W-56750

Murine allergic conjunctivitis was used to examine whether inhibition of CCR3 may have therapeutic effect.CCR3 antagonist of Benzyl-piperidin subclass, W-56750, was used to evaluate inhibitory effects of CCR3.Mice were sensitized with short ragweed, and orally administered for W-56750 for 3 consecutive days before and 1 day after allergen challenge to test anti-allergic effects.Early phase of allergen-specific immediate hypersensitivity reaction was evaluated by clin. symptoms, vascular permeability and mast cell degranulation.Late phase inflammatory responses were evaluated for inflammatory cell recruitment 24 h after allergen challenge.Clin. symptoms were significantly suppressed in W-56750-treated group (clin. score: vehicle-treated group 11.7 ± 0.8, W-56750 (30 mg/kg)-treated group 7.4 ± 0.6, P <0.01).Allergen-induced vascular permeability and mast cell degranulation were also significantly suppressed in W-56750-treated group.Allergen-induced late phase inflammatory responses, including recruitment of eosinophils, neutrophils, and mast cells, were significantly suppressed by W-56750 treatment (conjunctival eosinophil count: vehicle-treated group 29.6 ± 3.4, W-56750 (30 mg/kg)-treated group 6.6 ± 0.9, P <0.01).Treatment with W-56750 had potent anti-allergic effects for allergen-induced eosinophilia and inflammatory cell recruitment as well as mast cell-mediated clin. symptoms.Our data shows CCR3 inhibition may have promising therapeutic modality for allergic conjunctivitis.