Prostaglandin E-2 decreases allergen-stimulated release of prostaglandin D-2 in airways of subjects with asthma

Prostaglandin E-2 (PGE(2)) inhibits the early and late bronchoconstrictor r esponse to inhaled allergen. The mechanisms of action, however, are not und erstood. We investigated the effect of inhaled PGE(2) on the release of pro staglandin D-2 (PGD(2)), preformed mast cell mediators, and other products of arachidonic acid metabolism. We compared inhaled PGE(2) (100 mu g) to pl acebo in a randomized double-blind crossover study. Ten atopic asthmatics u nderwent bronchoscopy immediately after inhalation of PGE, or placebo, Bron choalveolar lavage (BAL) was performed at baseline, and in a separate segme nt 4 min after allergen instillation. Nebulized PGE(2) was well tolerated. PGE(2) concentrations in baseline lavage fluid were significantly greater a fter PGE(2) inhalation than after placebo. PGD(2) concentrations after alle rgen challenge were significantly reduced in those subjects receiving nebul ized PGE(2) compared with control subjects. We conclude that PGE(2) can be safely delivered by inhalation, Nebulized PGE(2) administered before to seg mental allergen challenge reduced PGD(2) in BAL fluid (BALF), PGE(2) also d ecreased the production of other mediators of the arachidonic acid pathway, although not significantly. The reduction of PCD2 may be part of the mecha nism by which PGE(2) blocks the early asthmatic response.