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

Abstract 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% [IC 50 ] = 3 × 10 –9 and 2 × 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 toxoid stimulation. Antigen-induced gene expression for proinflammatory cytokines (IL-4, IL-5, IL-13, and interferon-γ) from PBMCs was also downregulated by dexamethasone. Proliferation of antigen-specific Th1 and Th2 clones was inhibited by several corticosteroids (hydrocortisone < budesonide < dexamethasone; IC 50 = 10 –6 to 10 –8 mol/L), but no significant differences between Th1 and Th2 clones were evident. IC 50 values in the clones were 10-fold greater than in PBMCs. Gene expres-sion and protein secretion for IL-4, IL-13, and interferon-γ 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. (J Allergy CLin Immunol 1997;100:400-7.)