Therapeutic effects of intranasal cyclosporine for eosinophilic rhinosinusitis with nasal polyps in a mouse model

Abstract

Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a principally type 2 T helper cell (Th2)-mediated inflammatory disease. Systemic corticosteroids currently represent the most effective treatment for CRSwNP, but their long-term use is constrained due to their detrimental side effects. Long-term use of topical steroids is safe, but their efficacy is often limited. Topical cyclosporine has proven to be safe and effective for Th2-mediated diseases such as allergic conjunctivitis. Objective: It was hypothesized that topical cyclosporine would be an effective novel drug for the treatment of CRSwNP; its therapeutic efficacy was assessed using a previously established mouse model. Methods: After induction of eosinophilic CRSwNP in four-week-old BALB/c mice according to previous protocols, the therapeutic effects of intranasal cyclosporine were evaluated and compared with those of triamcinolone acetonide (TAC). Histopathologic changes were evaluated using hematoxylin and eosin for polyp formation and Sirius red staining for eosinophilic infiltration. The production of cytokines in sinonasal tissues, including tumor necrosis factor (TNF), interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-5, IL-13, and IL-17A, was measured using a cytometric bead array. Results: The number of polyp-like lesions was reduced significantly only by systemic TAC, but the degree of eosinophilic infiltration was decreased significantly by topical cyclosporine, the potency of which was similar to that of topical or systemic TAC. Except for IFN-gamma, the majority of measured cytokines were reduced significantly by topical cyclosporine, although their effects on IL-2 and IL-13 were less potent than those of systemic TAC. Conclusion: Topical cyclosporine might be an effective drug for the management of CRSwNP.