Rifampicin attenuates experimental autoimmune encephalomyelitis by inhibiting pathogenic Th17 cells responses

• Published in: Journal of neurochemistry 2016-12, Vol.139 (6), p.1151-1162
• Main Authors: Ma, Ke, Chen, Xi, Chen, Jia‐Cheng, Wang, Ying, Zhang, Xi‐meng, Huang, Fan, Zheng, Jun‐Jiong, Chen, Xiong, Yu, Wei, Cheng, Ke‐Ling, Feng, Yan‐Qing, Gu, Huai‐yu
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antibiotics; Autoimmune diseases; Dose-Response Relationship, Drug; Encephalitis; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - immunology; experimental autoimmune encephalomyelitis; Female; JAK/STAT signal pathway; Mice; Mice, Inbred C57BL; Multiple sclerosis; Neurochemistry; Original; ORIGINAL ARTICLES; Pharmacology; Random Allocation; rifampicin; Rifampin - pharmacology; Rifampin - therapeutic use; Th17 cell; Th17 Cells - drug effects; Th17 Cells - immunology
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.13871

Rifampicin, a broad‐spectrum antibiotic, has neuroprotective, immunosuppressive, and anti‐inflammatory properties. However, the effect of rifampicin on autoimmune disorders of the nervous system is not clear. In this study, we investigated whether rifampicin was beneficial to myelin oligodendrocyte glycoprotein peptide (MOG33–35)‐induced female C57BL/6 experimental autoimmune encephalomyelitis (EAE) mice, the well‐established animal model of multiple sclerosis. Rifampicin treatment (daily from the first day after EAE immunization) remarkably attenuated clinical signs and loss of body weight, which are associated with suppression of inflammatory infiltration and demyelination in spinal cords of EAE mice. Furthermore, rifampicin dramatically reduced the disruption of blood–brain barrier integrity, down‐regulated serum concentration of IL‐6 and IL‐17A, inhibited pathological Th17 cell differentiation, and modulated the expression of p‐STAT3 and p‐p65. These results suggest that rifampicin is effective for attenuating the clinical severity of EAE mice, which may be related to its inhibitive ability in differentiation of Th17 cell and secretion of its key effector molecule IL‐17A via regulation of excessive activation of the key signaling molecules of JAK/STAT pathway. Our findings may be helpful for developing therapeutic and preventive strategies for multiple sclerosis. Rifampicin, a broad‐spectrum antibiotic, has neuroprotective, immunosuppressive, and anti‐inflammatory properties. However, the effect of rifampicin on autoimmune disorders of the nervous system is not clear. In this study, we investigated whether rifampicin was beneficial to myelin oligodendrocyte glycoprotein peptide (MOG33–35)‐induced experimental autoimmune encephalomyelitis (EAE) mice, the well‐established animal model of multiple sclerosis (MS). We discovered that rifampicin is effective for attenuating the clinical severity of EAE. Our findings may be helpful for developing the therapeutic and preventive strategies for MS.