Effect of tecastemizole on pulmonary and cutaneous allergic inflammatory responses

Lever, R., Hefni, A., Moffatt, J.D., Paul, W. and Page, C.P. (2007) Effect of tecastemizole on pulmonary and cutaneous allergic inflammatory responses. Clinical & Experimental Allergy, 37 (6). p. 909. 10.1111/j.1365-2222.2007.02730.x.

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DOI: 10.1111/j.1365-2222.2007.02730.x

Abstract

Background Tecastemizole, a major metabolite of astemizole, is a potent and selective H1 receptor antagonist. Evidence suggests that this and certain other H1 receptor antagonists may possess anti-inflammatory effects that are, in some cases, independent of H1 receptor antagonism. Objective The aim of this study was to investigate the anti-inflammatory effects of tectastemizole in models of allergic inflammation. Methods Effects of tecastemizole were assessed in a murine model of allergic lung inflammation, in passive cutaneous anaphylaxis (PCA) responses in guinea-pig skin and in in vitro assays measuring endothelial adhesion molecule expression and leucocyte–endothelial adhesion. Results Tecastemizole inhibited antigen-induced eosinophil recruitment to the lungs of allergic mice in a dose-dependent manner. Furthermore, combination of a sub-effective dose of tecastemizole, combined with a sub-effective dose of dexamethasone inhibited eosinophil accumulation in this model. Plasma extravasation in PCA reactions was inhibited by tecastemizole, although by a mechanism that would appear to be H1 receptor-dependent. Cytokine-induced endothelial intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, as well as mononuclear cell adhesion to human umbilical vein endothelial cells was inhibited by tecastemazole in a manner independent of H1 receptor antagonism. Conclusion These data suggest that tecastemizole may have H1 receptor-independent effects in inhibiting late-phase inflammatory responses, while acute responses appear to be inhibited in a H1 receptor-dependent manner. Furthermore, our data suggest an important potential steroid-sparing role for such drugs in the treatment of allergic inflammatory conditions.

Item Type:Article
Uncontrolled Keywords:adhesion;allergy;antihistamine;asthma;endothelium;eosinophil;glucocorticosteroid;H1 receptor;histamine;PCA
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:3184
Journal or Publication Title:Clinical & Experimental Allergy
Deposited By:Library Staff
Deposited On:10 May 2012 12:27
Last Modified:10 May 2012 12:27

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