Inhibition of mediator and cytokine release from dispersed nasal polyp cells by mizolastine

Background: Mizolastine is a potent and selective H-1-receptor antagonist with antiallergic properties; in in-vitro animal models, mizolastine was shown to inhibit 5-lipoxygenase activity and to decrease the release of leukotrienes (LT) and tumor necrosis factor-alpha (TNF-alpha). This study investigated the effects of three concentrations of mizolastine (0.1, 1.0, 10 muM) on the release of LT (LTB (4) and LTC4/D-4) and prostaglandin D-2 (PGD(2)) after stimulation by anti-IgE, and on the spontaneous release of cytokines (TNF-alpha and granulocyte/macrophage-colony-stimulating factor [GM-CSF]), from dispersed cells obtained from surgically resected nasal polyps of patients with nasal polyposis. Methods: Cells from nasal polyps were obtained using enzymatic dispersion. For experiments involving the measurement of LT and PGD(2), the cells were preincubated with mizolastine or its dissolution vehicle for 20 min prior to challenge with 10 mug/ml epsilon-chain specific anti-IgE for 45 min at 37degreesC; for the cytokine release, cells were incubated with mizolastine or its dissolution vehicle for 24 h. LT and PGD(2) were measured by enzyme immunoassay (EIA) and cytokines by enzyme-linked immunosorbent assay (ELISA) using commercially available kits. Results: Mizolastine inhibited significantly and in a dose-dependent manner the release of LTB4 and TNF-alpha at all concentrations, LTC4/D-4 at 10 muM, and GM-CSF from 1 muM; no effect was observed on the release of PGD(2). Conclusion: Mizolastine inhibits the release of LT, TNF-alpha and GM-CSF in this in vitro model, which mimics closely the inflammatory cells of allergic rhinitis.