Liu Z, Simpson R J, Cheers C
Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia.
J Immunol. 1994 Jun 1;152(11):5375-80.
We have previously shown that IL-6 is a major cytokine in the serum of mice infected with the intracellular bacterium Listeria monocytogenes, and that injection of rIL-6 before, but not after, infection promotes the recovery of mice from listeriosis. Here we demonstrate that IL-6 is required in the early stages of infection, in that injection of anti-IL-6 Ab 24 or 4 h before infection, but not 24 h after, led to a massive increase in bacterial numbers 4 or more days after infection. On the other hand, injection of rIL-6 before infection significantly suppressed bacterial numbers in the liver and spleen 3 to 4 days after infection and increased the production of IFN-gamma by in vitro cultured CD4+ and CD8+ T cells in response to specific Ag. rIL-6 did not protect SCID mice, which lack both T and B lymphocytes, against Listeria infection. The protective effect of rIL-6 was neutralized by the injection of Ab to IFN-gamma. We conclude that IL-6 plays an essential role in the activation of T cells to produce IFN-gamma, the cytokine that is central to acquired cellular resistance to intracellular bacteria.
我们之前已经表明,白细胞介素-6(IL-6)是感染细胞内细菌单核细胞增生李斯特菌的小鼠血清中的一种主要细胞因子,并且在感染前而非感染后注射重组IL-6(rIL-6)可促进小鼠从李斯特菌病中恢复。在此我们证明,IL-6在感染早期是必需的,因为在感染前24小时或4小时而非感染后24小时注射抗IL-6抗体,会导致感染后4天或更久细菌数量大幅增加。另一方面,在感染前注射rIL-6可显著抑制感染后3至4天肝脏和脾脏中的细菌数量,并增加体外培养的CD4+和CD8+ T细胞针对特异性抗原产生干扰素-γ(IFN-γ)的量。rIL-6不能保护缺乏T和B淋巴细胞的严重联合免疫缺陷(SCID)小鼠免受李斯特菌感染。rIL-6的保护作用可通过注射抗IFN-γ抗体而被中和。我们得出结论,IL-6在激活T细胞产生IFN-γ中起关键作用,IFN-γ是获得性细胞内细菌抗性的核心细胞因子。