Effect of mometasone furoate on early and late phase inflammation in patients with seasonal allergic rhinitis.

BACKGROUND: Mometasone furoate is a potent glucocorticoid that can markedly inhibit proinflammatory Th2 cytokines in vitro. An aqueous nasal spray formulation has been shown to be clinically active in reducing the symptoms of perennial and seasonal allergic rhinitis. OBJECTIVE: To determine whether pretreatment with mometasone furoate 200 microg once daily decreases specific indices of early and late phase nasal inflammation compared with placebo. METHODS: A randomized, double-blind, placebo-controlled crossover study was conducted using nasal provocation with ragweed antigen in 21 patients with ragweed-induced allergic rhinitis out of the ragweed season; the treatment period was 2 weeks. Symptom scores, rhinoprobe cytology, and nasal lavage fluid were collected during early and late phase periods for nasal cytokines (interleukin, 1, 4, 5, 6, and 8) and leukotriene B4 determinations using ELISA and RIA. RESULTS: Mean nasal symptom scores and sneezing frequency were consistently lower with mometasone furoate compared with placebo. Treatment was associated with a statistically significant early phase (30-minute time point) reduction in nasal lavage histamine levels compared with placebo (14.3 versus 20.2 ng/mL, P = .02). Within-treatment comparisons suggested that mometasone furoate reduced the antigen-induced late-phase response for IL-6, IL-8, and eosinophils compared with pretreatment. There were similar, but smaller, changes seen in the placebo group for these measurements. There were no statistically significant changes following antigen challenge in IL-1, IL-4, IL-5, LTB4, or in other nasal cytology parameters. CONCLUSION: These results suggest that the clinical activity of mometasone furoate nasal spray in seasonal allergic rhinitis is likely due, in part, to a reduction in the levels of histamine in nasal secretions related to the early phase response, and reductions in IL-6, IL-8, and eosinophils during the late phase response.

Allergen-stimulated leukotriene B4 and interleukin-8 levels in patients with asthma and allergic rhinitis-modulation by a lipid pathway inhibitor.

BACKGROUND: Leukotriene B4 (LTB4), 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 LTB4 production and recruitment of eosinophils/neutrophils in bronchoalveolar fluid, could affect the production of LTB4 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 LTB4 and IL-8 levels using RIA and ELISA, respectively. RESULTS: Levels of LTB4 were significantly elevated in peripheral blood mononuclear cells stimulated with mold, grass, and tree compared with the unstimulated control group (P<.05). Levels of IL-8 were significantly elevated in all allergen-stimulated peripheral blood mononuclear cells, except mold, compared with the unstimulated control group (P<.05). Zileuton significantly reduced production of LTB4 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 LTB4 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.