Am. J. Respir. Crit. Care Med., Vol 154, No. 2, 08 1996, 295-299.
Inhaled misoprostol blocks guinea pig antigen-induced bronchoconstriction and airway inflammation
WG Smith, JM Thompson, DL Kowalski and JP McKearn
Department of Inflammatory Diseases Research, Searle Research and Development, Skokie, Illinois 60077, USA.
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.
