Corticosteroids inhibit IL-12 production in human monocytes and enhance their capacity to induce IL-4 synthesis in CD4+ lymphocytes.
We examined the effects of corticosteroids on IL-12 production by human monocytes and on cytokine synthesis in T cells. To distinguish the effects of corticosteroids on the APC used to activate the T cell from direct effects of corticosteroids on the T cell, experiments were performed by exposing the APC and not the T cell to corticosteroids. We found that corticosteroids significantly inhibited the production in monocytes of IL-12, a cytokine that is extremely potent in enhancing IFN-gamma and inhibiting IL-4 synthesis in T cells. We demonstrated that reduced production of IL-12 in corticosteroid-treated monocytes resulted in a decreased capacity of the monocytes to induce IFN-gamma and an increased ability to induce IL-4 in T cells. These results suggest that although corticosteroids may be beneficial for the treatment of asthma or allergic disease due to direct inhibitory effects of corticosteroids on cytokine synthesis in T cells, chronic corticosteroid therapy may indirectly exacerbate the long-term course of allergic disease. This deleterious effect of corticosteroids would result from a limitation in IL-12 production in tissue monocytes and macrophages, which would enhance production of Th2 cytokines (which augment allergic disease), and would reduce production of Th1 cytokines (which attenuate allergic disease) in T cells that subsequently infiltrate the tissues.
Blotta
M H
MH
Department of Pediatrics, Stanford University, CA 94305, USA.
DeKruyff
R H
RH
Umetsu
D T
DT
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*
D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D003907:Dexamethasone; D007371:Interferon-gamma