Dextromethorphan Exhibits Anti-inflammatory and Immunomodulatory Effects in a Murine Model of Collagen-Induced Arthritis and in Human Rheumatoid Arthritis

Der-Yuan Chen; Chi-Chien Lin; Yi-Ming Chen; Ya-Hsuan Chao; Deng-Ho Yang

doi:10.1038/s41598-017-11378-8

Dextromethorphan Exhibits Anti-inflammatory and Immunomodulatory Effects in a Murine Model of Collagen-Induced Arthritis and in Human Rheumatoid Arthritis

Sci Rep. 2017 Sep 12;7(1):11353. doi: 10.1038/s41598-017-11378-8.

Authors

Der-Yuan Chen^{1

2

3

4}, Chi-Chien Lin^{2

5

6}, Yi-Ming Chen^{1

2

3}, Ya-Hsuan Chao², Deng-Ho Yang^{7

8

9}

Affiliations

¹ Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.
² Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung, Taiwan.
³ Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
⁴ Institute of Microbiology and Immunology, Chung-Shan Medical University, Taichung, Taiwan.
⁵ Department of Biotechnology, Asia University, Taichung, Taiwan.
⁶ Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
⁷ Division of Rheumatology/Immunology/Allergy, Department of Internal Medicine, Taichung Armed Forces General Hospital, Taichung, Taiwan. deng6263@ms71.hinet.net.
⁸ Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan. deng6263@ms71.hinet.net.
⁹ Division of Rheumatology/Immunology/Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. deng6263@ms71.hinet.net.

Abstract

Dextromethorphan (d-3-methoxy-17-methylmorphinan, DXM) is a commonly used antitussive with a favorable safety profile. Previous studies have demonstrated that DXM has anti-inflammatory and immunomodulatory properties; however, the effect of DXM in rheumatoid arthritis (RA) remains unknown. Herein, we found that DXM treatment attenuated arthritis severity and proinflammatory cytokine expression levels, including TNF-α, IL-6, and IL-17A, in paw tissues of CIA mice. DXM treatment also reduced serum TNF-α, IL-6, and IL-17A levels of CIA mice and patients with RA. DXM further decreased the production of anti-CII IgG, IFN-γ, and IL-17A in collagen-reactive CD4⁺ T cells extracted from the lymph nodes of CIA mice. In vitro incubation of bone marrow-derived dendritic cells with DXM limited CD4⁺ T-cell proliferation and inflammatory cytokine secretion. In conclusion, our results showed that DXM attenuated arthritis symptoms in CIA mice and significantly reduced proinflammatory cytokines in patients with RA, suggesting that it can be used as an anti-arthritic agent.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / pharmacology*
Anti-Inflammatory Agents / therapeutic use
Arthritis, Experimental / drug therapy
Arthritis, Experimental / immunology*
Arthritis, Experimental / metabolism
Arthritis, Experimental / pathology*
Arthritis, Rheumatoid / drug therapy
Arthritis, Rheumatoid / immunology*
Arthritis, Rheumatoid / metabolism
Arthritis, Rheumatoid / pathology*
Autoantibodies / blood
Autoantibodies / immunology
Biomarkers
Collagen Type II / immunology
Cytokines / metabolism
Dendritic Cells / immunology
Dendritic Cells / metabolism
Dextromethorphan / pharmacology*
Dextromethorphan / therapeutic use
Disease Models, Animal
Humans
Immunologic Factors / pharmacology*
Immunologic Factors / therapeutic use
Inflammation Mediators / metabolism
Lymphocyte Activation / immunology
Male
Mice
T-Lymphocytes / immunology
T-Lymphocytes / metabolism

Substances

Anti-Inflammatory Agents
Autoantibodies
Biomarkers
Collagen Type II
Cytokines
Immunologic Factors
Inflammation Mediators
Dextromethorphan