Effects of mizolastine in vitro on human immunocompetent and airway cells: evidence for safety and additional property.
BACKGROUND
Mizolastine is a potent, peripherally acting, selective H1-receptor antagonist with potential anti-inflammatory properties. The aim of the study was to evaluate the in vitro effects of mizolastine on the expression of adhesion molecules by primary human airway epithelial and stromal cultures; moreover, the activity of mizolastine on parameters which reflect the immune response efficacy was investigated.


METHODS
Airway epithelial and stromal cells were collected from hypereosinophilic subjects by enzymatic digestion of polyps or turbinates. Cells were stimulated with interferon (IFN)-gamma (500 IU/ml) in the presence of various mizolastine concentrations (6 x 10(-8)-6 x 10(-6) M) for 24 h and the expression of CD106, CD54, CD58 and HLA class I was evaluated. Peripheral blood mononuclear cells from healthy volunteers were incubated with 1% phytohemagglutinin or anti-CD3 monoclonal antibody (20 ng/ml) in the presence of mizolastine, then T lymphocyte proliferation, HLA-DR expression and T cell subpopulations were evaluated.


RESULTS
Both in epithelial and stromal cultures, IFN-gamma significantly upregulated all of the tested surface molecules (p<0.05). The highest dose of mizolastine (6 x 10(-6) M), corresponding to 10-fold the peak plasma level after a single oral administration of 10 mg, was able to act on fibroblasts, significantly downregulating the expression of CD54 (p<0.05). Regarding T lymphocyte proliferation, the addition of mizolastine did not induce any significant change; furthermore, mizolastine was ineffective at all of the tested concentrations on both HLA-DR expression and CD4+/CD8+ ratio.


CONCLUSIONS
This study demonstrated that mizolastine is able to selectively downregulate CD54 expression on stimulated stromal but not epithelial cells without impairing the immune system effectors. The possible clinical significance of these results are an antiallergic property and CD54 modulation on fibroblasts with a good safety profile as far as the lymphocyte response is concerned.
Oddera
S
S
Allergy and Respiratory Diseases Service, DIMI, Genoa, Italy.
Cagnoni
F
F
Dellacasa
P
P
Canonica
G W
GW
D000293:Adolescent; D000328:Adult; D000368:Aged; D001562:Benzimidazoles / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007371:Interferon-gamma / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects* / Q000276:immunology; D009298:Nasal Polyps / Q000188:drug therapy / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects
D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; D018799:Intercellular Adhesion Molecule-1; C076170:mizolastine; D007371:Interferon-gamma