Abstract
In severe sepsis, a network of proinflammatory cytokines (TNF, IL-lß, IL-6, IL-8) is activated and blood levels of these cytokines are elevated, albeit inconsistently and with large individual variations. In addition, elevated blood levels of anti-inflammatory cytokines (IL-10), as well as of soluble cytokine receptors (sTNF-RI and II, IL-lra), have been found. They seem to have a regulatory function in the host response. Levels of TNF and IL-6 are usually highest at the time of admission, whereas the time course of IL-lß levels (when detectable) can vary considerably. Limited data on IL-8 levels suggest that they may remain elevated for longer periods. Elevated levels of sTNFR and IL-lra may also persist for a prolonged period of time. The pathogenetic significance of these observations is still unclear, but persistingly high levels of proinflammatory cytokines may be associated with organ failure and mortality.
Similar content being viewed by others
References
Waage A, Halstensen A, Espevik T (1987) Association between tumour necrosis factor in serum and fatal out-come in patients with meningococcal disease. Lancet I:355–357
Girardin E, Grau GE, Dayer JM, Roux-Lombard P, the J 5 Study Group, Lambert PH (1988) Tumor necrosis factor and interleukin 1 in the serum of children with severe infectious purpura. N Engl J Med 319:397–400
de Groote MA, Martin MA, Densen P, Pfaller MA, Wenzel RP (1989) Plasma tumor necrosis factor levels in patients with presumed sepsis. JAMA 262: 249–251
Debets JMH, Kampmeijer R, van der Linden MPMH, Buurman WA, van der Linden CJ (1989) Plasma tumor necrosis factor and mortality in critically ill patients. Crit Care Med 17:489–494
Damas P, Reuter A, Gysen P, Demonty J, Lamy M, Franchimont P (1989) Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans. Crit Care Med 17:975–978
Calandra T, Baumgartner JD, Grau GE et al (1990) Prognostic values of tumor/cachectin, interleukin-1, interferon-α, and interferon-γ in the serum of patients with septic shock. J Infect Dis 161:982–987
Cannon JG, Tompkins RG, Gelfand JA et al (1990) Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J Infect Dis 161:79–84
Marks JD, Marks CB, Luce JM et al (1990) Plasma tumor necrosis factor in patients with septic shock. Am Rev Respir Dis 141:94–97
Munoz C, Misset B, Fitting C, Blériot JP, Carlet J, Cavaillon JM (1991) Dissociation between plasma and monocyte-associated cytokines during sepsis. Eur J Immunol 21:2177–2184
Philippé J, Dooijewaard G, Offner F, Turion P, Baele G, Leoux-Roels G (1992) Granulocyte elastase, tumor necrosis factor-α and urokinase levels as prognostic markers in severe infection. Thromb Haemostas 68:19–23
Wortel CH, von der Möhlen MAM, van Deventer SJH et al (1992) Effectiveness of a human monoclonal anti-endotoxin antibody (HA-1A) in gram-negative sepsis: relationship to endotoxin and cytokine levels. J Infect Dis 166: 1367–1374
Pinsky MR, Vincent J-L, Deviere J, Alegre M, Kahn RJ, Dupont E (1993) Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality. Chest 103: 565–575
Casey LC, Balk RA, Bone RC (1993) Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med 119:771–778
Van der Poll T, Jansen J, van Leenen D et al (1993) Release of soluble receptor for tumor necrosis factor in clinical sepsis and experimental endotoxemia. J Infect Dis 168:955–960
Martin C, Saux P, Mege J-L, Perrin G, Papazian L, Gouin F (1994) Prognostic values of serum cytokines in septic shock. Intensive Care Med 20:272–277
Girardin E, Roux-Lombard P, Grau GE et al (1992) Imbalance between tumor necrosis factor-alpha and soluble TNF receptor concentrations in severe meningococcaemia. Immunology 76:20–23
Rogy MA, Coyle SM, Oldenburg HSA et al (1994) Persistently elevated soluble tumor necrosis factor receptor and interleukin-1 receptor antagonist levels in critically ill patients. J Am Coll Surg 178:132–138
Damas P, Ledoux D, Nys M et al (1992) Cytokine serum level during severe sepsis in human IL-6 as a marker of severity. Ann Surg 215:356–362
Waage A, Brandtzaeg P, Halstensen A, Kierulf P, Espevik T (1989) The complex pattern of cytokines in serum from patients with meningococcal septic shock. Association between interleukin-6, interleukin-1, and fatal outcome. J Exp Med 169:333–338
Fischer E, Van Zee KJ, Marano MA et al (1992) Interleukin-1 receptor antagonist circulates in experimental inflammation and in human disease. Blood 79:2196–2200
Helfgott DC, Tatter SB, Santhanam U et al (1989) Multiple forms of β2/IL-6 in serum and body fluids during acute bacterial infection. J Immunol 142:948–953
Hack CE, De Groot ER, Felt-Bersma RJF et al (1989) Increased plasma levels of interleukin-6 in sepsis. Blood 74: 1704–1710
Calandra T, Gerain J, Heumann D, Baumgartner J-D, Glauser MP, the Swiss-Dutch J5 Immunoglobulin Study Group (1991) 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
Frieling JTM, van Deuren M, Wijdenes J, Van der Linden CJ, Sauerwein RW (1994) Soluble interleukin-6 (IL-6) receptor levels in septic patients and relation with circulating IL-6. Intensive Care Med 20 [Suppl 1]:S64
Friedland JS, Suputtamongkol Y, Remick DG et al (1992) Prolonged elevation of interleukin-8 and interleukin-6 concentrations in plasma and of leukocyte interleukin-8 mRNA levels during septicemic and localized Pseudomonas pseudomallei infection. Infect Immun 60:2402–2408
Hack CE, Hart M, Strack van Schijndel RJM et al (1992) Interleukin-8 in sepsis: relation to shock and inflammatory mediators. Infect Immun 60:2835–2842
Halstensen A, Ceska M, Brandtzaeg P, Redl H, Naess A, Waage A (1993) Interleukin-8 in serum and cerbrospinal fluid from patients with meningococcal disease. J Infect Dis 167:471–475
Chollet-Martin S, Montravers P, Gibert C (1993) High levels of interleukin-8 in the blood and alveolar spaces of patients with pneumonia and adult respiratory distress syndrome. Infect Immun 61:4553–4559
Marchant A, Devière J, Byl B, De Groote D, Vincent J-L, Goldman M (1994) Interleukin-10 production during septicaemia. Lancet 343:707–708
Bean AGD, Fierberg RA, Andrade S, Menon S, Zlotnik A (1993) Interleukin-10 protects mice against staphylococcal enterotoxin B-induced lethal shock. Infect Immun 61:4937–4939
Howard M, Muchamuel T, Andrade S, Menon S (1993) Interleukin-10 protects mice form lethal endotoxemia. J Exp Med 177:1205–1208