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Elevation of IL-18 in Human Sepsis

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Abstract

Interleukin-18 (IL-18) is a recently identified immunoregulatory cytokine that shares biochemical features with IL-1β and acts in part by inducing interferon-gamma (IFN-γ). Endotoxic bacterial lipopolysaccharide (LPS) (1 or 2 ng/kg) was insufficient to increase plasma IL-18 in five healthy adults measured 3, 12, and 24 hr following challenge. In contrast, in the first 96 hr of admission to the surgical intensive care unit, mean maximal serum IL-18 was elevated (1122 ± 259 pg/ml) in nine septic patients compared to six healthy adults (191 ± 42 pg/ml), P < 0.01). Serum IL-18 concentrations in septic patients did not correlate with other measured inflammatory mediators: tumor necrosis factor, IL-6, IL-10, or secretory leukocyte protease inhibitor. Therefore, IL-18 circulates in healthy adults and is a component of the human systemic inflammatory response. Further, stimuli other than LPS may induce IL-18 production in vivo in human sepsis.

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REFERENCES

  1. Gillespie MT, Horwood NJ: Interleukin-18: perspectives on the newest interleukin. Cytokine Growth Factor Rev 9:109-116, 1998

    Google Scholar 

  2. Fantuzzi G, Dinarello CA: Interleukin-18 and interleukin-1 beta: Two cytokine substrates for ICE (caspase-1). J Clin Immunol 19:1-11, 1999

    Google Scholar 

  3. Okamura H, Nagata K, Komatsu T, Tanimoto T, Nukata Y, Tanabe F, Akita K, Torigoe K, Okura T, Fukuda S, Kurimoto M: A novel costimulatory factor for gamma interferon induction found in the livers of mice causes endotoxic shock. Infect Immun 63:3966-3972, 1995

    Google Scholar 

  4. Micallef MJ, Ohtsuki T, Kohno K, Tanabe F, Ushio S, Namba M, Tanimoto T, Torigoe K, Fujii M, Ikeda M, Fukuda S, Kurimoto M: Interferon-gamma-inducing factor enhances T helper 1 cytokine production by stimulated human T cells: Synergism with interleukin-12 for interferon-gamma production. Eur J Immunol 26:1647-1651, 1996

    Google Scholar 

  5. Ohtsuki T, Micallef MJ, Kohno K, Tanimoto T, Ikeda M, Kurimoto M: Interleukin 18 enhances Fas ligand expression and induces apoptosis in Fas-expressing human myelomonocytic KG-1 cells. Anticancer Res 17:3253-3258, 1997

    Google Scholar 

  6. Puren AJ, Razeghi P, Fantuzzi G, Dinarello CA: Interleukin-18 enhances lipopolysaccharide-induced interferon-gamma production in human whole blood cultures. J Infect Dis 178:1830-1834, 1998

    Google Scholar 

  7. Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K, Akita K, Namba M, Tanabe F, Konishi K, Fukuda S, Kurimoto M: Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 378:88-91, 1995

    Google Scholar 

  8. Takeda K, Tsutsui H, Yoshimoto T, Adachi O, Yoshida N, Kishimoto T, Okamura H, Nakanishi K, Akira S: Defective NK cell activity and Th1 response in IL-18-deficient mice. Immunity 8:383-390, 1998

    Google Scholar 

  9. Daemen M, van't Veer C, Wolfs T, Buurman WA: Ischemia/ reperfusion-induced IFN-gamma up-regulation: Involvement of IL-12 and IL-18. J Immunol 162:5506-5510, 1999

    Google Scholar 

  10. van der Poll T, Coyle SM, Barbosa K, Braxton CC, Lowry SF: Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia. J Clin Invest 97:713-719, 1996

    Google Scholar 

  11. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864-874, 1992

    Google Scholar 

  12. Barie PS, Hydo LJ, Fisher E: Prospective comparison of two multiple organ dysfunction/failure scoring systems for prediction of mortality in critical surgical illness. J Trauma 37:660-666, 1994

    Google Scholar 

  13. Grobmyer SR, Barie PS, Nathan CF, Fuortes M, Lin E, Lowry SF, Wright CD, Weyant MJ, Hydo L, Reeves F, Shiloh MU, Ding A: Secretory leukocyte protease inhibitor, an inhibitor of neutrophil activation, is elevated in serum in human sepsis and experimental endotoxemia. Crit Care Med 2000, in press

  14. Taniguchi M, Nagaoka K, Kunikata T, Kayno T, Yamauchi H, Nakamura S, Ikeda M, Orita K, Kurimoto M: Characterization of anti-human interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) monoclonal antibodies and their application in the measurement of human IL-18 by ELISA. J Immunol Methods 206:107-113, 1997

    Google Scholar 

  15. Puren AJ, Fantuzzi G, Dinarello CA: Gene expression, synthesis, and secretion of interleukin 18 and interleukin 1 beta are differentially regulated in human blood mononuclear cells and mouse spleen cells. Proc Natl Acad Sci USA 96:2256-2261, 1999

    Google Scholar 

  16. Roumen RM, Hendriks T, van der Ven-Jongekrijg J, Nieuwenhuijzen GA, Sauerwein RW, van der Meer JW, Goris RJ: Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma. Relation with subsequent adult respiratory distress syndrome and multiple organ failure. Ann Surg 218:769-776, 1993

    Google Scholar 

  17. Guirao X, Lowry SF: Biologic control of injury and inflammation: Much more than too little or too late. World J Surg 20:437-446, 1996

    Google Scholar 

  18. Grobmyer SR, Armstrong RC, Nicholson SC, Gabay C, Arend WP, Potter SH, Melchior M, Fritz LC, Nathan CF: Peptidomimetic fluoromethylketone rescues mice from lethal endotoxic shock. Mol Med 5:585-594, 1999

    Google Scholar 

  19. Novick D, Kim SH, Fantuzzi G, Reznikov LL, Dinarello CA, Rubinstein M: Interleukin-18 binding protein: a novel modulator of the Th1 cytokine response. Immunity 10:127-136, 1999

    Google Scholar 

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Grobmyer, S.R., Lin, E., Lowry, S.F. et al. Elevation of IL-18 in Human Sepsis. J Clin Immunol 20, 212–215 (2000). https://doi.org/10.1023/A:1006641630904

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  • DOI: https://doi.org/10.1023/A:1006641630904

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