Shornick L P, De Togni P, Mariathasan S, Goellner J, Strauss-Schoenberger J, Karr R W, Ferguson T A, Chaplin D D
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Exp Med. 1996 Apr 1;183(4):1427-36. doi: 10.1084/jem.183.4.1427.
Mice rendered deficient in IL-1 beta by gene targeting in embryonic stem cells develop and grow normally in a protected laboratory environment. Endotoxin-stimulated peritoneal macrophages from IL-1beta-deficient mice showed normal synthesis and cellular release of IL-1alpha after treatment with 5 mM ATP demonstrating that IL-1beta is not necessary for expression and release of the IL-1alpha isoform. Mice deficient in IL-1beta showed unaltered sensitivity to endotoxic shock, with or without pretreatment with D-galactosamine. In contrast, IL-1beta-deficient mice showed defective contact hypersensitivity responses to topically applied trinitrochlorobenzene (TNCB). This defect could be overcome either by application of very high doses of sensitizing antigen, or by local intradermal injection of recombinant IL-1beta immediately before antigen application. These data demonstrate an essential role for IL-1beta in contact hypersensitivity and suggest that IL-1beta acts early during the sensitization phase of response. They suggest an important role for IL-1beta in initiation of the host of response at the epidermal barrier.
通过胚胎干细胞基因靶向使白细胞介素-1β（IL-1β）功能缺失的小鼠，在受保护的实验室环境中发育和生长正常。来自IL-1β缺陷小鼠的内毒素刺激的腹腔巨噬细胞在用5 mM三磷酸腺苷（ATP）处理后，显示出白细胞介素-1α（IL-1α）的正常合成和细胞释放，这表明IL-1β对于IL-1α同工型的表达和释放不是必需的。IL-1β缺陷的小鼠对内毒素休克的敏感性未改变，无论是否用D-半乳糖胺预处理。相反，IL-1β缺陷的小鼠对局部应用的三硝基氯苯（TNCB）表现出有缺陷的接触性超敏反应。通过应用非常高剂量的致敏抗原，或在抗原应用前立即局部皮内注射重组IL-1β，可以克服这种缺陷。这些数据证明了IL-1β在接触性超敏反应中的重要作用，并表明IL-1β在反应的致敏阶段早期起作用。它们表明IL-1β在表皮屏障处启动宿主反应中起重要作用。
