Therapeutic and immunomodulatory effects of glucosamine in combination with low-dose cyclosporine A in a murine model of imiquimod-induced psoriasis

Abstract

Although cyclosporine A (CsA) is a potent immunomodulating agent and is commonly used as a systemic agent for the management of psoriasis patients, current clinical treatments are not always effective due to the clinical inefficacy of low-doses and numerous harmful effects of higher doses. Currently, the combined use of two other systemic drugs often has better therapeutic efficacy and is safer than low or high dose of a single drug. Glucosamine (Glu) also has immunomodulatory properties for autoimmune diseases. The aims of our study were to investigate the therapeutic efficacy of Glu in combination with low-dose CsA on imiquimod (IMQ)-induced psoriasis-like dermatitis in mice and to determine its immunomodulatory mechanism. We found that combined treatment with Glu (300mg/kg) and low-dose (10 or 20mg/kg) CsA strongly ameliorated the development of psoriasis-like skin lesions and reduced the levels of Th1 cytokine (TNF-α) and Th17 cytokines (IL-17, IL-22, and IL-23) in the serum and dorsal skin. Histological findings also showed that the thickening of epidermis, stratum corneum, and inflammatory cell infiltration. Particularly, these combined treatments increased the number of CD4+CD25+ regulatory T (Treg) cells in splenic. These results suggest that use of a combination of each drug might be used as an efficacious and safe alternative therapeutic strategy, as well as may provide an immunomodulatory approach for T cell-mediated autoimmune diseases, including psoriasis.