Treatment with FTY720 during the induction or effector phase suppresses the development of experimental allergic conjunctivitis in mice

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Tel.: +81 88 880 2391; fax: +81 88 880 2392. E-mail addresses: fukusima@kochi-u.ac.jp

Abstract

Purpose: To investigate whether experimental allergic conjunctivitis (EC) can be suppressed by treatment with the immunomodulatory drug FTY720, which reduces the recruitment of effector T cells into inflammatory sites.

Methods: BALB/c mice were actively immunized with ragweed (RW) and then injected intraperitoneally with FTY720 on days 0, 2, 4, 6 and 8 (induction phase treatment) followed by challenge on day 10 with RW-containing eye drops. Alternatively, naïve mice that received RW-primed splenocytes were injected intraperitoneally with FTY720 on days 2 and 4 (effector phase treatment) followed by RW challenge on day 4. Twenty-four hours after RW challenge, conjunctivas and spleens were harvested for histology or immunohistochemistry, and flow cytometric analysis or cytokine assays, respectively.

Results: FTY720 treatment during the induction phase suppressed the conjunctival infiltration of T cells as well as eosinophils and macrophages. The splenocytes from induction phase-treated mice contained significantly less CD4+ and CD8+ T cells and showed significant suppression of Th2 but not Th1 cytokine production. Effector phase treatment with FTY720 suppressed conjunctival eosinophil infiltration.

Conclusions: These data demonstrate that FTY720 treatment during the induction phase decreases the absolute number of CD4+ and CD8+ T cells in the spleen and suppresses Th2 cytokine production by splenocytes. This leads to the suppression of EC. FTY720 treatment also suppresses EC when delivered during the effector phase. Thus, FTY720 treatment may be suitable for treating severe forms of vernal keratoconjunctivitis.

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