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Clin Diagn Lab Immunol. Mar 1996; 3(2): 175–183.
PMCID: PMC170271

Circulating complement proteins in patients with sepsis or systemic inflammatory response syndrome.

Abstract

The systemic inflammatory response of the body to invading microorganisms, termed sepsis, leads to profound activation of the complement system. Pathophysiological concepts suggest that complement activation occurs very early in this syndrome. Thus, we discuss whether the determination of concentrations of the complement components C3a, C5a, and C3 in plasma as well as of the C3a/C3 ratio might be helpful to diagnose sepsis early. For this purpose, 33 patients from an intensive care unit were monitored for 10 days. In comparison with healthy donors, C3a levels and the C3a/C3 ratio of intensive-care-unit patients were significantly elevated (P < 0.0001) on admission. In contrast, C3 levels were significantly reduced (P < 0.0001) but increased during the study. C5a levels in the plasma of healthy donors and patients were identical. Twenty-two of 33 patients fulfilled microbiological and clinical criteria of sepsis. Eleven patients had signs of systemic inflammatory response syndrome but no microbiological evidence of sepsis. The groups could be differentiated from each other by their C3a levels or their C3a/C3 ratios during the first 24 h after the clinical onset of sepsis (P < 0.05). Septic patients in shock had higher C3a levels than normotensive septic patients, although the differences were not significant. Nonsurvivors had significantly higher C3a levels on admission than survivors (P = 0.0185). No differences were found between septic patients who developed adult respiratory distress syndrome and those who did not. Thus, determination of C3a concentrations in plasma may prove useful (i) to diagnose sepsis early, (ii) to differentiate between patients with sepsis and those with systemic inflammatory response syndrome, and (iii) to assess prognosis.

