Allergen-Stimulated Leukotriene B4 and Interleukin-8 Levels in Patients with Asthma and Allergic Rhinitis-Modulation by a Lipid Pathway Inhibitor

Background Leukotriene B 4 (LTB 4 ), a potent chemokinetic mediator for neutrophils, is enhanced by interleukin-8 (IL-8) and may play a key role in the inflammatory response of asthma. Objective The aim of the present study was to investigate whether zileuton, a 5-lipoxygenase antagonist known to inhibit LTB 4 production and recruitment of eosinophils/neutrophils in bronchoalveolar fluid, could affect the production of LTB 4 and IL-8 by allergen-stimulated peripheral blood mononuclear cells in vitro from patients with asthma and/or allergic rhinitis. Methods Peripheral blood mononuclear cells were isolated using Ficoll-Hypaque density gradient from 14 subjects (2 with asthma, 11 with asthma and allergic rhinitis, and 1 with allergic rhinitis) and were stimulated by selected allergens (grass, tree, mite, and mold) in the absence or presence of 1 and 10 microM of zileuton. Supernatants were collected and assayed for LTB 4 and IL-8 levels using RIA and ELISA, respectively. Results Levels of LTB 4 were significantly elevated in peripheral blood mononuclear cells stimulated with mold, grass, and tree compared with the unstimulated control group ( P P 4 by mold and tree-stimulated peripheral blood mononuclear cells. By contrast, no effect of zileuton on IL-8 production was observed in allergen-stimulated peripheral blood mononuclear cells. Conclusions The zileuton-induced attenuation of LTB 4 production by allergen-stimulated peripheral blood mononuclear cells from patients with asthma and/or allergic rhinitis occurs independently from the allergen-stimulated IL-8 production.