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Inhibition of interleukin-6 synthesis in an animal model of septic shock by anti-C5a monoclonal antibodies

Item Type:Article
Title:Inhibition of interleukin-6 synthesis in an animal model of septic shock by anti-C5a monoclonal antibodies
Creators Name:Hoepken, U. and Mohr, M. and Strueber, A. and Montz, H. and Burchardi, H. and Goetze, O. and Oppermann, M.
Abstract:The complement activation fragment C5a was recently shown to induce interleukin (IL)-6 synthesis by peripheral blood mononuclear cells. To understand better the role of C5a in cytokine regulation in vivo, we investigated the effects of complement depletion by cobra venom factor (CVF) or of anti-C5a monoclonal antibodies (mAb) on IL-6 generation in an animal model of septic shock. Complement-depleted pigs which were subsequently challenged with Escherichia coli generated significantly (p < 0.05) less IL-6 during the 6-h observation period than complement-sufficient controls. To address specifically the role of C5a in IL-6 regulation, we produced a C5a(57-74) peptide-specific mAb (T13/9) which neutralizes the bioactivity of porcine C5a. The mAb T13/9 does not cross-react with the precursor protein C5. The pretreatment of pigs with anti-C5a mAb T13/9 prior to the induction of sepsis resulted in a decrease of over 75% in serum IL-6 bioactivity compared to control animals (p < 0.0001). These results indicate a role for C5a in the modulation of IL-6 synthesis in Gram-negative bacteremia.
Keywords:C5a, Interleukin-6, Sepsis, Animals, Mice, Swine
Source:European Journal of Immunology
ISSN:0014-2980
Publisher:Wiley (U.S.A.)
Volume:26
Number:5
Page Range:1103-1109
Date:May 1996
Official Publication:https://doi.org/10.1002/eji.1830260522
PubMed:View item in PubMed

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