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Selected References

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  • Barton PA, Warren JS. Complement component C5 modulates the systemic tumor necrosis factor response in murine endotoxic shock. Infect Immun. 1993 Apr;61(4):1474–1481. [PMC free article] [PubMed]
  • Bengtson A, Heideman M. Anaphylatoxin formation in sepsis. Arch Surg. 1988 May;123(5):645–649. [PubMed]
  • Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. [PubMed]
  • Bhakdi S, Fassbender W, Hugo F, Carreno MP, Berstecher C, Malasit P, Kazatchkine MD. Relative inefficiency of terminal complement activation. J Immunol. 1988 Nov 1;141(9):3117–3122. [PubMed]
  • Björk J, Hugli TE, Smedegård G. Microvascular effects of anaphylatoxins C3a and C5a. J Immunol. 1985 Feb;134(2):1115–1119. [PubMed]
  • Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992 Jun;101(6):1644–1655. [PubMed]
  • Cochrane CG, Müller-Eberhard HJ. The derivation of two distinct anaphylatoxin activities from the third and fifth components of human complement. J Exp Med. 1968 Feb 1;127(2):371–386. [PMC free article] [PubMed]
  • Duchateau J, Haas M, Schreyen H, Radoux L, Sprangers I, Noel FX, Braun M, Lamy M. Complement activation in patients at risk of developing the adult respiratory distress syndrome. Am Rev Respir Dis. 1984 Dec;130(6):1058–1064. [PubMed]
  • Ember JA, Sanderson SD, Hugli TE, Morgan EL. Induction of interleukin-8 synthesis from monocytes by human C5a anaphylatoxin. Am J Pathol. 1994 Feb;144(2):393–403. [PMC free article] [PubMed]
  • Fearon DT, Ruddy S, Schur PH, McCabe WR. Activation of the properdin pathway of complement in patients with gram-negative of bacteremia. N Engl J Med. 1975 May 1;292(18):937–940. [PubMed]
  • Fernandez HN, Henson PM, Otani A, Hugli TE. Chemotactic response to human C3a and C5a anaphylatoxins. I. Evaluation of C3a and C5a leukotaxis in vitro and under stimulated in vivo conditions. J Immunol. 1978 Jan;120(1):109–115. [PubMed]
  • Gardinali M, Padalino P, Vesconi S, Calcagno A, Ciappellano S, Conciato L, Chiara O, Agostoni A, Nespoli A. Complement activation and polymorphonuclear neutrophil leukocyte elastase in sepsis. Correlation with severity of disease. Arch Surg. 1992 Oct;127(10):1219–1224. [PubMed]
  • Goldstein IM, Weissmann G. Generation of C5-derived lysosomal enzyme-releasing activity (C5a) by lysates of leukocyte lysosomes. J Immunol. 1974 Nov;113(5):1583–1588. [PubMed]
  • Hack CE, Nuijens JH, Felt-Bersma RJ, Schreuder WO, Eerenberg-Belmer AJ, Paardekooper J, Bronsveld W, Thijs LG. Elevated plasma levels of the anaphylatoxins C3a and C4a are associated with a fatal outcome in sepsis. Am J Med. 1989 Jan;86(1):20–26. [PubMed]
  • Haeffner-Cavaillon N, Cavaillon JM, Laude M, Kazatchkine MD. C3a(C3adesArg) induces production and release of interleukin 1 by cultured human monocytes. J Immunol. 1987 Aug 1;139(3):794–799. [PubMed]
  • Hartmann H, Lübbers B, Casaretto M, Bautsch W, Klos A, Köhl J. Rapid quantification of C3a and C5a using a combination of chromatographic and immunoassay procedures. J Immunol Methods. 1993 Nov 5;166(1):35–44. [PubMed]
  • Haviland DL, McCoy RL, Whitehead WT, Akama H, Molmenti EP, Brown A, Haviland JC, Parks WC, Perlmutter DH, Wetsel RA. Cellular expression of the C5a anaphylatoxin receptor (C5aR): demonstration of C5aR on nonmyeloid cells of the liver and lung. J Immunol. 1995 Feb 15;154(4):1861–1869. [PubMed]
  • Heideman M, Hugli TE. Anaphylatoxin generation in multisystem organ failure. J Trauma. 1984 Dec;24(12):1038–1043. [PubMed]
  • Heideman M, Norder-Hansson B, Bengtson A, Mollnes TE. Terminal complement complexes and anaphylatoxins in septic and ischemic patients. Arch Surg. 1988 Feb;123(2):188–192. [PubMed]
  • Johnson AR, Hugli TE, Müller-Eberhard HJ. Release of histamine from rat mast cells by the complement peptides C3a and C5a. Immunology. 1975 Jun;28(6):1067–1080. [PMC free article] [PubMed]
  • Kreger BE, Craven DE, McCabe WR. Gram-negative bacteremia. IV. Re-evaluation of clinical features and treatment in 612 patients. Am J Med. 1980 Mar;68(3):344–355. [PubMed]
  • Kurimoto Y, de Weck AL, Dahinden CA. Interleukin 3-dependent mediator release in basophils triggered by C5a. J Exp Med. 1989 Aug 1;170(2):467–479. [PMC free article] [PubMed]
