MODULATION OF OXAZOLONE-INDUCED HYPERSENSITIVITY IN MICE BY SELECTIVEPDE INHIBITORS

THE effects of PDE inhibitors on oxazolone-induced contact hypersensit ivity (CS) were studied in mice. Rolipram, Ro 20-1724 and theophylline dose dependently inhibited CS but none caused >53% inhibition. ED(30) values at 24 h before challenge for rolipram, Ro 20-1724 and theophyl line were 2.1, 5.4 and 30.4 mg/kg, p.o., respectively. Milrinone and S KF 94836 at 30 mg/kg caused a small, but significant inhibition of 13% and 18%, respectively, although the inhibition (8%) caused by zaprina st was not significant. Betamethasone (10 mg/kg, p.o.) caused a marked inhibition (80%) as did indomethacin (65% at 5 mg/kg, p.o.). Rolipram and Ro 20-1724 inhibited proliferation of mouse lymphoblasts with IC5 0 values of 0.08 mu M and 0.83 mu M, respectively. In contrast, zaprin ast caused only a weak inhibition (IC50 = 119 mu M) of lymphocyte prol iferation, whereas SKF 94836 and theophylline failed to cause any sign ificant inhibition at 100 mu M (26% and 2%, respectively). These findi ngs suggest that PDE IV isozymes play a principal role in mediating CS by inhibiting lymphocyte activation.