Inhibition of mediator and cytokine release from dispersed nasal polyp cells by mizolastine.
BACKGROUND
Mizolastine is a potent and selective H1-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 microM) on the release of LT (LTB4 and LTC4/D4) and prostaglandin D2 (PGD2) 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 PGD2, the cells were preincubated with mizolastine or its dissolution vehicle for 20 min prior to challenge with 10 microg/ml epsilon-chain specific anti-IgE for 45 min at 37 degrees C; for the cytokine release, cells were incubated with mizolastine or its dissolution vehicle for 24 h. LT and PGD2 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/D4 at 10 microM, and GM-CSF from 1 microM; no effect was observed on the release of PGD2.


CONCLUSIONS
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.
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D009298:Nasal Polyps / Q000188:drug therapy* / Q000378:metabolism*; D009360:Neoplastic Cells, Circulating / Q000187:drug effects* / Q000378:metabolism; D016896:Treatment Outcome
D000888:Antibodies, Anti-Idiotypic; D001562:Benzimidazoles; D016207:Cytokines; D006634:Histamine H1 Antagonists; D018836:Inflammation Mediators; C026408:anti-IgE antibodies; C076170:mizolastine