The effect of cetirizine on antigen-dependent leucopenia in the guinea-pig.
1. Intravenous administration of ovalbumin (1 mg kg-1) to guinea-pigs that had previously been injected with 3.5 x 10(9) 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. 2. In contrast, there was no change in the leucocyte number following antigen challenge of guinea-pigs that had received platelets from non-immunised animals. 3. 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 micrograms kg-1 of histamine. 4. 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. 5. 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. 6. 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.
Unité de Pharmacologie Cellulaire, INSERM No. 285, Paris, France.
A J
AJ
Coyle
J
J
Lefort
B B
BB
Vargaftig
D000818:Animals; D044482:Benzeneacetamides; D001559:Benzhydryl Compounds / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D017332:Cetirizine; D005260:Female; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology; D006919:Hydroxyzine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007958:Leukocyte Count; D007970:Leukopenia / Q000276:immunology / Q000517:prevention & control*; D007975:Leukotriene B4 / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D016593:Terfenadine
D044482:Benzeneacetamides; D001559:Benzhydryl Compounds; D006634:Histamine H1 Antagonists; D006877:Hydroxamic Acids; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; C056614:N-(3-phenoxycinnamyl)acetohydroxamic acid; D007975:Leukotriene B4; D006919:Hydroxyzine; D016593:Terfenadine; D011738:Pyrilamine; D017332:Cetirizine