IL-5 production by CD4+ T cells of asthmatic patients is suppressed by glucocorticoids and the immunosuppressants FK506 and cyclosporin A.
IL-5 production by CD4+ T cells of asthmatic patients is suppressed by glucocorticoids and the immunosuppressants FK506 and cyclosporin A.
复制标题
哮喘患者 CD4 T 细胞产生的 IL-5 受到糖皮质激素、免疫抑制剂 FK506 和环孢菌素 A 的抑制。
作者：
A. Mori;M. Suko;Y. Nishizaki;O. Kaminuma;S. Kobayashi;G. Matsuzaki;K. Yamamoto;K. Ito;N. Tsuruoka;H. Okudaira
尘螨敏感型特应症患者外周血单个核细胞(PBMC)在体外经特定变应原刺激后产生IL-5，而健康对照PBMC基本不产生IL-5。佛波酯和钙离子载体联合刺激诱导特应性和非特应性哮喘患者PBMC产生显著的IL-5，提示蛋白激酶C和钙离子内流都是产生IL-5所必需的。携带CD2或CD4的细胞耗尽几乎完全消除了产生IL-5的细胞，而携带CD8的细胞耗尽则相当丰富了它们。提示CD4+T细胞是外周血单核细胞产生IL-5的主要来源。比较特应性哮喘患者、非特应性哮喘患者和健康对照组PBMC产生IL-2、IL-4、IL-5和干扰素-γ的能力，发现除IL-5外，其他细胞因子的产生能力在三组间无显著差异。地塞米松、FK506和环孢素A在体外以剂量依赖的方式抑制IL-5的产生。FK506对IL-5基因表达也有明显的剂量依赖性抑制作用。吸入糖皮质激素(二丙酸倍氯米松)可明显改善哮喘患者的临床症状，改善肺功能，显著抑制PBMC产生IL-5，提示IL-5在哮喘发病机制中的重要作用及其调节的临床意义。
IL-5 was produced in vitro by peripheral blood mononuclear cells (PBMC) of mite-sensitive atopic patients upon challenge with specific allergen, while PBMC of healthy controls produced essentially no IL-5. Stimuli delivered by the combination of phorbol ester and Ca2+ ionophore induced marked IL-5 production by PBMC obtained from atopic and non-atopic asthmatics, suggesting that both protein kinase C and Ca2+ influx are required for IL-5 production. CD2- or CD4-bearing cell depletion almost completely removed IL-5-producing cells while CD8-bearing cell depletion rather enriched them. These findings indicate that CD4+ T cells are the principal source of IL-5 in PBMC. The capacity of PBMC of atopic asthmatics, non-atopic asthmatics and healthy controls to produce IL-2, IL-4, IL-5 and IFN-gamma was compared, to find that cytokine-producing capacities other than that of IL-5 (IL-2, IL-4 and IFN-gamma) were not significantly different among the three groups. Dexamethasone, FK506 and cyclosporin A suppressed IL-5 production in vitro in a dose-dependent manner. Clear dose-dependent suppression of IL-5 gene expression by FK506 was also observed. Treatment of asthmatic patients with inhaled glucocorticoid (beclomethasone dipropionate) ameliorated clinical symptoms, improved lung function and markedly suppressed IL-5 production by PBMC, suggesting the essential role of IL-5 in the pathogenesis of bronchial asthma and the clinical importance of its regulation.