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首页> 外文期刊>Clinical and experimental allergy : >Effect of tecastemizole on pulmonary and cutaneous allergic inflammatory responses.
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Effect of tecastemizole on pulmonary and cutaneous allergic inflammatory responses.

机译：替卡米唑对肺和皮肤过敏性炎症反应的影响。

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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.
机译：背景：替卡米唑是阿司咪唑的主要代谢产物，是一种有效的选择性H1受体拮抗剂。有证据表明，这种和某些其他H1受体拮抗剂可能具有抗炎作用，在某些情况下，它们与H1受体拮抗作用无关。目的本研究的目的是研究替卡司咪唑在过敏性炎症模型中的抗炎作用。方法：在过敏性肺部炎症的鼠模型，豚鼠皮肤的被动皮肤过敏反应（PCA）和体外测定内皮粘附分子表达和白细胞与内皮粘附的体外试验中，评估替卡替米唑的作用。结果：替卡米唑以剂量依赖性方式抑制了抗原诱导的嗜酸性粒细胞向过敏性小鼠肺部的募集。此外，在该模型中，亚有效剂量的替卡米唑与亚有效剂量的地塞米松的组合抑制了嗜酸性粒细胞的积累。 tecastemizole抑制了PCA反应中的血浆外渗，尽管其机制似乎是H1受体依赖性的。 tecastemazole以独立于H1受体拮抗的方式抑制细胞因子诱导的内皮细胞间粘附分子1和血管细胞粘附分子1的表达，以及单核细胞对人脐静脉内皮细胞的粘附。结论：这些数据表明替卡米唑在抑制晚期炎症反应中可能具有H1受体非依赖性作用，而急性反应似乎以H1受体依赖性方式被抑制。此外，我们的数据表明此类药物在过敏性炎症疾病的治疗中具有重要的潜在的类固醇保护作用。

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