Activation of human monocytes by LPS and DHEA

Dehydroepiandrosterone (DHEA) alone, whatever the concentration used, or lipopolysaccharide (LPS) alone at 0.2 ng/ml did not induce the release of interleukin-6 (IL-6) or tumor necrosis factor (TNF) by human monocytes, However DHEA (10(-9) M or 10(-12) M) in association with LPS (0.2 ng/ml) did induce the release of IL-6 and TNF, When human monocytes were activated by 1 mu g/ml LPS, both IL-6 and TNF secretions were observed, Monocytes activated by both DHEA (10(-9) M or 10(-12) M) and LPS (1 mu g/ml) secreted IL-6 and TNF at a higher level than that observed for monocytes activated only by LPS (1 mu g/ml) alone, DHEA alone, whatever the concentration used, or LPS alone at 0.2 ng/ml did not induce the activation of mitogen-activated protein kinases (MAPkinases) and protein kinase C (PKC) or the expression of c-fos and c-jun. However DHEA (10(-9) M or 10(-12) M) and 0.2 ng/ml LPS together induced the activation of both MAPKinases and PKC and the expression of c-fos and c-jun, Furthermore, the activation of PKC and MAPKinases and the expression of c-fos and c-jun were much greater when human monocytes were activated by both LPS (1 mu g/ml) and DHEA (10(-9) M or 10(-12) M) than when the monocytes were activated only by LPS at 1 mu g/ml. Therefore, DHEA and LPS displayed a synergistic effect on monocyte activation.