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Interference of cetirizine with the late eosinophil accumulation induced by either PAF or compound 48/80
Author(s) -
Martins Marco A.,
Pasquale Claudia P.,
Silva Patrícia M.R.,
Pires Ana L.A.,
Ruffié Claude,
Rihoux Jean P.,
Cordeiro Renato S.B.,
Vargaftig B. Boris
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14231.x
Subject(s) - cetirizine , eosinophil , eosinophilia , ed50 , histamine , antagonist , pharmacology , receptor antagonist , leukotriene d4 , histamine h1 receptor , receptor , medicine , chemistry , endocrinology , immunology , asthma
1 The effect of topical or systemic treatment with the histamine H 1 ‐receptor antagonist, cetirizine, on the rat pleural eosinophil accumulation induced by PAF or compound 48/80 was investigated. The number of pleural resident eosinophils increased 6 h after the intrathoracic (i.t.) injection of PAF (1 μg/cavity), peaked within 24 h and persisted significantly augmented for at least 96 h. Compound 48/80 (25 μg/cavity) also produced a long lasting pleural eosinophilia but this was first noted only 24 h after stimulation. 2 Intraperitoneal pretreatment with cetirizine inhibited eosinophilia induced by either PAF (ED 50 = 19 mg kg −1 ) or compound 48/80 (ED 50 = 14 mg kg −1 ) whereas meclizine, another histamine H 1 ‐receptor antagonist, was inactive. 3 Administered locally, cetirizine (5 and 15 μg/cavity) also dose‐dependently inhibited both PAF‐ and compound 48/80‐induced eosinophilia, providing evidence that its inhibitory effect is not due to any action upon circulating eosinophils. Consistent with this result, incubation of isolated peritoneal eosinophils with cetirizine failed to modify in vitro eosinophil migration caused by PAF. 4 Since the late eosinophilia induced by PAF may depend on the synthesis of a transferable protein mediator, cetirizine was administered to donor or recipient rats in order to determine whether it interferes with the generation or with the expression of this protein. We showed that only the treatment of recipient rats abolished the transfer of the eosinophilotactic activity, indicating that cetirizine does not modify the generation but inhibits the expression of this activity. 5 Our findings indicate that cetirizine is able to inhibit eosinophil accumulation by acting locally. The mechanism is neither related to its recognized ability to antagonize histamine H 1 ‐receptors nor to a direct action upon circulating eosinophils.