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.
Highlights
Dextromethorphan (d-3-methoxy-17-methylmorphinan, DXM) is a commonly used antitussive with a favorable safety profile
DXM further decreased the production of anti-collagen type II (CII) IgG, IFN-γ, and IL-17A in collagen-reactive CD4+ T cells extracted from the lymph nodes of CIA mice
To the best of our knowledge, this study is the first attempt to demonstrate that DXM was effective in preventing CIA in mice, as evidenced by a decrease in paw swelling and significant reduction in histological synovitis in mice administered an intradermal injection of DXM
Summary
Dextromethorphan (d-3-methoxy-17-methylmorphinan, DXM) is a commonly used antitussive with a favorable safety profile. 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 reduced serum TNF-α, IL-6, and IL-17A levels of CIA mice and patients with RA. 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. DXM reduced the production of pro-inflammatory factors (such as TNF-α) from activated microglia or macrophages in the brain and aortic sinuses[15,16,17] as well as the levels of group A streptococcal (GAS)-induced pro-inflammatory cytokines and chemokines in a mouse model[18]. The aims of the present study were as follows: (1) to evaluate the therapeutic effects of DXM in a murine RA model (collagen-induced arthritis, CIA) and in patients with RA, and (2) to explore the possible molecular mechanisms underlying the therapeutic effects of DXM
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