Inoue A, Koh C S, Yamazaki M, Yahikozawa H, Ichikawa M, Yagita H, Kim B S
Third Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
J Immunol. 1998 Nov 15;161(10):5586-93.
We examined the role of IL-12, a cytokine critical to the evolution of cellular responses, in the development of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Treatment with mAbs to IL-12, especially during the effector phase, resulted in significant suppression of the development of this disease both clinically and histologically. In mice treated with these mAbs, the production of inflammatory and Th1-derived cytokines such as TNF-alpha and IFN-gamma in the spleen cells was decreased, and that of Th2-derived cytokines such as IL-4 and IL-10 was increased. The delayed type hypersensitivity and T cell proliferative response specific for TMEV were decreased by this treatment. These data suggest that IL-12 is critically involved in the pathogenesis of TMEV-IDD and that Abs to IL-12 could be a novel therapeutic approach in the clinical treatment of demyelinating diseases such as human multiple sclerosis.
我们研究了白细胞介素-12（IL-12）在泰勒氏鼠脑脊髓炎病毒诱导的脱髓鞘疾病（TMEV-IDD）发展过程中的作用，IL-12是一种对细胞反应演变至关重要的细胞因子。用抗IL-12单克隆抗体治疗，尤其是在效应阶段进行治疗，在临床和组织学上均导致该疾病的发展受到显著抑制。在用这些单克隆抗体治疗的小鼠中，脾细胞中炎性细胞因子和Th1衍生细胞因子（如肿瘤坏死因子-α和干扰素-γ）的产生减少，而Th2衍生细胞因子（如白细胞介素-4和白细胞介素-10）的产生增加。这种治疗降低了针对TMEV的迟发型超敏反应和T细胞增殖反应。这些数据表明，IL-12在TMEV-IDD的发病机制中起关键作用，抗IL-12抗体可能是临床治疗人类多发性硬化症等脱髓鞘疾病的一种新的治疗方法。
