Title: Interferon gamma, a mediator of lethal lipopolysaccharide-induced Shwartzman-like shock reactions in mice
Authors: Heremans, Hubertine ×
Van Damme, Jozef
Dillen, C
Dijkmans, R
Billiau, Alfons #
Issue Date: Jun-1990
Series Title: Journal of Experimental Medicine vol:171 issue:6 pages:1853-69
Abstract: The involvement of cytokines in the pathogenesis of a generalized, Shwartzman-like lethal inflammatory response to bacterial lipopolysaccharides (LPS) was studied by testing the ability of cytokines or neutralizing anticytokine antibodies to modify the course of the syndrome. The reaction was elicitable in non-SPF NMRI mice by two consecutive injections of S. marcescens LPS: a first injection in the footpad, followed after 24 h by an intravenous dose; the size and route of the preparatory LPS dose were found to be critical. Treatment with mAbs against IFN-gamma was found to completely prevent the reaction. Treatment with IFN-gamma on the other hand, rendered the mice more sensitive to elicitation of the reaction. In contrast, systemic administration of IFN-alpha/beta exerted a desensitizing effect. The role of endogenous cytokines in the pathogenesis of this generalized Shwartzman reaction was also documented by a study of the cytokine levels in the serum of the mice. In comparisons between mice given lethal and nonlethal induction schedules, a good correlation was found between mortality rates and height of IFN or TNF levels, but no correlation was seen with IL-6 levels. Also, in mice that were protected by anti-IFN-gamma antibody, serum IFN and TNF were undetectable, whereas IL-6 levels were as high as in unprotected mice. These data provide evidence that among the cytokines that govern the inflammatory response to LPS, endogenous IFN-gamma occupies a key position. These findings therefore also open perspectives for clinical application of IFN-gamma antagonists.
ISSN: 0022-1007
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Academic Center for General Practice
Laboratory of Molecular Immunology (Rega Institute)
Laboratory of Immunobiology (Rega Institute)
× corresponding author
# (joint) last author

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