Skip to main content
SpringerLink
Log in

Clinical and biological significance of interleukin-10 plasma levels in patients with septic shock

  • Original Articles
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Interleukin-10 is a potent macrophage-deactivating cytokine that inhibits lipopolysaccharide-induced tumor necrosis factor production. We determined the plasma levels of immunoreactive interleukin-10 in 16 patients with septic shock and in 11 patients with circulatory shock of nonseptic origin. In septic shock, interleukin-10 levels peaked during the first 24 h (median: 48 pg/ml) and decreased progressively till Day 5. In nonseptic shock, interleukin-10 plasma levels also increased during the first 24 h but to a lesser extent (median: 17 pg/ml). In septic shock patients, interleukin-10 plasma levels were positively correlated with tumor necrosis factor (r=0.8,p=0.01) and with parameters of shock severity including lactate levels (r=0.56, p<0.05) and correlated negatively with blood platelet counts (r=−0.65,p<0.05). The decreased production of tumor necrosis factor-α and interleukin-6 afterin vitro incubation of whole blood from septic shock patients with lipopolysaccharide was not influenced byin vitro neutralization of interleukin-10. We conclude that interleukin-10 is produced in patients with circulatory shock of septic and nonseptic origin and that the production of this anti-inflammatory cytokine during septic shock correlates positively with the intensity of the inflammatory response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Glauser MP, Heumann D, Baumgartner JD, Cohen J: Pathogenesis and potential strategies for prevention and treatment of septic shock: an update. Clin Infect Dis 18 (suppl 2):S205–216, 1994

    PubMed  Google Scholar 

  2. Beutler B, Milsark IW, Cerami AC: Passive immunisation against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229:869–871, 1985

    PubMed  Google Scholar 

  3. Tracey KJ, Fong Y, Hesse DG, Manogue KR, Lee AT, Kuo GC, Lowry SF, Cerami A: Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteriaemia. Nature 330:662–664, 1987

    PubMed  Google Scholar 

  4. Mathison JC, Wolfson E, Ulevitch RJ: Participation of tumor necrosis factor in the mediation of gram-negative bacterial lipopolysaccharide-induced injury in rabbits. J Clin Invest 81:1925–1937, 1988

    PubMed  Google Scholar 

  5. Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O'Garra A: IL-10 inhibits cytokine production by activated macrophages. J Immunol 147:3815–3822, 1991

    PubMed  Google Scholar 

  6. Bogdan C, Vodovotz Y, Nathan C: Macrophage deactivation by interleukin 10: J Exp Med 174:1549–1555, 1991

    PubMed  Google Scholar 

  7. de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE: Interleukin-10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 174:1209–1220, 1991

    PubMed  Google Scholar 

  8. Gérard C, Bruyns C, Marchant A, Abramowicz D, Vandenabeele P, Delvaux A, Fiers W, Goldman M, Velu T: Interleukin-10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia. J Exp Med 177:547–550, 1993

    PubMed  Google Scholar 

  9. Howard M, Muchamuel T, Andrade S, Menon S: Interleukin 10 protects mice from lethal endotoxemia. J Exp Med 177:1205–1208, 1993

    PubMed  Google Scholar 

  10. Durez P, Abramowicz D, Gérard C, Van Mechelen M, Amraoui Z, Dubois C, Leo O, Velu T, Goldman M: In vivo induction of Interleukin-10 by anti-CD3 monoclonal antibody or bacterial lipopolysaccharide: differential modulation by cyclosporin A. J Exp Med 177:551–555, 1993

    PubMed  Google Scholar 

  11. Marchant A, Bruyns C, Vandenabeele P, Ducarme M, Gérard C, Delvaux A, De Groote D, Abramowicz D, Velu T, Goldman M: Interleukin-10 controls interferon-γ and tumor necrosis factor production during experimental endotoxemia. Eur J Immunol 24:1167–1171, 1994

    PubMed  Google Scholar 

  12. Marchant A, Devière J, Byl B, De Groote D, Vincent JL, Goldman M: Interleukin-10 production during septicaemia. Lancet 343:707–708, 1994

