title: Dehydroepiandrosterone modulation of lipopolysaccharide-stimulated monocyte cytotoxicity.
abstract: Dehydroepiandrosterone (DHEA), the predominant androgen secreted by the adrenal cortex, can be converted to both potent androgens and estrogens. In addition to its role as a precursor for other steroid hormones, DHEA has been proposed to play an important role in immunity. This study has investigated DHEA modulation of LPS-induced monocyte cytotoxicity. Cytotoxicity markers assessed include tumor cell killing, IL-1 secretion, reactive oxygen intermediate release, nitric oxide synthetase activity as measured by the release of reactive nitrogen intermediates, complement receptor-1 cell surface protein, and TNF-alpha protein presence. Monocytes stimulated with LPS concentrations of 1.0 micrograms/ml displayed the above cytotoxic markers, whereas monocytes stimulated with DHEA alone or with LPS at a lower concentration of 0.2 ng/ml did not. 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, complement receptor-1 cell-surface protein, and TNF-alpha protein to levels comparable with levels obtained using LPS 1.0 microgram/ml. Finally, Scatchard plot analysis demonstrated the presence of a DHEA receptor in monocytes, suggesting that DHEA effects on LPS-stimulated monocytes are mediated through a receptor-dependent process.
authors.affiliation: Department of Molecular Pharmacology and Biologic Chemistry, Northwestern University Medical School, Chicago, IL 60611, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: McLachlan
authors.forename: C D
authors.initials: CD
authors.lastname: Serkin
authors.forename: O
authors.initials: O
authors.lastname: Bakouche
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003687:Dehydroepiandrosterone / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism / Q000633:toxicity; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009573:Nitrites / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism; D017463:Receptors, Complement 3b / Q000096:biosynthesis; D011987:Receptors, Steroid / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D007106:Immune Sera; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009573:Nitrites; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D011987:Receptors, Steroid; D014409:Tumor Necrosis Factor-alpha; C095972:dehydroepiandrosterone receptor; D003687:Dehydroepiandrosterone