CAMP-SPECIFIC PHOSPHODIESTERASE INHIBITOR, ROLIPRAM, REDUCES EOSINOPHIL INFILTRATION EVOKED BY LEUKOTRIENES OR BY HISTAMINE IN GUINEA-PIG CONJUNCTIVA

The effect of rolipram, an isozyme IV-selective inhibitor of cAMP-specific phosphodiesterase, was evaluated in a guinea pig eye model of tissue eosinophilia (R)-rolipram was administered by gavage to guinea pigs 1 h prior to topical ocular challenge with a mixture of leukotrienes (LTs) (10 ng LTB4 + 1000 ng LTD4/eye) or with histamine dihydrochloride (1 mg/eye). Conjunctivae were evaluated histologically 6 h after challenge. Eosinophil counts per millimeter of conjunctival epithelium in LT-challenged animals that received (R)-rolipram at dosages of 0.1, 0.3, 1, 3, or 10 mg/kg were reduced by 63, 63, 84, 81 and 90% respectively, compared to LT-challenged controls. Reduction was statistically significant (P < 0.05) at all dosages. Eosinophil counts per millimeter of epithelium in histamine challenged animals that received 10 mg/kg (R)-rolipram were reduced by 79% compared to histamine-challenged controls (P < 0.01). The results indicate that (R)-rolipram inhibits the response to two distinct classes of mediator in this model of eosinophil infiltration, adding support to the contention that isozyme IV-selective cAMP phosphodiesterase inhibitors offer therapeutic potential for human asthma.