    PubMed  Google Scholar 

  13. De Groote D, Marchant A, Fauchet F, Jadoul M, Dehart I, Gérard C, Gevaert Y, Lopez M, Gathy R, Franssen JD, Radoux D, Franchimont P: Characterisation of monoclonal antibodies against human interleukin-10 and their use in an ELISA for the measurement of this cytokine. J Immunol Meth 177:225–234, 1994

    Google Scholar 

  14. Pradier O, Gérard C, Delvaux A, Lybin M, Abramowicz D, Capel P, Velu T, Goldman M: Interleukin-10 inhibits the induction of monocyte procoagulant activity by bacterial lipopolysaccharide. Eur J Immunol 23:2700–2703, 1993

    PubMed  Google Scholar 

  15. Pinsky MR, Vincent JL, Devière J, Alegre ML, Kahn RJ, Dupont E: Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality. Chest 103:565–575, 1993

    PubMed  Google Scholar 

  16. Damas P, Ledoux D, Nys M, Vrindts Y, De Groote D, Franchimont P, Lamy M: Cytokine serum level during severe sepsis in human: IL-6 as a marker of severity. Ann Surg 215:356–362, 1992

    PubMed  Google Scholar 

  17. Calandra T, Gerain J, Heumann D, Baumgartner JD, Glauser MP: High circulating levels of interleukin-6 in patients with septic shock: evolution during sepsis, prognostic value, and interplay with other cytokines. Am J Med 91:23–29, 1991

    PubMed  Google Scholar 

  18. van der Poll T, Marchant A, Berman L, Lazarus DD, Keogh CV, Nguyen L, Goldman M, Moldawer LL, Lowry SF: Endogenous interleukin-10 protects against death in septic peritonitis in mice. Surg Forum (in press)

  19. Wanidwonarum C, Strober W: Predominant role of tumor necrosis factor-alpha in human monocyte IL-10 synthesis: J Immunol 151:6853–6861, 1993

    PubMed  Google Scholar 

  20. van der Poll T, Jansen J, Levi M, ten Cate H, ten Cate JW, van Deventer SJH: Regulation of Interleukin 10 release by tumor necrosis factor in humans and chimpanzees. J Exp Med 180:1985–1988, 1994

    PubMed  Google Scholar 

  21. Munoz C, Carlet J, Fitting C, Misset B, Bleriot JP, Cavaillon JM: Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest 88:1747–1754, 1991

    PubMed  Google Scholar 

  22. Ertel W, Jarrar D, Jochum M, Thiele V, Kenney J, Faist E, Schildberg FW: Enhanced release of elastase is not concomitant with increased secretion of granulocyte-activating cytokines in whole blood from patients with sepsis. Arch Surg 129:90–98, 1994

    PubMed  Google Scholar 

  23. Setrakian JC, Yee J, Christou NV: Reduced tumor necrosis factor a production in lipopolysaccharide-treated whole blood from patients in the intensive care unit. Arch Surg 129:187–192, 1994

    PubMed  Google Scholar 

  24. Moore KW, O'Garra A, de Waal Malefyt R, Vieira P, Mosmann TR: Interleukin-10. Ann Rev Immunol 11:165–190, 1993

    Google Scholar 

  25. Ayala A, Deol ZK, Lehman DL, Herdon CD, Chaudry IH: Polymicrobial sepsis but not low-dose endotoxin infusion causes decreased splenocyte IL-2/IFN-g release while increasing IL-4/IL-10 production. J Surg Res 56:579–585, 1994

    PubMed  Google Scholar 

  26. Zuckerman SH, Evans GF, Snyder YM, Roeder WD: Endotoxinmacrophage interaction: post-translational regulation of tumor necrosis factor expression. J Immunol 143:1223–1227, 1989

    PubMed  Google Scholar 

  27. Mathison JC, Virca GD, Wolfson E, Tobias PS, Glaser K, Ulevitch RJ: Adaptation to bacterial lipopolysaccharide controls lipopolysaccharide-induced tumor necrosis factor production in rabbit macrophages. J Clin Invest 85:1108–1118, 1990

