Corticosteroid modulation of human, antigen-specific Th1 and Th2 responses.
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 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 toxoid 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; 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 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.
Braun
C M
CM
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md, USA.
Huang
S K
SK
Bashian
G G
GG
Kagey-Sobotka
A
A
Lichtenstein
L M
LM
Essayan
D M
DM
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D017951:Antigen Presentation; D019819:Budesonide; D002455:Cell Division; D002478:Cells, Cultured; D002999:Clone Cells; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011058:Pollen / Q000276:immunology; D011282:Pregnenediones / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000276:immunology*; D012882:Skin Tests; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D018793:Interleukin-13; D015848:Interleukin-5; D011282:Pregnenediones; D015847:Interleukin-4; D019819:Budesonide; D003907:Dexamethasone; D007371:Interferon-gamma; D006854:Hydrocortisone