[Skin reactions to bradykinin]

A large series of experiments carried out in animals and humans suggest that histamine release is not involved in the leakage phenomenon induced by bradykinin (BK) challenge. These experiments comprise in vitro studies on skin and bronchial human mast cells and in vivo studies on guinea pig airways and human skin using mepyramine, chlorpheniramine and terfenadine as reference H1-anti-histamines. Nevertheless, it has been shown recently that the H1 antagonist cetirizine 10 mg p.o. markedly inhibits skin reactions induced by BK challenge (intradermal injection of 212 micrograms BK in 10 microL saline and prick test with a solution of 21.2 micrograms/microL). In a guinea pig model, this drug also inhibited the bronchospasm induced by increasing concentrations of BK given by iv route (0.25 to 2 micrograms/Kg) and aerosol (3 to 300 micrograms/Kg). This inhibition was similar to the one obtained with the specific BK antagonist HOE 140 (15 pM/Kg). New data in the literature suggest the existence of various pharmacological mediators possibly involved in the BK-induced reaction: neuromediators, nitric oxyde and PAF. They also suggest that this reaction presents itself as a well defined sequence of pharmacological events. Since we could show that there is no binding of cetirizine to a human recombinant B2 receptor in vitro, some hypotheses are raised in order to explain this unexpected inhibiting effect of cetirizine.