DEHYDROEPIANDROSTERONE MODULATION OF LIPOPOLYSACCHARIDE-STIMULATED MONOCYTE CYTOTOXICITY

Dehydroepiandrosterone (DHEA), the predominant androgen secreted by th e adrenal cortex, can be converted to both potent androgens and estrog ens, In addition to its role as a precursor for other steroid hormones , DHEA has been proposed to play an important role in immunity, This s tudy has investigated DHEA modulation of LPS-induced monocyte cytotoxi city, Cytotoxicity markers assessed include tumor cell killing, IL-1 s ecretion, reactive oxygen intermediate release, nitric oxide synthetas e activity as measured by the release of reactive nitrogen intermediat es, complement receptor-1 cell surface protein, and TNF-alpha protein presence, Monocytes stimulated with LPS concentrations of 1.0 mu g/ml displayed the above cytotoxic markers, whereas monocytes stimulated wi th DHEA alone or with LPS at a lower concentration of 0.2 ng/ml did no t, However, when used simultaneously, DHEA and LPS 0.2 ng/ml displayed a synergistic effect on monocyte cytotoxicity against cancerous cell lines, IL-1 secretion, reactive nitrogen intermediate release, complem ent receptor-1 cell-surface protein, and TNF-alpha protein to levels c omparable with levels obtained using LPS 1.0 mu g/ml. Finally, Scatcha rd plot analysis demonstrated the presence of a DHEA receptor in monoc ytes, suggesting that DHEA effects on LPS-stimulated monocytes are med iated through a receptor-dependent process.