Pimecrolius on T cell Responses in Atopic March

皮美克留斯 (Pimecrolius) 论特应性三月中的 T 细胞反应

• 批准号: 7169879
• 负责人: JONATHAN Micheal SPERGEL
• 金额: $ 34.9万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7169879
• 关键词: Agonist; Albuterol; Allergens; Asthma; Atopic Dermatitis; Betula Genus; Biological Assay; Breathing; Cells; Child; Clinical Trials; Controlled Study; Cream; Cutaneous; Development; Diagnosis; Disease; Double-Blind Method; Early treatment; Exhalation; Felis catus; Flow Cytometry; Frequencies; Goals; HLA Antigens; Homing; IgE; Infant; Measures; Nitric Oxide; Novartis brand of pimecrolimus; Patients; Peripheral Blood Mononuclear Cell; Pharmacologic Substance; Phenotype; Pimecrolimus; Pollen; Prevalence; Prevention; Process; Production; Pyroglyphidae; Randomized; Role; Safety; Serum; Skin; Spirometry; Staphylococcus aureus; Superantigens; T-Cell Activation; T-Lymphocyte; absorption; airborne allergen; atopy; cytokine; improved; lymphocyte proliferation; prophylactic; respiratory; response

DESCRIPTION (provided by applicant): The overall goal of this project is to understand the atopic march and the role of the skin in this process of systemic allergen sensitization in children with atopic dermatitis (AD). Our overall hypothesis is that AD results in increased skin allergen absorption and systemic allergen sensitization reflected in high IgE levels. This makes patients with AD prone to the development of respiratory allergy (Atopic March). Improving skin barrier function with prophylactic topical pimecrolimus would reduce allergen absorption, allergen sensitization and reduce the prevalence of asthma. This would be evidenced by a decreased expression of cutaneous leukocyte antigen (CLA)+ TH2 cells in the pimecrolimus treated group. The clinical trial of pimecrolimus "A 3-year, randomized, double-blind vehicle controlled study to evaluate the safety and efficacy of Elidel 1% cream in modifying the course of AD in infants" is being supported by Novartis Pharmaceutical Co. provides an unique opportunity to study the mechanism of atopic dermatitis and the atopic march. Our proposed study has three aims in examining the atopic march and possible prevention. The first aim will examine specific and total allergen sensitization by allergen-specific and total IgE. The second aim will be examining mechanistic parts of this study. We will explore the frequency of skin homing T cells, their cytokine expression and the effect of staphylococcal superantigen on their expression. In third aim of the trial, we explore the effects of pimecrolimus as a disease-modifying agent in the prevention of asthma. Asthma phenotype will be examined by spirometry per and post-beta-2-agonist and exhaled nitric oxide.

描述（由申请人提供）：本项目的总体目标是了解特应性皮炎（AD）儿童的特应性进展和皮肤在全身过敏原致敏过程中的作用。我们的总体假设是，AD导致皮肤过敏原吸收增加和全身过敏原致敏反应，反映在高IgE水平。这使得AD患者容易发生呼吸道过敏（特应性进行曲）。预防性外用吡美莫司改善皮肤屏障功能可减少过敏原吸收、过敏原致敏并降低哮喘患病率。这将通过吡美莫司处理组中皮肤白细胞抗原（CLA）+TH 2细胞的表达降低来证明。诺华制药公司支持的吡美莫司临床试验“一项为期3年、随机、双盲、溶剂对照研究，旨在评价Elidel 1%乳膏在改变婴儿AD病程中的安全性和有效性”，为研究特应性皮炎和特应性进展的机制提供了一个独特的机会。我们提出的研究有三个目的，在检查特应性游行和可能的预防。第一个目标是通过过敏原特异性和总IgE检查特异性和总过敏原致敏性。第二个目标是检查本研究的机制部分。我们将探讨皮肤归巢T细胞的频率，它们的细胞因子表达和葡萄球菌超抗原对其表达的影响。在本试验的第三个目的中，我们探索吡美莫司作为疾病缓解剂在预防哮喘中的作用。哮喘表型将通过肺功能测定法和β-2-激动剂后和呼出的一氧化氮进行检查。