Meng Q, Ying S, Corrigan C J, Wakelin M, Assoufi B, Moqbel R, Kay A B
Allergy and Clinical Immunology, Imperial College School of Medicine, National Heart and Lung Institute, London, UK.
Allergy. 1997 Nov;52(11):1095-101. doi: 10.1111/j.1398-9995.1997.tb00181.x.
Interleukin-5 (IL-5) enhances eosinophil degranulation and prolongs eosinophil survival. Rapamycin, cyclosporin A, and dexamethasone have been shown to influence either cytokine transcription, cytokine-mediated signalling, or degranulation by granulocytes. The study aimed to determine whether these agents inhibited IL-5-enhanced eosinophil survival or degranulation. Peripheral blood eosinophils were isolated from atopic subjects. The effects of serial dilutions (10(-6)-10(-9) M) of these drugs or vehicle control on 1) the viability of eosinophils cultured (1-5 days) in the presence and absence of recombinant human IL-5, as measured by propidium iodide staining and flow cytometry, and 2) degranulation of eosinophils preincubated (45 min) with rhIL-5 or medium control, as measured by eosinophil cationic protein (ECP) release after stimulation with serum-coated Sephadex beads, were assessed. Dexamethasone and rapamycin produced significant, concentration-dependent inhibition of IL-5-enhanced eosinophil survival at pharmacologic concentrations, whereas cyclosporin A did not. Prior incubation of eosinophils with IL-5, as compared with medium control, significantly enhanced ECP release by eosinophils on subsequent exposure to serum-coated Sephadex beads. Cyclosporin A and rapamycin significantly inhibited IL-5-enhanced ECP release in a concentration-dependent fashion, whereas dexamethasone did not. All three drugs had no significant effect on eosinophil survival and degranulation in the absence of IL-5. Our results suggest that immunosuppressive drugs may inhibit IL-5-mediated mechanisms in eosinophils which result in enhanced survival and release of granule contents. These findings may be relevant to the further development of therapeutic strategies in allergic diseases.
白细胞介素-5（IL-5）可增强嗜酸性粒细胞脱颗粒并延长其存活时间。雷帕霉素、环孢素A和地塞米松已被证明会影响细胞因子转录、细胞因子介导的信号传导或粒细胞的脱颗粒。该研究旨在确定这些药物是否能抑制IL-5增强的嗜酸性粒细胞存活或脱颗粒。从特应性受试者中分离出外周血嗜酸性粒细胞。通过碘化丙啶染色和流式细胞术测量，评估这些药物或溶剂对照的系列稀释液（10⁻⁶ - 10⁻⁹ M）对1）在有和无重组人IL-5存在的情况下培养（1 - 5天）的嗜酸性粒细胞活力的影响，以及2）用血清包被的葡聚糖凝胶珠刺激后，通过嗜酸性粒细胞阳离子蛋白（ECP）释放来测量，对预先用rhIL-5或培养基对照预孵育（45分钟）的嗜酸性粒细胞脱颗粒的影响。地塞米松和雷帕霉素在药理浓度下对IL-5增强的嗜酸性粒细胞存活产生显著的、浓度依赖性抑制，而环孢素A则没有。与培养基对照相比，用IL-5预先孵育嗜酸性粒细胞，在随后暴露于血清包被的葡聚糖凝胶珠时，显著增强了嗜酸性粒细胞的ECP释放。环孢素A和雷帕霉素以浓度依赖性方式显著抑制IL-5增强的ECP释放，而地塞米松则没有。在没有IL-5的情况下，所有三种药物对嗜酸性粒细胞存活和脱颗粒均无显著影响。我们的结果表明，免疫抑制药物可能抑制嗜酸性粒细胞中IL-5介导的机制，这些机制导致存活增强和颗粒内容物释放。这些发现可能与过敏性疾病治疗策略的进一步发展相关。
