Fujioka N, Mukaida N, Harada A, Akiyama M, Kasahara T, Kuno K, Ooi A, Mai M, Matsushima K
Department of Surgery, Cancer Research Institute, Ishikawa, Japan.
J Leukoc Biol. 1995 Jul;58(1):90-8. doi: 10.1002/jlb.58.1.90.
Blocking monoclonal antibodies (mAbs) specific to mouse interleukin-1 receptor antagonist (IL-1ra) were prepared by immunizing Armenian hamsters with recombinant mouse IL-1ra. A sensitive and specific ELISA against mouse IL-1ra was also established. In Propionibacterium acnes-induced liver injury, P. acnes induced transient increase of serum tumor necrosis factor-alpha levels but not those of IL-1ra, IL-1, and IL-6. However, subsequent lipopolysaccharide (LPS) challenge induced the increase of serum levels of all these cytokines and the peak serum IL-1ra level was more than 20 times as high as serum IL-1 levels. Immunohistochemical analysis demonstrated that IL-1ra was predominantly produced by hepatocytes during the course of the priming phase by P. acnes and eliciting phase by LPS challenge. Furthermore, the administration of a mAb to mouse IL-1ra exacerbates the liver injury induced by P. acnes and sublethal dose of LPS, suggesting a protective role of endogenous IL-1ra in this liver injury model.
用重组小鼠白细胞介素 -1 受体拮抗剂（IL -1ra）免疫亚美尼亚仓鼠，制备了针对小鼠 IL -1ra 的阻断性单克隆抗体（mAb）。还建立了一种针对小鼠 IL -1ra 的灵敏且特异的酶联免疫吸附测定（ELISA）。在痤疮丙酸杆菌诱导的肝损伤中，痤疮丙酸杆菌诱导血清肿瘤坏死因子 -α 水平短暂升高，但 IL -1ra、IL -1 和 IL -6 的水平未升高。然而，随后的脂多糖（LPS）刺激诱导了所有这些细胞因子血清水平的升高，且血清 IL -1ra 峰值水平是血清 IL -1 水平的 20 倍以上。免疫组织化学分析表明，在痤疮丙酸杆菌引发阶段和 LPS 刺激激发阶段，IL -1ra 主要由肝细胞产生。此外，给小鼠注射抗 IL -1ra 的 mAb 会加重痤疮丙酸杆菌和亚致死剂量 LPS 诱导的肝损伤，这表明内源性 IL -1ra 在该肝损伤模型中具有保护作用。
