IMPAIRED IMMUNE AND ACUTE-PHASE RESPONSES IN INTERLEUKIN-6-DEFICIENT MICE
IMPAIRED IMMUNE AND ACUTE-PHASE RESPONSES IN INTERLEUKIN-6-DEFICIENT MICE
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DOI：
10.1038/368339a0
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发表时间：
1994-03-24
期刊：
影响因子：
64.8
通讯作者：
KOHLER, G
中科院分区：
文献类型：
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作者：
KOPF, M;BAUMANN, H;KOHLER, G
白细胞介素-6（IL-6）是一种多功能细胞因子，调节免疫应答、急性期反应和造血的各个方面（综述见参考文献1、2）。在体外，白血病抑制因子、制瘤素M、睫状神经营养因子和白细胞介素-II显示与IL-6重叠的活性。这种功能冗余可以通过特异性结合受体与共同信号转导受体（gp 130）的相互作用来解释（综述见参考文献3，4）。为了阐明IL-6在体内的独特功能，我们通过同源重组破坏了IL-6基因。IL-6缺陷小鼠发育正常。它们不能有效地控制牛痘病毒和单核细胞增生李斯特菌（一种兼性细胞内细菌）的感染。对水泡性口炎病毒的T细胞依赖性抗体应答受损。此外，组织损伤或感染后的炎症急性期反应严重受损，而脂多糖攻击后仅受到中度影响。我们的结论是，IL-6的产生诱导的损伤或感染是一个重要的在体内SOS信号，协调活动的肝细胞，巨噬细胞和淋巴细胞。
INTERLEUKIN-6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune response, acute-phase reaction and haematopoiesis (for reviews see refs 1, 2). In vitro, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and interleukin-ll display overlapping activities with IL-6. This functional redundancy may be explained by the interactions of specific binding receptors with a common signal-transducing receptor (gp130) (for reviews see refs 3, 4). To elucidate the unique function of IL-6 in vivo, we have disrupted the IL-6 gene by homologous recombination. IL-6-deficient mice develop normally. They fail to control efficiently vaccinia virus and infection with Listeria mono-cytogenes, a facultative intracellular bacterium. The T-cell-dependent antibody response against vesicular stomatitis virus is impaired. Further, the inflammatory acute-phase response after tissue damage or infection is severely compromised, whereas it is only moderately affected after challenge with lipopolysaccharide. We conclude that IL-6 production induced by injury or infection is an important in vivo SOS signal which coordinates activities of liver cells, macrophages and lymphocytes.