The effect of cetirizine on antigen‐dependent leucopenia in the guinea‐pig

Abstract

Intravenous administration of ovalbumin (1 mg kg−1) to guinea‐pigs that had previously been injected with 3.5 × 109 platelets from actively sensitized animals induced an approximately 40% decrease in the number of circulating leucocytes 30–60 min later, whereas the number of platelets was not affected. In contrast, there was no change in the leucocyte number following antigen challenge of guinea‐pigs that had received platelets from non‐immunised animals. This platelet‐dependent leucopenia was inhibited by prior treatment of the recipient animal with cetirizine (10–30 mg kg−1, i.v.). Terfenadine (50 mg kg−1, p.o.) and mepyramine (2 mg kg−1, i.v.) were completely inactive in this respect. All doses of anti‐histamines were used at concentrations which completely inhibited the bronchoconstriction to an i.v. injection of 5 μg kg−1 of histamine. The site of action of cetirizine is most likely to be the platelet as leucopenia induced by the neutrophil agonists leukotriene B4 (LTB4) (30 ng kg−1) and platelet activating factor (PAF) (30 ng kg−1) were not modified by cetirizine treatment. In these experiments, we failed to support a role for lipoxygenase products as mediators of the platelet‐dependent leucopenia, as the selective lipoxygenase inhibitor BWA4C (50 mg kg−1, p.o.) was ineffective. Our present results confirm and extend previous data demonstrating that antigen stimulated platelets can induce leucopenia in non‐immunised animals and this can be inhibited by the anti‐allergic agent, cetirizine, by an action which is probably unrelated to its anti‐histamine properties. The precise nature of the platelet derived factor(s) and their target of action remains to be determined.