  • Langlois PF, Gawryl MS. Accentuated formation of the terminal C5b-9 complement complex in patient plasma precedes development of the adult respiratory distress syndrome. Am Rev Respir Dis. 1988 Aug;138(2):368–375. [PubMed]
  • McCabe WR. Serum complement levels in bacteremia due to gram-negative organisms. N Engl J Med. 1973 Jan 4;288(1):21–23. [PubMed]
  • Mollnes TE, Garred P, Bergseth G. Effect of time, temperature and anticoagulants on in vitro complement activation: consequences for collection and preservation of samples to be examined for complement activation. Clin Exp Immunol. 1988 Sep;73(3):484–488. [PMC free article] [PubMed]
  • Ohlsson K, Björk P, Bergenfeldt M, Hageman R, Thompson RC. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature. 1990 Dec 6;348(6301):550–552. [PubMed]
  • Okusawa S, Dinarello CA, Yancey KB, Endres S, Lawley TJ, Frank MM, Burke JF, Gelfand JA. C5a induction of human interleukin 1. Synergistic effect with endotoxin or interferon-gamma. J Immunol. 1987 Oct 15;139(8):2635–2640. [PubMed]
  • Oppermann M, Götze O. Plasma clearance of the human C5a anaphylatoxin by binding to leucocyte C5a receptors. Immunology. 1994 Aug;82(4):516–521. [PMC free article] [PubMed]
  • Parrillo JE. Pathogenetic mechanisms of septic shock. N Engl J Med. 1993 May 20;328(20):1471–1477. [PubMed]
  • Robbins RA, Russ WD, Rasmussen JK, Clayton MM. Activation of the complement system in the adult respiratory distress syndrome. Am Rev Respir Dis. 1987 Mar;135(3):651–658. [PubMed]
  • Roumen RM, Redl H, Schlag G, Zilow G, Sandtner W, Koller W, Hendriks T, Goris RJ. Inflammatory mediators in relation to the development of multiple organ failure in patients after severe blunt trauma. Crit Care Med. 1995 Mar;23(3):474–480. [PubMed]
  • Sacks T, Moldow CF, Craddock PR, Bowers TK, Jacob HS. Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage. J Clin Invest. 1978 May;61(5):1161–1167. [PMC free article] [PubMed]
  • Scholz W, McClurg MR, Cardenas GJ, Smith M, Noonan DJ, Hugli TE, Morgan EL. C5a-mediated release of interleukin 6 by human monocytes. Clin Immunol Immunopathol. 1990 Nov;57(2):297–307. [PubMed]
  • Smedegård G, Cui LX, Hugli TE. Endotoxin-induced shock in the rat. A role for C5a. Am J Pathol. 1989 Sep;135(3):489–497. [PMC free article] [PubMed]
  • Sprung CL, Schultz DR, Marcial E, Caralis PV, Gelbard MA, Arnold PI, Long WM. Complement activation in septic shock patients. Crit Care Med. 1986 Jun;14(6):525–528. [PubMed]
  • Stevens JH, O'Hanley P, Shapiro JM, Mihm FG, Satoh PS, Collins JA, Raffin TA. Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates. J Clin Invest. 1986 Jun;77(6):1812–1816. [PMC free article] [PubMed]
  • Stöve S, Klos A, Bautsch W, Köhl J. Re-evaluation of the storage conditions for blood samples which are used for determination of complement activation. J Immunol Methods. 1995 May 11;182(1):1–5. [PubMed]
  • Tonnesen MG, Anderson DC, Springer TA, Knedler A, Avdi N, Henson PM. Adherence of neutrophils to cultured human microvascular endothelial cells. Stimulation by chemotactic peptides and lipid mediators and dependence upon the Mac-1, LFA-1, p150,95 glycoprotein family. J Clin Invest. 1989 Feb;83(2):637–646. [PMC free article] [PubMed]
  • Weinberg PF, Matthay MA, Webster RO, Roskos KV, Goldstein IM, Murray JF. Biologically active products of complement and acute lung injury in patients with the sepsis syndrome. Am Rev Respir Dis. 1984 Nov;130(5):791–796. [PubMed]
  • Wenzel RP. The mortality of hospital-acquired bloodstream infections: need for a new vital statistic? Int J Epidemiol. 1988 Mar;17(1):225–227. [PubMed]
  • Zilow G, Joka T, Obertacke U, Rother U, Kirschfink M. Generation of anaphylatoxin C3a in plasma and bronchoalveolar lavage fluid in trauma patients at risk for the adult respiratory distress syndrome. Crit Care Med. 1992 Apr;20(4):468–473. [PubMed]
  • Zilow G, Sturm JA, Rother U, Kirschfink M. Complement activation and the prognostic value of C3a in patients at risk of adult respiratory distress syndrome. Clin Exp Immunol. 1990 Feb;79(2):151–157. [PMC free article] [PubMed]

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