Background: Allergic rhinitis is one of the most common allergic inflammatory diseases characterized by a predominant T H2 response with antigen-specific IgE synthesis. IL-15 plays important roles in activation and maintenance of memory CD8 +T cells capable of producing IFN-γ, which regulates T H2 responses. Objective: To investigate the roles of endogenous IL-15 in allergic inflammation, we examined allergic rhinitis in IL-15 knockout (KO) mice sensitized with ovalbumin followed by intranasal rechallenge with ovalbumin. Methods: IL-15KO mice were sensitized intraperitoneally with ovalbumin/complete Freund's adjuvant on day 0 and ovalbumin/IFA on day 7, and then were intranasally challenged with ovalbumin on days 21, 22, 23, 24, and 25. Nasal symptoms and histologic changes were examined. IgE production and T H2 responses were measured by ELISA. Purified CD8 +T cells or recombinant IL-15 were administered into ovalbumin-sensitized mice. Results: The levels of IgE production and T H2 responses in IL-15KO mice were comparable to those in control mice after ovalbumin sensitization. However, sneezing, infiltration of eosinophils into the nasal mucosa, and T H2 cytokine production were aggravated in ovalbumin-sensitized IL-15KO mice after intranasal challenge with ovalbumin. Adoptive transfer of CD8 + T cells from ovalbumin-sensitized mice suppressed the T H2 responses in mice but not in IL-15KO mice. Administration of IL-15 with ovalbumin significantly prevented the development of allergic rhinitis in ovalbumin-sensitized mice. Conclusion: We demonstrate with IL-15KO mice that endogenous IL-15 plays an important role in suppression of allergic rhinitis at effector phase. Intranasal administration of IL-15 is useful as a therapeutic approach to control allergic rhinitis. Clinical implications: Intranasal administration of recombinant IL-15 might become new immunotherapy for allergic rhinitis.
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