    PubMed  Google Scholar 

  28. Ziegler-Heitbrock HWL, Wedel A, Schraut W, Ströbel M, Wendelgass P, Sternsdorf T, Baüerle PA, Haas JG, Riethmüller G: Tolerance to lipopolysaccharide involves mobilization of nuclear factor kB with predominance of p50 homodimers. J Biol Chem 269:17001–17004, 1994

    PubMed  Google Scholar 

  29. Stefanova I, Corcoran ML, Horak EM, Wahl LM, Bolen JB, Horak ID: Lipopolysaccharide induces activation of CD14-associated protein tyrosine kinase p53/56lyn*. J Biol Chem 268:20725–20728, 1993

    PubMed  Google Scholar 

  30. Geng Y, Gulbins E, Altman A, Lotz M: Monocyte deactivation by interleukin 10 via inhibition of tyrosine kinase activity and the Ras signaling pathway. Proc Natl Acad Sci USA 91:8602–8606, 1994

    PubMed  Google Scholar 

  31. Beutler B, Grau GE: Tumor necrosis factor in the pathogenesis of infectious diseases. Crit Care Med 21:S423-S435, 1993

    PubMed  Google Scholar 

  32. Rabinovici R, John R, Esser KM, Vernick J, Feuerstein G: Serum tumor necrosis factor-alpha profile in trauma patients. J Trauma 35:698–702, 1993

    PubMed  Google Scholar 

  33. Roumen RMH, Hendriks T, van der Ven-Jongekrijg J, Nieuwenhuijzen GAP, Sauerwein RW, van der Meer JWM, Goris RJA: Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma. Ann Surg 218:769–776, 1993

    PubMed  Google Scholar 

  34. Basha MA, Meyer GS, Kunkel SL, Strieter RM, Rivers EP, J Popovich: Presence of tumor necrosis factor in humans undergoing cardiopulmonary resuscitation with return of spontaneous circulation. J Crit Care 6:185–189, 1991

    Google Scholar 

  35. Coletti LM, Remick DG, Burtch GD, Kunkel SL, Strieter RM, Campbell DA: Role of tumor necrosis factor-a in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat. J Clin Invest 85:1936–1943, 1990

    PubMed  Google Scholar 

  36. Baker JW, Deitch EA, Li M, Berg RD, Specian RD: Hemorrhagic shock induces bacterial translocation from the gut. J Trauma 28:896–906, 1988

    PubMed  Google Scholar 

  37. Rush BF, Sori AJ, Murphy TF, Smith S, Flanagan JJ, Machiedo GW: Endotoxemia and bacteremia during hemorrhagic shock: The link between trauma and sepsis. Ann Surg 207:549–554, 1988

    PubMed  Google Scholar 

  38. Abraham E, Chang YH: Haemorrhage-induced alterations in function and cytokine production of T cells and T cell subpopulations. Clin Exp Immunol 90:497–502, 1992

    PubMed  Google Scholar 

  39. Zingarelli B, Squadrito F, Altavilla D, Calapai G, Di Rosa M, Caputi AP: Role of tumor necrosis factor-α in acute hypovolemic hemorrhagic shock in rats. Am J Physiol 266:H1512-H1515, 1994

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Immunology, Hôpital Erasme, Université Libre de Bruxelles, 808 Route de Lennik, 1070, Brussels, Belgium

    A. Marchant, A. Hakim, G. Piérard & M. Goldman

  2. Department of Intensive Care, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium

    M. L. Alegre, G. Marécaux, G. Friedman, R. J. Kahn & J. L. Vincent

  3. Medgenix Research Group and Development, Fleurus, Belgium

    D. De Groote

Authors
  1. A. Marchant
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. L. Alegre
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Hakim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Piérard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Marécaux
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. Friedman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D. De Groote
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R. J. Kahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J. L. Vincent
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M. Goldman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marchant, A., Alegre, M.L., Hakim, A. et al. Clinical and biological significance of interleukin-10 plasma levels in patients with septic shock. J Clin Immunol 15, 266–273 (1995). https://doi.org/10.1007/BF01540884

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01540884

Key words

Search

Navigation