Pharmacological modulation of PAF-acether-induced pleurisy in rats

Abstract Injection of platelet-activating factor (PAF-acether) into the pleural cavity of rats induced the accumulation of a moderately intense exudate within 30 to 60 minutes. By comparison with animals given injections of the vehicle alone, the animals given this mediator had elevated levels of leukotriene C 4 -immunoreactive material (LTC 4 im) in the exudate and decreased quantities of thromboxane B 2 (TxB 2 ) and of 6-KetoF 1α -prostaglandin (6-Keto PGF 1α ). Nifedipine, verapamil, and diltiazem reduced the pleural exudate with no major effect on the mediators. Both salbutamol and theophylline reduced the exudate and the levels of LTC 4 im. Acetylsalicylic acid, phenylbutazone and indomethacin significantly inhibited the exudate, greatly lowered the quantities of cyclooxygenase derivatives and tended to increase LTC 4 im. Phenidone, which inhibits the cyclooxygenase and lipoxygenase pathways, decreased the exudate and the three mediators. The phospholipase A 2 inhibitor, chloroquine, decreased both the amount of exudate and moderately the concentration of LTC 4 im. The glucocorticoids studied had no effect on the exudate or on the mediators. These results suggest that the role of the increased LTC 4 im in the induction of the pleurisy is not clear