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Suppressive Effect on Theiler’s Murine Encephalomyelitis Virus-Induced Demyelinating Disease by the Administration of Anti-IL-12 Antibody

Atsushi Inoue^*, Chang-Sung Koh^2,*, Masashi Yamazaki^*, Hiroyuki Yahikozawa^*, Motoki Ichikawa, Hideo Yagita and Byung S. Kim^§

^* Third Department of Medicine and Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan; Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan; and ^§ Departments of Microbiology-Immunology and Pathology, Northwestern University Medical School, Chicago, IL 60611

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- and IFN- 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.

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