Serum Dehydroepiandrosterone (DHEA) and DHEA Sulfate Are Negatively Correlated with Serum Interleukin-6 (IL-6), and DHEA Inhibits IL-6 Secretion from Mononuclear Cells in Man in Vitro: Possible Link between Endocrinosenescence and Immunosenescence

• Published in: The journal of clinical endocrinology and metabolism Vol. 83; no. 6; pp. 2012 - 2017
• Main Authors: Straub, R. H., Konecna, L., Hrach, S., Rothe, G., Kreutz, M., Schölmerich, J., Falk, W., Lang, B.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.06.1998; Endocrine Society
• Subjects: Adolescent; Adult; Age; Aged; Aged, 80 and over; Aging; Aging - physiology; Androstenedione; Androstenedione - blood; Arteriosclerosis; Biological and medical sciences; Blood levels; Cells, Cultured; Cytokines; Dehydroepiandrosterone; Dehydroepiandrosterone - blood; Dehydroepiandrosterone - pharmacology; Dehydroepiandrosterone sulfate; Dehydroepiandrosterone Sulfate - blood; Development. Metamorphosis. Moult. Ageing; Female; Fundamental and applied biological sciences. Psychology; Humans; Immunomodulation; Immunosenescence; Interleukin 2; Interleukin 6; Interleukin-6 - blood; Interleukin-6 - secretion; Leukocytes (mononuclear); Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Male; Middle Aged; Osteoporosis; Peripheral blood mononuclear cells; Rheumatoid arthritis; Serum levels; Sex hormones; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Europe; Germany; Human; Cell culture; Androgen; Cytokine; Sex; Male; Blood plasma; Assay; Interleukin 6; Dehydroepiandrosterone; Dehydroepiandrosterone sulfate; Mononuclear cell; Adolescent; Adult; Female; Biological effect; Hormonal investigation; Sex steroid hormone; Elderly; Age; Comparative study
• DOI: 10.1210/jcem.83.6.4876
• ISSN: 0021-972X

Interleukin-6 (IL-6) is one of the pathogenetic elements in inflammatory and age-related diseases such as rheumatoid arthritis, osteoporosis, atherosclerosis, and late-onset B cell neoplasia. In these diseases or during aging, the decrease in production of sex hormones such as dehydroepiandrosterone (DHEA) is thought to play an important role in IL-6-mediated pathogenetic effects in mice. In humans, we investigated the correlation of serum levels of DHEA, DHEA sulfate (DHEAS), or androstenedione (ASD) and IL-6, tumor necrosis factor-α, or IL-2 with age in 120 female and male healthy subjects (15–75 yr of age). Serum DHEA, DHEAS, and ASD levels significantly decreased with age (all P < 0.001), whereas serum IL-6 levels significantly increased with age (P < 0.001). DHEA/DHEAS and IL-6 (but not tumor necrosis factor-α or IL-2) were inversely correlated (all patients: r = −0.242/−0.312; P = 0.010/0.001). In female and male subjects, DHEA and ASD concentration dependently inhibited IL-6 production from peripheral blood mononuclear cells (P = 0.001). The concentration-response curve for DHEA was U shaped (maximal effective concentration, 1–5 × 10−8 mol/L), which may be the optimal range for immunomodulation. In summary, the data indicate a functional link between DHEA or ASD and IL-6. It is concluded that the increase in IL-6 production during the process of aging might be due to diminished DHEA and ASD secretion. Immunosenescence may be directly related to endocrinosenescence, which, in turn, may be a significant cofactor for the manifestation of inflammatory and age-related diseases.