title: Immunomodulatory effects of testosterone evaluated in all-trans retinoic acid differentiated HL-60 cells, granulocytes, and monocytes.
abstract: The sex hormones are known to affect innate immunity in humans. In this study we evaluated the immunomodulatory effects of testosterone in a model system comprising of all-trans retinoic acid differentiated HL-60 cells, and confirmed the results in human granulocytes and monocytes. Results showed that testosterone at pharmacological doses reduced the production of interleukin-8 and reactive oxygen species from differentiated HL-60 cells in a concentration dependent manner without affecting phagocytosis. The cells were stimulated with zymosan, lipopolysaccharide, or Bacillus subtilis. At the highest concentration of testosterone (120 μM), interleukin-8 secretion was reduced 42-80%, and production of reactive oxygen species was reduced 32-46%. Flutamide, an antagonist of the classical intracellular androgen receptor, was unable to antagonize the immunosuppressive effect of testosterone. We further demonstrated that the suppressive effect of testosterone has a short onset time. Our results suggest that testosterone affects the fast operating membrane bound androgen receptor or a rapid acting enzyme system. Testosterone, at pharmacological doses, was also shown to suppress generation of reactive oxygen species and interleukin-8 in human granulocytes and monocytes, respectively, to a similar extent as observed in differentiated HL-60 cells.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Alex
authors.initials: A
authors.lastname: Boje
authors.forename: Lise
authors.initials: L
authors.lastname: Moesby
authors.forename: Michael
authors.initials: M
authors.lastname: Timm
authors.forename: Erik W
authors.initials: EW
authors.lastname: Hansen
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D006098:Granulocytes / Q000187:drug effects* / Q000276:immunology; D018922:HL-60 Cells; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D016209:Interleukin-8 / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology; D013739:Testosterone / Q000494:pharmacology*; D014212:Tretinoin
chemical_list: D007155:Immunologic Factors; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D013739:Testosterone; D014212:Tretinoin