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
Open accessAbstract
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)-1β, IL-6 and tumor necrosis factor α (TNFα) 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-1β, IL-6 and TNFα by APCs. Meanwhile, the in vitro production of inflammatory cytokines by these cells after stimulation with lipopolysaccharide plus recombinant human interferon-γ 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.
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Reductions in TNF and IL-6 in older men with hypogonadism can be reversed by testosterone treatment.
“However, reductions in TNF and IL-6 observed in older men with hypogonadism can be reversed following testosterone treatment406.”
From Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies (2018) · cites this paper as [406]
The Discussion says acute hypogonadism in elderly men increased circulating TNF and IL-6, rather than reducing them; subsequent testosterone treatment reduced TNF but not IL-6. The Results report that testosterone treatment suppressed spontaneous ex vivo production of both cytokines in the paper’s older diabetic men, not that it reversed reductions in them. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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- Authors
- Corrales, J. J., Almeida, M., Burgo, R., Mories, M. T., Miralles, J. M., & Orfao, A.
- Affiliations
- Universidad de Salamanca (ES)
- Complejo Hospitalario de Salamanca (ES)
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2006-06
- Volume
- 189
- Issue
- 3
- Pages
- 595-604
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2139503270
- Cited by
- 110
- References
- 56
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 7 · 2021: 6 · 2020: 8 · 2019: 4 · 2018: 9 · 2017: 5 · 2016: 3 · 2015: 6 · 2014: 5 · 2013: 6 · 2012: 8
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- testosterone replacement therapy, testosterone enanthate, androgen deficiency, type 2 diabetes, older men, antigen-presenting cells, dendritic cells, monocytes, inflammatory cytokines, IL-1β, interleukin-6, TNF-α, immunomodulation, atheromatosis
- MeSH terms
- Aged, Androgens, Anti-Inflammatory Agents, Antigen-Presenting Cells, Depression, Chemical, Diabetes Mellitus, Type 2, Humans, Interleukin-1, Lymphocytes, Male, Middle Aged, Testosterone, Tumor Necrosis Factor-alpha, Interleukin-6, Case-Control Studies, Lymphocyte Subsets, Cytokines, Lymphocyte Count, Statistics, Nonparametric, Hormone Replacement Therapy
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