Corticosteroids inhibit the production of inflammatory mediators in immature monocyte-derived DC and induce the development of tolerogenic DC3

Corticosteroids (CS) are potent immunosuppressive agents that are known to affect T cell-mediated inflammation by the inhibition of proliferation and cytokine production, as well. as the immunostimulatory function of monocyte s and macrophages, Not much is known of the effect of corticosteroids on de ndritic cells (DC), the professional T cell stimulatory antigen-presenting cells. We report that the endogenous CS hydrocortisone and the synthetic CS clobetasol-17-propionate strongly inhibited the production of the inflamma tory mediators interleukin (IL)-12 p70, tumor necrosis factor alpha (TNF-al pha), and IL-6 by lipopolysaccharide (LPS)-stimulated monocyte-derived imma ture DC (iDC) in vitro, In contrast, the stimulatory capacity, antigen upta ke, and the expression of costimulatory molecules were not affected. In acc ordance with the decreased production of IL-12 p70, CS-treated iDC induced less production of the inflammatory Th1 cytokine interferon-gamma and enhan ced levels of the Th2 cytokines IL10 and IL-5 in staphylococcal enterotoxin B-stimulated CD4(+) Th cells, Furthermore, CS inhibited the maturation of iDC as assessed by the lack of expression of CD83 as well as by the prevent ion of the loss of antigen uptake capacities. These type 3 DC (DC3) matured in the presence of CS produce less IL-12 p70 and have a decreased T cell s timulatory capacity. Moreover, uncommitted T cells that encounter the CS-in duced DC3 develop into Th2-biased cells, which may additionally decrease th e Th1-mediated tissue damage but, on the other hand, Th2 cytokines may prom ote undesirable elevation of IgE and eosinophilia. These findings indicate that suppression of T cell-mediated inflammation by CS not only relies on d irect effects on T cells, but also on various effects on DC, their professi onal antigen-presenting cells.