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Effect of terfenadine on human eosinophil and neutrophil chemotactic response and generation of superoxide.

Second generation antihistamines have been reported to have anti-inflammatory properties in addition to their potency as H1 antagonists. In this in-vitro study, we evaluated the effect of terfenadine on platelet activating factor-(PAF)-induced or N-formyl-methionyl-leucyl-phenylamine-(FMLP)-induced human eosinophil and neutrophil chemotactic responses; and on superoxide anion generation from human eosinophils and neutrophils activated by either PAF, calcium ionophore (A23187) or phorbol myristate acetate. Since eosinophil degranulation is also associated with tissue inflammation, we further examined the effect of terfenadine on the PAF-induced release of eosinophil cationic protein. The peak concentration of terfenadine-related materials in serum of adult individuals after 60 mg of oral administration has been reported to be 351 +/- 0.4 ng/mL. We therefore used 100 to 1000 ng/mL concentrations of terfenadine. Purified normodense-eosinophils and neutrophils were obtained by discontinuous gradient from allergic subjects. We observed that terfenadine had greater inhibitory effects on eosinophils than neutrophils in both chemotactic response and superoxide generation. Terfenadine, at concentrations of 500 and 1000 ng/mL, significantly inhibited PAF-induced and FMLP-induced eosinophil chemotaxis, whereas 1000 ng/mL of terfenadine was necessary to suppress neutrophil chemotaxis. Terfenadine, at concentrations achievable at standard dosing regimens, has anti-inflammatory properties in vitro.