Smith S R, Terminelli C, Denhardt G, Narula S, Thorbecke G J
Department of Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
Cell Immunol. 1996 Nov 1;173(2):207-14. doi: 10.1006/cimm.1996.0269.
Several laboratories have described the protective effects of interleukin-10 (IL-10) in mouse models of lethal endotoxemia. In most of these experiments, protection was observed in normal mice that were given a lethal dose of LPS. However, we failed to observe protection with IL-10 in LPS-challenged mice that had been primed with Corynebacterium parvum (Proprionibacterium acnes). We have extended our studies with IL-10 in C. parvum-primed mice and in some cases have observed protection that appears to depend on the strength of the sensitization to C. parvum. When IL-10 was administered to mice at the time of priming, it was particularly effective in blocking sensitization, as evidenced by the inability of treated mice to mount a strong inflammatory cytokine response when subsequently challenged with LPS. Following such treatment with IL-10, C. parvum-primed mice were also protected from a subsequent lethal challenge with rMuTNF-alpha. In addition, the mice were protected against LPS- and TNF-alpha-induced lethality with a single dose of an anti-TNF-alpha or anti-IFN-gamma mAb given at the time of priming. Our results suggest that TNF-alpha and IFN-gamma are produced early after priming with C. parvum and are at least partly responsible for the enhanced sensitivity of the mice to LPS and TNF-alpha. IL-10 affords protection to the mice because of its ability to block the C. parvum-induced TNF-alpha and IFN-gamma responses.
几个实验室已经描述了白细胞介素-10（IL-10）在致死性内毒素血症小鼠模型中的保护作用。在大多数这些实验中，在给予致死剂量LPS的正常小鼠中观察到了保护作用。然而，我们在经短小棒状杆菌（痤疮丙酸杆菌）致敏的LPS攻击小鼠中未观察到IL-10的保护作用。我们在经短小棒状杆菌致敏的小鼠中扩展了对IL-10的研究，在某些情况下观察到了似乎取决于对短小棒状杆菌致敏强度的保护作用。当在致敏时给小鼠施用IL-10时，它在阻断致敏方面特别有效，这表现为经处理的小鼠在随后受到LPS攻击时无法产生强烈的炎性细胞因子反应。用IL-10进行这样的处理后，经短小棒状杆菌致敏的小鼠也受到保护，免受随后rMuTNF-α的致死性攻击。此外，在致敏时给予单剂量的抗TNF-α或抗IFN-γ单克隆抗体，小鼠可免受LPS和TNF-α诱导的致死性。我们的结果表明，TNF-α和IFN-γ在经短小棒状杆菌致敏后早期产生，并且至少部分地导致小鼠对LPS和TNF-α的敏感性增强。IL-10由于其阻断短小棒状杆菌诱导的TNF-α和IFN-γ反应的能力而给予小鼠保护。
