Pharmaceutical and Histopathological Analyses of the Developing Mechanism of Severe Allergic Conjunctival Diseases Using Experimental Animal Models: Roles of Systemic and Local Cytokines

Atsuki      Fukushima

Abstract

Eosinophils are major effector cells for the development of severe allergic conjunctival diseases (ACD), such as vernal keratoconjunctivitis. Recruitment of eosinophils into the conjunctiva is mediated by chemokines and cytokines. In this review, using an animal model for ACD (experimental immune-mediated blepharoconjunctivitis, EC), the roles of cytokines for eosinophil infiltration into the conjunctiva are presented. Using cytokine knockout mice, importance of endogenous IL-4 for eosinophil infiltration was confirmed. In contrast, endogenous IFN-γ was identified to be inhibitory for eosinophil infiltration. When EC was induced by transfer of in vitro-stimulated antigen (Ag)-primed lymphocytes, then the addition of IL-4 to the culture augmented eosinophil infiltration. Systemic administration of IFN-γ suppressed EC only when IFN-γ was injected during the induction phase. Concerning cytokines in the conjunctiva, expression of Th1 cytokines increased timedependently, whereas that of Th2 cytokines peaked at 12 hours after Ag challenge. In accord with the data, macrophage infiltration increased in a time-dependent manner, while eosinophil infiltration peaked at 12 hours. Subconjunctival injection of IL-4, as well as eotaxin, induced eosinophil infiltration into the conjunctiva. This IL- 4-induced eosinophil infiltration was inhibited by co-injection of IFN-γ. Taken altogether, both systemic and local IL-4 is important for eosinophil infiltration into the conjunctiva and is regulated by IFN-γ.

Keywords: allergic conjunctival diseases, papillae, fibroblasts, autoimmune diseases, short ragweed pollen

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