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

• Published in: Allergy (Copenhagen) Vol. 57; no. 11; pp. 1067 - 1070
• Main Authors: Carayol, N., Crampette, L., Mainprice, B., Ben‐Soussen, Paul, Verrecchia, M., Bousquet, J., Lebel, B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Munksgaard International Publishers 01-11-2002; Blackwell
• Subjects: Adult; Antibodies, Anti-Idiotypic - administration & dosage; Antibodies, Anti-Idiotypic - therapeutic use; Benzimidazoles - therapeutic use; Biological and medical sciences; Cell Survival - drug effects; cytokines; Cytokines - drug effects; Cytokines - metabolism; Dose-Response Relationship, Drug; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Female; Histamine and antagonists. Allergy; Histamine H1 Antagonists - administration & dosage; Histamine H1 Antagonists - therapeutic use; Humans; Inflammation Mediators - metabolism; Leukocytes - cytology; Leukocytes - drug effects; Leukocytes - metabolism; leukotrienes; Male; Mast Cells - cytology; Mast Cells - drug effects; Mast Cells - metabolism; Medical sciences; Middle Aged; mizolastine; nasal polyps; Nasal Polyps - drug therapy; Nasal Polyps - metabolism; Neoplastic Cells, Circulating - drug effects; Neoplastic Cells, Circulating - metabolism; Pharmacology. Drug treatments; Treatment Outcome; Human; Immunopathology; Allergy; Nose disease; Mizolastine; Prostaglandin; Rhinitis; Arachidonic acid derivatives; Cytokine; Leukotriene; Chemotherapy; Treatment; Polypeptide; Benzimidazole derivatives; ENT disease; Antagonist; Mechanism of action; H1 Histamine receptor; Tumor necrosis factor α; Granulocyte macrophage colony stimulating factor; Polyp
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1034/j.1398-9995.2002.23452.x

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‐α (TNF‐α). This study investigated the effects of three concentrations of mizolastine (0.1, 1.0, 10 µM) 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‐α 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 µg/ml ε‐chain specific anti‐IgE for 45 min at 37°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‐α at all concentrations, LTC4/D4 at 10 µM, and GM‐CSF from 1 µM; no effect was observed on the release of PGD2.
Conclusion Mizolastine inhibits the release of LT, TNF‐α and GM‐CSF in this in vitro model, which mimics closely the inflammatory cells of allergic rhinitis.