Interleukin 10 but not interleukin 4 is a natural suppressant of cutaneous inflammatory responses.
Interleukin 10 but not interleukin 4 is a natural suppressant of cutaneous inflammatory responses.
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DOI：
10.1084/jem.182.1.99
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发表时间：
1995-07-01
期刊：
影响因子：
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通讯作者：
Rennick D
中科院分区：
文献类型：
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作者：
Berg DJ;Leach MW;Kühn R;Rajewsky K;Müller W;Davidson NJ;Rennick D
我们研究了内源性产生的白细胞介素（IL） 4和IL-10在皮肤炎症和免疫反应调节中的作用。在这些实验中，在靶向破坏IL-4 （IL-4T）或IL-10 （IL-10T）基因的小鼠中引发了刺激性和接触性超敏反应（CH）。我们的研究表明，IL-4T和野生型（wt）小鼠对刺激性巴豆油表现出相同的反应。相反，巴豆油刺激IL-10T小鼠的反应异常增强。当IL-10T小鼠暴露于更高剂量的刺激时，发生不可逆的组织损伤。相比之下，任何用巴豆油治疗的小白鼠导致的组织损伤和炎症的消退都要小得多。中和抗体研究表明，IL-10T小鼠发生的坏死是由于肿瘤坏死因子的过量产生。IL-10T小鼠的抗肿瘤坏死因子抗体治疗并没有显著减少水肿或炎症细胞的涌入，提示这些变化是由于其他促炎细胞因子的不受控制的产生。T细胞依赖性免疫反应也被评估使用接触敏化剂恶唑酮。IL-4T小鼠的反应与wt小鼠没有差异。相比之下，与wt小鼠相比，IL-10T小鼠表现出夸张的CH反应，在强度和持续时间上都有所增加。基于这些研究，我们得出结论，IL-10，而不是IL-4，是刺激反应和CH的天然抑制剂，它限制了皮肤的免疫病理损伤。
We have examined the role of endogenously produced interleukin (IL) 4 and IL-10 in the regulation of inflammatory and immune reactions in the skin. In these experiments, irritant and contact hypersensitivity (CH) responses were elicited in mice with targeted disruptions of the IL-4 (IL-4T) or IL-10 (IL-10T) gene. Our study showed that IL-4T and wild- type (wt) mice exhibited equivalent responses to the irritant croton oil. In contrast, the response of IL-10T mice challenged with croton oil was abnormally increased. When IL-10T mice were exposed to a higher dose of irritant, irreversible tissue damage occurred. By comparison, any treatment of wt mice with croton oil resulted in far less tissue damage and resolution of inflammation. Neutralizing antibody studies demonstrated that the necrosis that occurred in IL-10T mice was due to the overproduction of tumor necrosis factor. The anti-tumor necrosis factor antibody treatment of IL-10T mice did not significantly reduce the edema or the influx of inflammatory cells, suggesting that these changes were due to the uncontrolled production of other proinflammatory cytokines. T cell-dependent immune responses were also evaluated using the contact sensitizer oxazolone. The response of IL-4T mice did not differ from wt mice. In contrast, IL-10T mice mounted an exaggerated CH response, increased in both magnitude and duration as compared with wt mice. Based on these studies, we have concluded that IL-10, but not IL-4, is a natural suppressant of irritant responses and of CH, and it limits immunopathologic damage in the skin.