Höpken U, Mohr M, Strüber A, Montz H, Burchardi H, Götze O, Oppermann M
Department of Immunology, University of Göttingen, Germany.
Eur J Immunol. 1996 May;26(5):1103-9. doi: 10.1002/eji.1830260522.
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.
补体激活片段C5a最近被证明可诱导外周血单核细胞合成白细胞介素（IL）-6。为了更好地理解C5a在体内细胞因子调节中的作用，我们在脓毒性休克动物模型中研究了用眼镜蛇毒因子（CVF）补体耗竭或抗C5a单克隆抗体（mAb）对IL-6生成的影响。随后用大肠杆菌攻击的补体耗竭猪在6小时观察期内产生的IL-6明显（p<0.05）少于补体充足的对照组。为了具体研究C5a在IL-6调节中的作用，我们制备了一种可中和猪C5a生物活性的C5a（57-74）肽特异性mAb（T13/9）。mAb T13/9与前体蛋白C5无交叉反应。在诱导败血症之前用抗C5a mAb T13/9预处理猪，与对照动物相比，血清IL-6生物活性降低了75%以上（p<0.0001）。这些结果表明C5a在革兰氏阴性菌血症中IL-6合成的调节中起作用。
