Corticosteroid modulation of human, antigen-specific Th1 and Th2 responses
Corticosteroid modulation of human, antigen-specific Th1 and Th2 responses
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DOI：
10.1016/s0091-6749(97)70255-0
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发表时间：
1997-09-01
影响因子：
14.2
通讯作者：
Essayan, DM
中科院分区：
文献类型：
--
作者：
Braun, CM;Huang, SK;Essayan, DM
皮质类固醇是调节人T淋巴细胞应答的强效促炎剂。关于它们对Th 1和Th 2亚群可能的不同影响仍存在争议。本研究探讨了这些药物在人，抗原驱动的外周血单核细胞（PBMC）和非转化，抗原特异性的Th 1和Th 2克隆的动力学和疗效。来自双重致敏个体的豚草和破伤风类毒素驱动的PBMC增殖反应被地塞米松同等地下调（50%抑制浓度[IC 50]分别为3 x 10（-9）和2 x 10（-9）mol/L）。迟至豚草刺激后36小时添加地塞米松仍然导致超过75%的增殖反应抑制，而地塞米松的功效小于50%时，破伤风环刺激后24小时添加。地塞米松还下调了PBMC中促炎细胞因子（IL-4、IL-5、IL-13和干扰素-γ）的抗原诱导基因表达。几种皮质类固醇激素（氢化可的松<布地奈德<地塞米松; IC_（50）= 10（-6）~ 10（-8）mol/L）可抑制抗原特异性Th 1和Th 2克隆的增殖，但Th 1和Th 2克隆之间无明显差异。克隆中的IC 50值比PBMC中的IC 50值高10倍。IL-4、IL-13和干扰素-γ的基因表达和蛋白分泌以浓度依赖性方式被Th 1和Th 2克隆中的每种皮质类固醇下调。这些数据表明，Th 1和Th 2反应同样受到皮质类固醇的影响。
Corticosteroids are potent antiinflammatory agents that modulate human T-lymphocyte responses. Controversy remains as to their possible differential effects on Th1 and Th2 subsets. This study explores the kinetics and efficacy of these agents in human, antigen-driven peripheral blood mononuclear cells (PBMCs) and in nontransformed, antigen-specific Th1 and Th2 clones. Ragweed-and tetanus toxoid-driven proliferative responses of PBMCs from dually sensitized individuals were downregulated equally by dexamethasone (inhibitory concentration of 50% [IC50] = 3 x 10(-9) and 2 x 10(-9) mol/L, respectively). The addition of dexamethasone as late as 36 hours after ragweed stimulation still resulted in more than 75% inhibition of the proliferative response, whereas the efficacy of dexamethasone was less than 50% when added 24 hours after tetanus toroid stimulation. Antigen-induced gene expression for proinflammatory cytokines (IL-4, IL-5, IL-13, and interferon-gamma) from PBMCs was also downregulated by dexamethasone. Proliferation of antigen-specific Th1 and Th2 clones was inhibited by several corticosteroids (hydrocortisone < budesonide < dexamethasone; IC50 = 10(-6) to 10(-8) mol/L), but no significant differences between Th1 and Th2 clones were evident. IC50 values in the clones were 10-fold greater than in PBMCs. Gene expression and protein secretion for IL-4, IL-13, and interferon-gamma were downregulated in a concentration-dependent manner by each of the corticosteroids in Th1 and Th2 clones. These data suggest that Th1 and Th2 responses are equally affected by corticosteroids.