестник интенсивной терапии 2010; 4: 3-8.
  16. Белобородов В.Б. Иммунопатология тяжелого сепсиса и возможности ее коррекции. Вестник интенсивной терапии 2010; 4:
  17. DoughtyL., CarcilloJ.A., KaplanS. etal. The compensatory anti-inflammatory cytokine interleukin 10 response in pediatric sepsis-induced multiple organ failure.Chest.1998; 113: 1625-31.
  18. Romagnoli C., Frezza S., Cingolani A. et al. Plasma levels of interleukin-6 and interleukin-10 in preterm neonates evaluated for sepsis. Eur. J. Pediatr. 2001; 160: 345-50.
  19. Hotchkiss R.S., Monneret G., Payen D. Immunosuppression in sepsis: novel understanding of the disorder and a new therapeutic approach. Lancet Infect. Dis. 2013; 13: 260-8.
  20. Dellinger R.F., Levy M.M., Rhodes A. et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit. Care Med. 2013; 41(2): 580-637.
  21. Osuchowsky M.F., Welch K., Siddiqui J. et al. Circulating cytokine/inhibitor profiles reshape the understanding of the SIRS/ CARS continuum in sepsis and predict mortality. J. Immunol. 2006; 1: 1967-74.
  22. Delano M.J., Scumpia P.O., Weinstein J.S. et al. MyD88-dependent expansion of an immature GR-1(+) CD11b(+) population induces T cell suppression and Th2 polarization in sepsis. J. Exp. Med. 2007; 204: 1463-74.
  23. da Silva F.P., Nizet V. Cell death during sepsis: integration of disintegration in the inflammatory response to overwhelming infection. Apoptosis 2009; 14: 509-21.
  24. Elmore S. Apoptosis: a review of programmed cell death. Toxicol. Pathol. 2007; 35(4): 495-516.
  25. Hacker G. The morphology of apoptosis.Cell Tissue Res. 2000; 301: 5-17.
  26. Hotchkiss R.S., Coopersmith C.M., Karl I.E. Prevention of lymphosyt apoptosis - a potential treatment of sepsis? Clin. Inf. Diseases 2005; 41: 465-9.
  27. Boomer J.S., To K., Chang K.C. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA 2011; 306(23): 2594-605.
  28. Hotchkiss R.S., Tinsley K.W., Swanson P.E. et al. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J. Immunol. 2001; 166: 6952-63.
  29. Hotchkiss R.S., Tinsley K.W., Swanson P.E. et al. Depletion of dendritic cells, but not macrophages, in patients with sepsis. J. Immunol. 2002; 168: 2493-500.
  30. ХаертыновХ.С., БойчукС.В., АнохинВ.А. идр. Показатели активности апоптоза лимфоцитов крови у детей с неонатальным сепсисом. Гены и клетки 2014; 9(3): 267-71.
  31. Хаертынов Х.С., Бойчук С.В., Анохин В.А. и др. Апопотоз лимфоцитов крови у детей периода новорожденности с клебсиел-лезным сепсисом. Гены и клетки 2015; 10(4): 106-9.
  32. Pastille E., Didovic S., Brauckmann D. et al. Modulation of dendritic cell differentiation in the bone marrow mediates sustained immunosuppression after polymicrobial sepsis. J. Immunol. 2001; 186: 977-86.
  33. Biswas S.K., Lopez-Collazo E. Endotoxin tolerance: new mechanisms, molecules and clinical significance. Trends Immunol.2009; 30: 475-87.
  34. Monneret G., Venet F., Pachot A. et al. Monitoring immune dysfunctions in the septic patient: a new skin for the old ceremony. Mol. Med. 2008; 14: 64-78.
  35. Landelle C., Lepape A., Voirin N. et al.Low monocyte human leukocyte antigen-DR is independently associated with nosocomial infections after septic shock. Intensive Care Med. 2010; 36: 1859-66.
  36. Venet A., Lukaszewica A., Payen D. et al. Monitoring the immune response in sepsis: a rational approach to administration of immunoadjuvant therapies. Curr.Opin.Immunol.2013; 25: 477-83.
  37. Hotchkiss R.S., Swanson P.E.,Freeman B.D. et al. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit. Care Med. 1999; 27: 1230-51.
  38. Toti P., de Felice C.,Occhini R. et al. Spleen depletion in neonatal sepsis and chorioamnionitis. Am. J. Clin. Pathol.2004; 122: 765-71.
  39. Felmet K.A., Hall M.W., Clark R.S. et al. Prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia in children with nosocomial sepsis and multiple organ failure. J. Immunol. 2005; 174: 3765-72.
  40. Wesche D.E., Lomas-Neira J.L., Perl M. et al. Leukocyte apoptosis and its significance in sepsis and shock. J. Leuk.Biol. 2005; 78: 325-37.
  41. Drifte G., Dunn-Siegrist I., Tissieres P. et al. Innate immune functions of immature neutrophils in patients with sepsis and severe systemic inflammatory response syndrome. Crit. Care Med. 2013; 41, 820-32.
  42. Huang L.F., Yao Y.M.,Dong N. et al. Association between regulatory T cell activity and sepsis and outcome of severely burned patients: a prospective, observational study. Crit. Care 2010; 14: R3.
  43. Venet F., Pachot A.,Debard A.L. et al. Human CD4+CD25+ regulatory T lymphocytes inhibit lipopolysaccharide-induced monocyte survival through a Fas/Fas ligand-dependent mechanism. J. Immunol. 2006; 177: 6540-7.
  44. Hotchkiss R.S., Schmieg R.E., Swanson P.E. et al. Rapid onset of intestinal epithelial and lymphocyte apoptotic cell death in patients with trauma and shock. Crit. Care Med. 2000; 28: 3207-17.
  45. Hotchkiss R.S., Monneret G., Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Immunology 2013; 13: 862-74.
  46. Kasten K.R., Tschop J., Adediran S.G. et al. T cells are potent early mediators of the host response to sepsis. Shock 2010; 34(4): 327-36.
  47. Bochud P.Y., Calandra Th. Pathogenesis of sepsis: new concepts and implication for future treatment. BMJ 2003; 326(738): 262-5.
  48. Hargitai B., Szabo V., Hajdu J. et al. Apoptosis in various organs of preterm infants: histopathologic study of lung, kidney, liver, and brain of ventilated infants. Pediatr. Res. 2001; 50(1): 110-4.
  49. Coopersmith C.M., Stromberg P.E., Dunne W.M. et al. Inhibition of intestinal epithelial apoptosis and survival in a murine model of pneumonia-induced sepsis. JAMA 2002; 287: 1716-21.
  50. Unsinger J., Mc Glynn M., Kasten K.R. IL-7 Promotes T Cell viability, trafficking, and functionality and improves survival in sepsis. J. Immunol. 2010; 184(7): 3768-79.
  51. Inoue Sh., Unsinger J., Davis C.G. IL-15 Prevents Apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis. J. Immunol. 2010; 184(3): 1401-9.
  52. Chang K., Svabek C., Vazquez-Guillamet C. Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses T cell exhaustion in patients with sepsis. Critical Care 2014, 18(1): R3.
  53. Ward P. New approaches to the study of sepsis.EMBO Mol. Med. 2012; 4: 1234-43.
  54. Venet F., Foray A.P., Villars-MechinA. IL-7 Restores lymphocyte functions in septic patients. J. Immunol. 2012; 189: 5073-81

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