Effects of single and multiple inhalations of platelet-activating factor on airway cell composition and responsiveness in monkeys

Authors


Dr Craig D. Wegner, Boehringer Ingelheim Pharmaceuticals, Inc., 90 East Ridge/P.O. Box 368, Ridgefield, CT 06877, U.S.A.

Summary

Platelet-activating factor (PAF) is a potent pro-inflammatory mediator that may play a role in the pathogenesis of airway hyper-responsiveness and asthma. In man, a single inhalation of PAF induces a small but prolonged increase in airway responsiveness in some individuals. The purpose of this study was to determine the effects of single and multiple inhalations of PAF on airway cell composition and responsiveness in monkeys. Anaesthetized and intubated adult male cynomolgus monkeys were studied. Airway cell composition was measured by bronchoalveolar lavage (BAL). Airway responsiveness was measured by determining the concentration (PC100) of inhaled methacholine that caused a 100% increase in respiratory system resistance (Rrs). Airway cell composition (BAL) and responsiveness (PC100) were determined 1 day before and 20 hr after a single inhalation of PAF (∼200 μg) or 3 days before (Day 0) and 3 days after (Day 10) 3-alternate-day (Days 3, 5 and 7) inhalations of PAF (each ∼600 μg). The single inhalation of PAF (n= 8) caused an acute increase in Rrs (147±69%), an increase in BAL granulocytes, and a decrease in PC100 in four of eight animals that was moderate (>eight fold) in only one animal. The mean ±s.e. change in log PC100 was −0.29±0.18. The multiple inhalations of PAF (n=8) caused acute increases in Rrs (143±38%, 175±44% and 156±39%, respectively), an increase in BAL granulocytes, and a decrease in PC100 in four of eight animals that was moderate in two animals. The mean±s.e. change in log PC100 was −0.43±0.22. In summary, single and multiple inhalations of PAF in monkeys induce a granulocyte airway infiltration and, in some animals, an increase (usually small) in airway responsiveness.

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