EFFECT OF IN-VIVO AND IN-VITRO LOVASTATIN TREATMENT ON MAST-CELL ACTIVATION

The hydroxymethylglutaryl coenzmye A (HMG CoA) reductase inhibitor lov astatin is used to treat hyperlipidaemia. This agent prevents the isop renylation of some proteins involved in signal transduction processes and inhibits IgE-receptor-linked mediator release from RBL-2H3 cells. In this study the effect of in vivo and in vitro administration of lov astatin on histamine release from rat peritoneal mast cells was examin ed. Lovastatin (4 mg/kg/day for 2 weeks) inhibited histamine release i nduced by concanavalin A (con A) from rat peritoneal mast cells of Hoo ded-Lister rats and both homozygous lean and obese Zucker rats. In con trast, release induced by antirat IgE (anti-IgE) was only significantl y inhibited in cells derived from Hooded-Lister rats and that induced by compound 48/ 80 was not altered. Lovastatin (20 mu M, 24 h, in vitr o) caused a significant inhibition of the subsequent histamine release to con A, anti-IgE and compound 48/80 but not to the calcium ionophor e A 23187. It is important to determine whether such inhibitory effect s are also observed after the chronic, clinical administration of lova statin and other HMG CoA reductase inhibitors.