title: Betahistine attenuates murine collagen-induced arthritis by suppressing both inflammatory and Th17 cell responses.
abstract: The objective of this study was to evaluate the potential therapeutic effects of betahistine dihydrochloride (betahistine) in a collagen-induced arthritis (CIA) mouse model. CIA was induced in DBA/1 male mice by primary immunization with 100μl of emulsion containing 2mg/ml chicken type II collagen (CII) mixed with complete Freund's adjuvant (CFA) in an 1:1 ratio, and booster immunization with 100μl of emulsion containing 2mg/ml CII mixed with incomplete Freund's adjuvant (IFA) in an 1:1 ratio. Immunization was performed subcutaneously at the base of the tail. After being boosted on day 21, betahistine (1 and 5mg/kg) was orally administered daily for 2weeks. The severity of CIA was determined by arthritic scores and assessment of histopathological joint destruction. Expression of cytokines in the paw and anti-CII antibodies in the serum was evaluated by ELISA. The proliferative response against CII in the lymph node cells was measured by (3)H-thymidine incorporation assay. The frequencies of different CII specific CD4(+) T cell subsets in the lymph node were determined by flow-cytometric analysis. Betahistine treatment attenuated the severity of arthritis and reduced the levels of pro-inflammatory cytokines, including TNF-α, IL-6, IL-23 and IL-17A, in the paw tissues of CIA mice. Lymph node cells from betahistine-treated mice showed a decrease in proliferation, as well as a lower frequency of Th17 cells. In vitro, betahistine suppressed CD4(+) T cell differentiation into Th17 cells. These results indicate that betahistine is effective in suppressing both inflammatory and Th17 responses in mouse CIA and that it may have therapeutic value as an adjunct treatment for rheumatoid arthritis.
authors: Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors: Kuo-Tung
authors: KT
authors: Tang
authors: Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan.
authors: Ya-Hsuan
authors: YH
authors: Chao
authors: Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors: Der-Yuan
authors: DY
authors: Chen
authors: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan; Department of Emergency, Toxicology Center, China Medical University Hospital, Taichung, Taiwan.
authors: Yun-Ping
authors: YP
authors: Lim
authors: Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors: Yi-Ming
authors: YM
authors: Chen
authors: Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan.
authors: Yi-Rong
authors: YR
authors: Li
authors: Division of Rheumatology/Immunology/Allergy, Department of Internal Medicine, Taichung Armed Forces General Hospital, Taichung, Taiwan.
authors: Deng-Ho
authors: DH
authors: Yang
authors: Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan; Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. Electronic address: lincc@dragon.nchu.edu.tw.
authors: Chi-Chen
authors: CC
authors: Lin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000906:Antibodies / Q000097:blood; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001621:Betahistine / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology; D016207:Cytokines / Q000097:blood; D006801:Humans; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D024043:Collagen Type II; D016207:Cytokines; D001621:Betahistine
keywords: Arthritis; Betahistine; Differentiation; RORγt; Th17