Haskó G, Virág L, Egnaczyk G, Salzman A L, Szabó C
Division of Critical Care Medicine, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Eur J Immunol. 1998 Apr;28(4):1417-25. doi: 10.1002/(SICI)1521-4141(199804)28:04<1417::AID-IMMU1417>3.0.CO;2-L.
Staphylococcal enterotoxin B (SEB), a bacterial superantigen, activates the immune system resulting in a burst of pro- and anti-inflammatory cytokines. A central anti-inflammatory mediator in this process is IL-10. Using IL-10-deficient C57BL/6 (IL-10 KO) mice, we studied the role of endogenous IL-10 in the regulation of the immune response to SEB. SEB (100 microg) induced the release of IL-10 in control C57BL/6 [IL-10 wild type (WT)] mice, but not in their IL-10 KO counterparts. SEB-evoked plasma levels of TNF-alpha, IL-1beta, IL-2, IL-6, IL-12 and IFN-gamma were significantly higher in the IL-10 KO mice than in the WT animals. The release of macrophage inflammatory proteins-1alpha and -2 was also enhanced in the IL-10 KO mice. Further, upon SEB challenge, mice deficient in IL-10 produced higher levels of nitric oxide than the WT animals. IL-10 deficiency resulted in a marked enhancement of the SEB-induced apoptosis of thymocytes. Finally, IL-10 KO mice were more susceptible to SEB-induced lethal shock than their WT controls. These results show that IL-10 plays an important immunoregulatory role in the response to a superantigenic stimulus, by dampening of the shock-inducing inflammatory response and early activation-induced cell death elicited by SEB.
葡萄球菌肠毒素B（SEB）是一种细菌超抗原，可激活免疫系统，导致促炎和抗炎细胞因子的大量释放。这一过程中的一种核心抗炎介质是白细胞介素-10（IL-10）。我们使用IL-10基因敲除的C57BL/6（IL-10 KO）小鼠，研究内源性IL-10在调节对SEB免疫反应中的作用。SEB（100微克）可诱导对照C57BL/6 [IL-10野生型（WT）]小鼠释放IL-10，但在其IL-10 KO同基因小鼠中则不会。在IL-10 KO小鼠中，SEB诱发的血浆肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-2、白细胞介素-6、白细胞介素-12和干扰素-γ水平显著高于野生型动物。巨噬细胞炎性蛋白-1α和-2的释放在IL-10 KO小鼠中也有所增强。此外，在SEB攻击后，IL-10缺陷小鼠产生的一氧化氮水平高于野生型动物。IL-10缺乏导致SEB诱导的胸腺细胞凋亡显著增强。最后，IL-10 KO小鼠比其野生型对照更易受到SEB诱导的致死性休克的影响。这些结果表明，IL-10通过减轻SEB引发的诱导休克的炎症反应和早期激活诱导的细胞死亡，在对超抗原刺激的反应中发挥重要的免疫调节作用。
