title: Androgen-replacement therapy depresses the ex vivo production of inflammatory cytokines by circulating antigen-presenting cells in aging type-2 diabetic men with partial androgen deficiency.
abstract: Androgens are considered to have immunomodulatory effects but their cellular mechanisms of action remain largely unknown. In the present study we prospectively analyzed the serial effects of androgen-replacement therapy on both the distribution of peripheral blood lymphocytes, monocytes and dendritic cells as well as on the production of interleukin (IL)-1beta, IL-6 and tumor necrosis factor alpha (TNFalpha) inflammatory cytokines by circulating monocytes and CD33 myeloid, CD16 and plasmacytoid dendritic cell subsets, the most potent antigen-presenting cells (APCs) in type-2 diabetic men with partial androgen deficiency. Analyses were performed before therapy and at 1, 3, 6 and 12 months after treatment with 150 mg testosterone enanthate every 2 weeks in a group of 13 type-2 diabetic men. Our results show for the first time that testosterone-replacement therapy is associated with a reduction or complete abrogation of spontaneous ex vivo production of IL-1beta, IL-6 and TNFalpha by APCs. Meanwhile, the in vitro production of inflammatory cytokines by these cells after stimulation with lipopolysaccharide plus recombinant human interferon-gamma remained unchanged, suggesting that APCs preserve their constitutive machinery to produce inflammatory cytokines under androgen treatment. These results confirm and extend previous observations about the anti-inflammatory effects of androgen therapy on APCs in a new, previously unexplored model of androgen deficiency; namely, aging type-2 diabetic men. A decreased production of inflammatory cytokines by APCs might have important consequences for sex differences in susceptibility to autoimmune diseases, inflammatory response to injury and atheromatosis.
authors.affiliation: Servicio de Endocrinología, Hospital Universitario de Salamanca, Paseo de San Vicente 58-182, 37007 Salamanca, Spain. corrales@usal.es
authors.forename: J J
authors.initials: JJ
authors.lastname: Corrales
authors.forename: M
authors.initials: M
authors.lastname: Almeida
authors.forename: R
authors.initials: R
authors.lastname: Burgo
authors.forename: M T
authors.initials: MT
authors.lastname: Mories
authors.forename: J M
authors.initials: JM
authors.lastname: Miralles
authors.forename: A
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000368:Aged; D000728:Androgens / Q000172:deficiency* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D003864:Depression, Chemical; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D020249:Hormone Replacement Therapy; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000728:Androgens; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D013739:Testosterone