Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells

Background: Dehydroepiandrosterone (DHEA) has been suggested as an immunost imulating steroid hormone, of which the effects on the development of dendr itic cells IDC) are unknown. The effects of DHEA often oppose those of the other adrenal glucocorticoid, cortisol, Glucocorticoids (GC) are known to s uppress the immune response at different levels and have recently been show n to modulate the development of DC, thereby influencing the initiation of the immune response. Variations in the duration of exposure to, and doses o f, GC (particularly dexamethasone (DEI)) however, have resulted in conflict ing effects on DC development. Aim: In this study, we describe the effects of a continuous high level of e xposure to the adrenal steroid DHEA (10(-6) M) on the generation of immatur e DC from monocytes, as well as the effects of the opposing steroid DEX on this development. Results: The continuous presence of DHEA (10(-6) M) in GM-CSF/IL-4-induced monocyte-derived DC cultures resulted in immature DC with a morphology and Functional capabilities similar to those of typical immature DC (T cell sti mulation, IL-12/IL-10 production), but with a slightly altered phenotype of increased CD80 and decreased CD43 expression (markers of maturity). The continuous presence of DEX at a concentration of 10(-6) hi in the monoc yte/DC cultures resulted in the generation of plastic-adherent macrophage-l ike cells in place of typical immature DC. with increased CD14 expression, but decreased expression of the typical DC markers CD1a, CD40 and CD80, The se cells were strongly reactive to acid phosphatase, but equally capable of stimulating T cell proliferation as immature DC. The production of IL-12, by these macrophage-like cells was virtually shut down, whereas the product ion of IL-10 was significantly higher than that of control immature DC. Conclusion: The continuous presence of a high level of GC during the genera tion of immature DC from monocytes can modulate this development away from DC towards a macrophage-like cell, The combination of a low CD80 expression and a shutdown of IL-12 production suggests the possibility of DEX-generat ed cells initiating a Th2-biased response. These effects by DEX on DC devel opment contrast with those by DHEA, which resulted in a more typical DC alt hough possessing a phenotype possibly indicating a more mature state of the cell.