Abstract
Background: The effects of the non-impairing, H 1-receptor antagonist fexofenadine were investigated in in vivo mouse models of eosinophilia and systemic anaphylaxis. Methods: Eosinophilia was investigated in C57BL/6 mice ( n=5 per group) infected with Trichinella spiralis, with and without administration of fexofenadine HCl (5, 10 and 20 mg/kg/day). Eosinophilia was also studied, with and without fexofenadine administration, in mice with a congenital mast-cell deficiency (W/W v) and controls (+/+). The effect of fexofenadine HCl (20 mg/kg/day) on IL-5 and eotaxin blood levels was also investigated in C57BL/6 mice. In a separate model, systemic anaphylaxis was induced in C57BL/6 mice using T. spiralis antigen. Fexofenadine HCl (5, 10 and 20 mg/kg) or vehicle was administered 20 min before antigen challenge ( n=5 per group). The effect of fexofenadine on systemic anaphylaxis caused by IgE and anti-IgE was also examined in CBF1 mice injected with serum from NC/Nga mice with high IgE levels. Rectal temperature was measured as an indicator of anaphylaxis. Results: In C57BL/6 mice, repetitive oral administration of fexofenadine HCl (5, 10 and 20 mg/kg/day) resulted in dose-dependent suppression of eosinophilia ( p<0.05–0.0001). No suppression was observed in mast-cell deficient W/W v mice. In addition, single oral administration of fexofenadine HCl (10 and 20 mg/kg) significantly suppressed the decrease in rectal temperature ( p<0.01), a marker for systemic anaphylaxis, in C57BL/6 mice. In CBF1 mice injected with serum from NC/Nga mice with high IgE levels, the decrease in rectal temperature was suppressed by single administration of fexofenadine HCl (10 and 20 mg/kg; p<0.01 and p<0.001, respectively). Fexofenadine had no effect on peripheral IL-5 and eotaxin levels. Conclusion: These results indicate that fexofenadine suppresses both eosinophilia and systemic anaphylaxis, both of which are fundamental reactions in allergic diseases.
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