EFFECTS OF A POTENT PLATELET-ACTIVATING-FACTOR ANTAGONIST, SR27417A, ON ALLERGEN-INDUCED ASTHMATIC RESPONSES

Platelet-activating factor (PAF) is a lipid-derived mediator that has been implicated in the pathophysiology of airway inflammation in asthm a. Its actions include chemotaxis and activation of inflammatory cells , particularly eosinophils. Inhaled PAF causes bronchoconstriction and increased airway responsiveness in human subjects. However, PAF antag onists have so far failed to show benefits in allergen challenge or in the treatment of chronic asthma. SR27417A is a novel PAF antagonist w ith increased potency compared with previously tested compounds. Twelv e asthmatic subjects received treatment with either SR27417A or placeb o for 1 wk in a double-blind crossover study. After treatment each sub ject underwent allergen challenge. Effects were assessed in terms of e arly and late asthmatic responses and allergen-induced effects on airw ay responsiveness. Baseline lung function and airway responsiveness we re also examined. Treatment with SR27417A significantly attenuated the late asthmatic response (AUC LAR(4-10h): 107 +/- 24 after placebo, 79 +/- 17 after SR27417A, p < 0.05; mean maximal percent fall in FEV1 LA R: 29 +/- 6% after placebo, 23.5 +/- 5.4% after SR27417A, p < 0.05). T here were no effects on early asthmatic responses, allergen-induced ai rway responsiveness, or baseline lung measurements. SR27417A is the mo st potent PAF antagonist to date, and it has a modest inhibitory effec t on the late asthmatic response. This suggests that PAF has a small r ole in allergic inflammation.