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Original Studies |
Departments of Internal Medicine I (R.H.S., L.K., S.H., J.S., W.F., B.L.), Laboratory Medicine and Clinical Chemistry (G.R.), and Hematology and Oncology (M.K.), University Medical Center, D-93042 Regensburg, Germany
Address all correspondence and requests for reprints to: Dr. Rainer H. Straub, Laboratory of Neuroendocrinoimmunology, Department of Internal Medicine I, University Medical Center, D-93042 Regensburg, Germany. E-mail: rainer.straub{at}klinik.uni-regensburg.de
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-
, 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- 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 x 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.
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