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

J Endocrinol. 2006 Jun;189(3):595-604. doi: 10.1677/joe.1.06779.

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.

MeSH terms

  • Aged
  • Androgens / deficiency*
  • Androgens / therapeutic use
  • Anti-Inflammatory Agents / therapeutic use*
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism*
  • Case-Control Studies
  • Cytokines / metabolism*
  • Depression, Chemical
  • Diabetes Mellitus, Type 2 / immunology*
  • Hormone Replacement Therapy*
  • Humans
  • Interleukin-1 / immunology
  • Interleukin-6 / immunology
  • Lymphocyte Count
  • Lymphocyte Subsets / immunology
  • Lymphocytes / immunology
  • Male
  • Middle Aged
  • Statistics, Nonparametric
  • Testosterone / therapeutic use
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Androgens
  • Anti-Inflammatory Agents
  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Testosterone