Abstract
Purpose::
To examine therapeutic efficacy of CCR3 blockade for experimental allergic conjunctivitis.
Methods::
Murine allergic conjunctivitis was used to examine whether inhibition of CCR3 may have therapeutic effect. Short-ragweed-sensitized mice were challenged by allergen instillation to provoke allergic conjunctivitis. CCR3 antagonist of Benzyl-piperidin subclass, W-56750, was orally administered for 3 consecutive days before allergen challenge to test therapeutic effects on early phase and late phase parameters (clinical symptoms, vascular permeability evaluated by dye dilution method, and histological evaluation of inflammatory cell recruitment).
Results::
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 < 0.05). Clinical symptoms were significantly suppressed in W-56750-treated group (clinical score: vehicle-treated group 11.7 ± 0.8, W-56750 (30 mg/kg)-treated group 7.4 ± 0.6, P < 0.05). Vascular permeability and allergen-induced mast cell degranulation were also significantly suppressed in W-56750-treated group.
Conclusions::
Treatment with W-56750 had potent anti-allergic effects for allergen-induced eosinophilia and inflammatory cell recruitment as well as mast cell-mediated clinical symptoms. Our data shows CCR3 inhibition may have promising therapeutic modality for allergic conjunctivitis.
Keywords: conjunctivitis • inflammation • drug toxicity/drug effects