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Molecular Pharmacology of Antihistamines in Inhibition of Oxidative Burst of Professional Phagocytes

Nosáľ R, Drábiková K, Jančinová V and Perečko T

Antihistamines of the H1 and H3/H4 groups interfere with oxidative burst of human professional phagocytes. Of H1 antihistamines, the most effective was dithiaden suppressing oxidative burst of whole human blood and chemiluminescence of isolated neutrophils both at extra- and intracellular level. Generation of free oxygen radicals in isolated neutrophils resulted most probably from the inhibition of proteinkinase C activation, as demonstrated for dithiaden. The differences in H1 antihistamines to inhibit oxidative burst of professional phagocytes correlates with their physicochemical properties, particularly with partition coefficient. The potentiation of recombinant caspase-3 by dithiaden is supportive of the antiinflammatory effect of dithiaden similarly to H1 antihistamines, by increasing the apoptosis of professional phagocytes. Of the H3/H4 antihistamines, the most effective was JNJ 7777 120 followed by JNJ 1019 1584. Thioperamide was less effective and it slightly potetntiated generation of free oxygen radicals. Their results demonstrated H1 antihistamines to be much more potent in the inhibition of free oxygen generation in human professional phagocytes as compared with the H3/H4 antihistamines investigated. This finding should be taken into account therapeutically.