Dextromethorphan Exhibits Anti-Inflammatory and Immunomodulatory Effects in a Murine Model: Therapeutic Implication in Psoriasis

Abstract

Psoriasis is an immune-mediated skin disease with a worldwide prevalence of 2–4% that causes scaling erythematous skin lesions. It is a chronic relapsing and complex multifactorial disease that often necessitates long-term therapy. Despite various novel therapies, psoriasis remains a treatable but non-curable disease. Because the antitussive medication dextromethorphan (DXM) can inhibit murine bone marrow and human monocytes and slow the progression of arthritis in mice with type II collagen-induced arthritis, we explored whether the oral administration of DXM to mice with imiquimod (IMQ)-induced psoriasis can effectively alleviate psoriasis symptoms and improve immune regulation. Herein, we examined the therapeutic effects of DXM on psoriasis and its potential mechanisms of action in an IMQ-induced psoriasis mice model. We found that an oral dose of DXM (10 mg/kg) could more significantly reduce psoriasis symptoms compared with intraperitoneal injection. Seven days after the oral administration of DXM, the Psoriasis Area and Severity Index (PASI) score was significantly decreased compared with that in the vehicle group. Furthermore, DXM treatment also significantly ameliorated the psoriasis symptoms and the histopathological features of psoriasis, including stratum corneum thickening, desquamation, and immune cell infiltration. Additionally, DXM reduced the mRNA levels of the cytokines TNF-α, IL-6, IL-17A, and IL-22 in skin and the percentage of IL-17A and IL-22 producing T cell receptor γδ T cells (TCRγδT). Taken together, our research demonstrated that DXM could inhibit keratinocyte proliferation and alleviate psoriasis symptoms, which suggests the potential application of DXM in the treatment of chronic inflammation and autoimmune diseases.

The N-Methyl-D-Aspartate Receptor Antagonist Dextromethorphan Improves Glucose Homeostasis and Preserves Pancreatic Islets in NOD Mice

“…For example, DXM treatment inhibits lipopolysaccharide (LPS)-induced functional maturation of murine and human dendritic cells (DC), reduces their production of proinflammatory cytokines, chemokines and oxidative stress, and impairs the ability of LPS-induced murine DCs to activate antigen-specific T-cell responses 34 36 . In murine models of chronic immune-mediated inflammatory disorders, DXM was shown to slow disease progression and alleviate symptoms by decreasing the generation of proinflammatory cytokines 36 38 . In human individuals with autoimmune rheumatoid arthritis, treatment with DXM as add-on to disease-modifying-antirheumatic drugs significantly reduced circulating levels of proinflammatory cytokines, including TNFα and IL-6 36 .…”