Cytokine Measurements in Septic Shock (1993)

Editorials15 October 1993Cytokine Measurements in Septic ShockCharles A. Dinarello, MD and Joseph G. Cannon, PhDCharles A. Dinarello, MDTufts University and New England Medical Center, Boston, MA 02111. and Joseph G. Cannon, PhDTufts University and New England Medical Center, Boston, MA 02111.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-8-199310150-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF) affect nearly every cell type by increasing the production of substances that promote local and systemic inflammatory processes. These include the up-regulation of the genes for cyclooxygenase and nitric oxide synthases, the release of platelet-activating factor, and the synthesis of endothelial adhesion molecules. Vasodilation, reduced tissue oxidation, and leukocyte-mediated necrosis are thought to contribute to organ failure and death in patients with septic shock. Although IL-1 and TNF are capable of inducing shock individually, of greater biological relevance is the synergistic action of these two cytokines.In animal models of disease, ...References1. Knudsen PJ, Dinarello CA, Strom TB. Glucocorticoids inhibit transcriptional and post-transcriptional expression of interleukin 1 in U937 cells. J Immunol. 1987; 139:4129-34. Google Scholar2. Ohlsson K, Bjork P, Bergenfeldt M, Hageman R, Thompson RC. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature. 1990; 348:550-2. Google Scholar3. Fischer E, Marano MA, Van Zee KJ, Rock CS, Hawes AS, Thompson WA, et al. Interleukin-1 receptor blockade improves survival and hemodynamic performance in Escherichia coli septic shock, but fails to alter host responses to sublethal endotoxemia. J Clin Invest. 1992; 89:1551-7. 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Plasma cytokines and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med. 1993; 119:771-8. Google Scholar9. Fisher CJ Jr, Opal SM, Dhainaut JF, Stephens S, Zimmerman JL, Nightingale P, et al. Influence of an anti-tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis. Crit Care Med. 1993; 21:318-27. Google Scholar10. Gershenwald JE, Fong YM, Fahey TJ 3d, Calvano SE, Chizzonite R, Kilian PL, et al. Interleukin 1 receptor blockade attenuates the host inflammatory response. Proc Natl Acad Sci USA. 1990; 87:4966-70. Google Scholar11. Fong Y, Tracey KJ, Moldawer LL, Hesse DG, Manogue KB, Kenney JS, et al. Antibodies to cachectin/tumor necrosis factor reduce interleukin 1 and interleukin 6 appearance during lethal bacteremia. J Exp Med. 1989; 170:1627-33. Google Scholar12. Granowitz EV, Vannier E, Poutsiaka DD, Dinarello CA. 1992. Effect of interleukin-1 (IL-1) blockade on cytokine synthesis: II. Interleukin-1 receptor antagonist inhibits lipopolysaccharide-induced cytokine synthesis by human monocytes. Blood. 1992; 79:2364-9. Google Scholar13. Fisher CJ Jr, Dhainaut JF, Pribble J, Knaus W, Catalano MA. A study evaluating the efficacy of human recombinant interleukin-1 receptor antagonist in the treatment of patients with sepsis syndrome: preliminary results from a Phase III multicenter trial (Abstract). 13th International Symposium on Intensive Care and Emergency Medicine, Brussels, Belgium. New York: Springer-Verlag. Google Scholar14. Cannon JG, van der Meer JW, Kwiatkowski D, Endres S, Lonnemann G, Burke JF, et al. Interleukin-1 in human plasma: optimization of blood collection, plasma extraction, and radioimmunoassay methods. Lymphokine Res. 1988; 7:457-67. Google Scholar15. Wogensen L, Jensen M, Svensson P, Worsaae H, Welinder B, Nerup J. Pancreatic -cell function and interleukin-1b in plasma during the acute phase response in patients with major burn injuries. Eur J Immunol. 1993; (In press). Google Scholar16. Cannon JG, Nerad JL, Poutsiaka DD, Dinarello CA. Measuring circulating cytokines. J Appl Physiol. 1993; (In press). Google Scholar17. Cannon JG, Tompkins RG, Gelfand JA, Michie HR, Stanford GG, van der Meer JW, et al. Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J Infect Dis. 1990; 161:79-84. Google Scholar18. Munoz C, Carlet J, Fitting C, Misset B, Bleriot JP, Cavaillon JM. Dysregulation of in vitro cytokine production of monocytes during sepsis. J Clin Invest. 1991; 88:1747-54. Google Scholar19. Dinarello CA. ELISA kits based on monoclonal antibodies do not measure total IL-1 synthesis. J Immunol Methods. 1992; 148:255-9. Google Scholar20. van der Meer JW, Barza M, Wolff SM, Dinarello CA. A low dose of recombinant interleukin 1 protects granulocytopenic mice from lethal gram-negative infection. Proc Natl Acad Sci USA. 1988; 85: 1620-3. Google Scholar Author, Article, and Disclosure InformationAffiliations: Tufts University and New England Medical Center, Boston, MA 02111.Corresponding Author: Charles A. Dinarello, MD, Division of Geographic Medicine and Infectious Diseases, New England Medical Center Hospitals, 750 Washington Street, Box 68, Boston, MA 02111.Grant Support: In part by NIH grants AI15614, AI33414, and AR39595. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPlasma Cytokine and Endotoxin Levels Correlate with Survival in Patients with the Sepsis Syndrome Larry C. Casey , Robert A. Balk , and Roger C. 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