van der Poll T, Jansen J, Levi M, ten Cate H, ten Cate J W, van Deventer S J
Center of Hemostasis Thrombosis, Atherosclerosis, and Inflammation Research, University of Amsterdam, The Netherlands.
J Exp Med. 1994 Nov 1;180(5):1985-8. doi: 10.1084/jem.180.5.1985.
Interleukin 10 (IL-10) has been shown to inhibit endotoxin-induced tumor necrosis factor (TNF) production. To assess the role of TNF in the induction of IL-10 in endotoxemia, four healthy men were studied after a bolus intravenous injection of recombinant human TNF (50 micrograms/m2). In addition, 13 healthy chimpanzees were investigated after a bolus intravenous injection of Escherichia coli endotoxin (4 ng/kg), 6 animals received endotoxin only, 4 animals received a simultaneous intravenous injection of a monoclonal anti-TNF antibody, whereas 3 chimpanzees were treated with an anti-TNF F(ab')2 fragment 30 min after the administration of endotoxin. TNF induced a modest rise in IL-10 concentrations peaking after 45 min (47 +/- 32 pg/ml; p < 0.05). IL-10 peaked 2 h after injection of endotoxin (202 +/- 61 pg/ml; p < 0.005). In both anti-TNF-treated groups, the early endotoxin-induced TNF activity was completely neutralized. Simultaneous anti-TNF treatment attenuated endotoxin-induced IL-10 release (73 +/- 13 pg/ml; p < 0.01 versus endotoxin alone), whereas postponed anti-TNF treatment did not significantly affect this response (p = 0.21). These results indicate that TNF, in part, mediates the induction of IL-10 in endotoxemia, resulting in an autoregulatory feedback loop.
白细胞介素10（IL-10）已被证明可抑制内毒素诱导的肿瘤坏死因子（TNF）产生。为评估TNF在败血症中诱导IL-10产生的作用，对4名健康男性静脉推注重组人TNF（50微克/平方米）后进行了研究。此外，对13只健康黑猩猩静脉推注大肠杆菌内毒素（4纳克/千克）后进行了研究，6只动物仅接受内毒素，4只动物同时静脉注射单克隆抗TNF抗体，而3只黑猩猩在内毒素给药30分钟后用抗TNF F(ab')2片段进行治疗。TNF诱导IL-10浓度适度升高，在45分钟后达到峰值（47±32皮克/毫升；p<0.05）。内毒素注射后2小时IL-10达到峰值（202±61皮克/毫升；p<0.005）。在两个抗TNF治疗组中，早期内毒素诱导的TNF活性被完全中和。同时进行抗TNF治疗可减弱内毒素诱导的IL-10释放（73±13皮克/毫升；与单独使用内毒素相比，p<0.01），而延迟抗TNF治疗对该反应无显著影响（p=0.21）。这些结果表明，TNF部分介导了败血症中IL-10的诱导，从而形成一个自动调节反馈环。
