Inhaled misoprostol blocks guinea pig antigen-induced bronchoconstriction and airway inflammation.
Inhaled E-type prostaglandins (PGE) have been shown to modulate responses to both allergic and nonallergic provocation. Misoprostol, a PGE1 analog, was developed as an antiulcer agent because it prevents gastrointestinal ulceration. Little is known about the effect inhaled misoprostol has on the airway and whether its potential antiasthmatic activity would be similar to other PGEs. Nebulizied solutions of misoprostol and PGE2 effectively blocked the acute bronchospasm caused by a subsequent inhaled antigen challenge in actively sensitized guinea pigs. The minimal concentration to result in a significant reduction in specific airway resistance was 3 and 30 micrograms/ml for misoprostol and PGE2, respectively. Exposure to a 300 micrograms/ml nebulized misoprostol solution provided significant protection for 2 h. Eosinophil recovery in bronchoalveolar lavage performed 24 h after antigen challenge was significantly reduced by 72%. In a chronic model of antigen-induced airway inflammation in which guinea pigs are given multiple antigen exposures over a 3-wk period, both misoprostol and its free acid-active metabolite 5C-30695 significantly reduced bronchoalveolar lavage eosinophils by 50 to 55%. Treatment with TRFK5, a monoclonal antibody to interleukin-5, resulted in a 76% decrease in eosinophil recovery. The combination of antibronchoconstrictive and anti-inflammatory effects suggests that inhaled misoprostol may be an effective treatment for the acute and chronic symptoms of asthma.
Smith
W G
WG
Department of Inflammatory Diseases Research, Searle Research and Development, Skokie, Illinois 60077, USA.
Thompson
J M
JM
Kowalski
D L
DL
McKearn
J P
JP
D000280:Administration, Inhalation; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000187:drug effects*; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D006168:Guinea Pigs; D015848:Interleukin-5 / Q000276:immunology; D008297:Male; D016595:Misoprostol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000517:prevention & control*
D000336:Aerosols; D018927:Anti-Asthmatic Agents; D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D016595:Misoprostol; C047042:misoprostol acid; D015232:Dinoprostone