Berg D J, Leach M W, Kühn R, Rajewsky K, Müller W, Davidson N J, Rennick D
Department of Immunology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USA.
J Exp Med. 1995 Jul 1;182(1):99-108. doi: 10.1084/jem.182.1.99.
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.
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，我们在白细胞介素-4基因（IL-4T）或白细胞介素-10基因（IL-10T）靶向破坏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小鼠和野生型（wt）小鼠对刺激性巴豆油表现出相同的反应。相比之下，用巴豆油攻击的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物时，发生了不可逆的组织损伤。相比之下，用巴豆油对wt小鼠进行的任何处理导致的组织损伤要少得多，并且炎症消退。中和抗体研究表明，IL-10T小鼠中发生的坏死是由于肿瘤坏死因子的过度产生。用抗肿瘤坏死因子抗体治疗IL-10T小鼠并没有显著降低水肿或炎症细胞的流入，这表明这些变化是由于其他促炎细胞因子的不受控制的产生。还使用接触致敏剂恶唑酮评估了T细胞依赖性免疫反应。IL-4T小鼠的反应与wt小鼠没有差异。相比之下，IL-10T小鼠表现出夸张的CH反应，与wt小鼠相比，其强度和持续时间都增加了。基于这些研究，我们得出结论，IL-10而非IL-4是刺激性反应和CH的天然抑制剂，并且它限制了皮肤中的免疫病理损伤。
