IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis

• DOI: 10.1073/pnas.0802218105
• Publication Date: 2008-06-25T02:38:38Z
• Authors: Satoshi Serada; Minoru Fujimoto; Masahiko Mihara; Nobuo Koike; Yoshiyuki Ohsugi; Shintaro Nomura; Hiroto Yoshida; Teppei Nishikawa; Fumitaka Terabe; Tomoharu Ohkawara; Tsuyoshi Takahashi; Barry Ripley; Akihiro Kimura; Tadamitsu Kishimoto; Tetsuji Naka
• Keywords: Central Nervous System; Encephalomyelitis, Autoimmune, Experimental; Interleukin-6; Lymphoid Tissue; Antibodies, Monoclonal; T-Lymphocytes, Helper-Inducer; Th1 Cells; Lymphocyte Activation; 3. Good health; Mice, Inbred C57BL; Epitopes; Mice; Myelin-Associated Glycoprotein; 03 medical and health sciences; 0302 clinical medicine; Cell Movement; Animals; Myelin-Oligodendrocyte Glycoprotein; Antigens; Peptides; Myelin Proteins; Myelin Sheath

The development of Th17 cells is a key event in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine model of human multiple sclerosis (MS). Previous studies have demonstrated that an IL-6-dependent pathway is involved in the differentiation of Th17 cells from naïve CD4-positive T cellsin vitro. However, the role of IL-6in vivoin the development of Th17 cells in EAE has remained unclear. In the present study, we found that IL-6 blockade by treatment with an anti-IL-6 receptor monoclonal antibody (anti-IL-6R mAb) inhibited the development of EAE and inhibited the induction of myelin oligodendrocyte glycoprotein (MOG) peptide-specific CD4-positive, CD8-positive, and Th17 T cells, in inguinal lymph nodes. Thus, the protective effect of IL-6 blockade in EAE is likely to be mediated via the inhibition of the development of MOG-peptide-specific Th17 cells and Th1 cells, which in turn leads to reduced infiltration of T cells into the CNS. These findings indicate that anti-IL-6R mAb treatment might represent a novel therapy for human MS.