IN-VITRO EFFECT OF CETIRIZINE ON PGE(2) RELEASE BY RAT PERITONEAL-MACROPHAGES AND HUMAN MONOCYTES

Cetirizine was first described as a specific anti-H-1 molecule displaying potent antiallergic activity. It was later found that its pharmacological properties extended to cellular actions as on eosinophil recruitment at inflammatory sites in allergic patients. Monocytes and macrophages participate in allergic mechanisms, particularly through high affinity H-1 and H-2 membrane receptors and generation of pro- and anti-inflammatory agents; among them histamine-induced factors, IL-1 and prostanoids are of importance. The aim of this work was to investigate the effect exerted by various concentrations of cetirizine (0.1-10 mu g/ml) applied in vitro to human monocytes and peritoneal rat macrophages cultured for 24 h. Peritoneal macrophages were collected either from normal or experimentally inflamed rats. Human monocytes, isolated from peripheral blood, were studied either in a resting state or after stimulation by LPS from Escherichia coli (1 and 10 mu g/ml). Cetirizine (10 mu g/ml) significantly enhanced IL-1 release by human monocytes stimulated by a weak LPS concentration (1 mu g/ml) but could not modify the maximal increase of IL-1 release induced by 10 mu g/ml of LPS. It did not exert any effect on resting cells. Cetirizine (0.1-10 mu g/ml) enhanced PGE(2) release by resting human monocytes. Concentrations of 1 and 10 mu g/ml enhanced PGE(2) release by LPS-stimulated monocytes, and by healthy and inflamed rat macrophages. This effect was concentration-dependent. Our findings point to an antiinflammatory action of cetirizine via PGE(2) release and histamine H-2 interactions. Cetirizine did not directly modify IL-1 generation by resting monocytes but the IL-1 production observed after LPS stimulation could promote the mechanisms by which PGE(2) is released.