Corticosteroid modulation of human, antigen-specific Th1 and Th2 responses

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:100

Article

Braun, CM ; Huang, SK ; Bashian, GG ; KageySobotka, A ; Lichtenstein, LM ; Essayan, DM

关键词: human;    Th1/Th2;    IL-4;    IL-13;    interferon-gamma;    corticosteroids;   

DOI  :  10.1016/S0091-6749(97)70255-0

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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