Contribution of interleukin 17A to the development and regulation of allergic inflammation in a murine allergic rhinitis model

Abstract

Background: Interleukin (IL) 17A, a key cytokine of T(H)17 cells, is a well-known proinflammatory cytokine. Despite the important role of T(H)17 cells in acute airway inflammation, the role of IL-17A in allergic rhinitis (AR) remains unclear.

Objective: To investigate the role of IL-17A in the allergic response in AR.

Methods: Wild-type BALB/c and IL-17A-deficient mice were immunized intraperitoneally and were challenged intranasally with ovalbumin. Allergic symptom scores, eosinophil infiltration, serum IgE level, and the levels of several cytokines in nasal lavage fluid and splenocyte supernatants were analyzed.

Results: IL-17A levels increased significantly more in ovalbumin-sensitized wild-type mice than in the negative control group. IL-17A-deficient mice showed a significant decrease in allergic symptoms, serum IgE levels, and eosinophil infiltration into the nasal mucosa compared with wild-type mice. IL-17A-deficient mice also showed decreased histamine and cysteinyl leukotriene release. Bone marrow-derived mast cells from IL-17A-deficient mice showed significantly lower degranulation and secretion of tumor necrosis factor α. Moreover, IL-17A deficiency attenuated the IL-5 level in nasal lavage fluid and its production in response to ovalbumin but did not increase interferon γ production and its level in nasal lavage fluid. In addition, secretion of IL-17A from spleen cells induced the expression of proinflammatory cytokine messenger RNA in macrophages. The mean level of proinflammatory cytokines, including tumor necrosis factor α and IL-17, decreased in IL-17A-deficient mice.

Conclusion: These results suggest that IL-17A may partly contribute to the development of nasal allergic inflammation in an AR animal model and regulate AR via the activation of proinflammatory cytokines and modulation of T(H)2 cytokine.