Pharmacological modulation of PAF-acether-induced pleurisy in rats.

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 C4-immunoreactive material (LTC4 im) in the exudate and decreased quantities of thromboxane B2 (TxB2) and of 6-Keto-F1 alpha-prostaglandin (6-Keto PGF1 alpha). 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 LTC4 im. Acetylsalicylic acid, phenylbutazone and indomethacin significantly inhibited the exudate, greatly lowered the quantities of cyclooxygenase derivatives and tended to increase LTC4 im. Phenidone, which inhibits the cyclooxygenase and lipoxygenase pathways, decreased the exudate and the three mediators. The phospholipase A2 inhibitor, chloroquine, decreased both the amount of exudate and moderately the concentration of LTC4 im. The glucocorticoids studied had no effect on the exudate or on the mediators. These results suggest that the role of the increased LTC4 im in the induction of the pleurisy is not clear.