Am. J. Respir. Crit. Care Med., Volume 162, Number 2, August 2000, 637-640

Prostaglandin E₂ Decreases Allergen-stimulated Release of Prostaglandin D₂ in Airways of Subjects with Asthma

TINA V. HARTERT, RYSZARD T. DWORSKI, BEVERLY G. MELLEN, JOHN A. OATES, JOHN J. MURRAY, and JAMES R. SHELLER

Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, and Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee; and the Section on Biostatistics, Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Prostaglandin E₂ (PGE₂) inhibits the early and late bronchoconstrictor response to inhaled allergen. The mechanisms of action, however, are not understood. We investigated the effect of inhaled PGE₂ on the release of prostaglandin D₂ (PGD₂), preformed mast cell mediators, and other products of arachidonic acid metabolism. We compared inhaled PGE₂ (100 µg) to placebo in a randomized double-blind crossover study. Ten atopic asthmatics underwent bronchoscopy immediately after inhalation of PGE₂ or placebo. Bronchoalveolar lavage (BAL) was performed at baseline, and in a separate segment 4 min after allergen instillation. Nebulized PGE₂ was well tolerated. PGE₂ concentrations in baseline lavage fluid were significantly greater after PGE₂ inhalation than after placebo. PGD₂ concentrations after allergen challenge were significantly reduced in those subjects receiving nebulized PGE₂ compared with control subjects. We conclude that PGE₂ can be safely delivered by inhalation. Nebulized PGE₂ administered before to segmental allergen challenge reduced PGD₂ in BAL fluid (BALF). PGE₂ also decreased the production of other mediators of the arachidonic acid pathway, although not significantly. The reduction of PGD₂ may be part of the mechanism by which PGE₂ blocks the early asthmatic response.

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