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.
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-alpha, 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-alpha 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.
Straub
R H
RH
Department of Internal Medicine I, University Medical Center, Regensburg, Germany. rainer.straub@klinik.uni-regensburg.de
Konecna
L
L
Hrach
S
S
Rothe
G
G
Kreutz
M
M
Schölmerich
J
J
Falk
W
W
Lang
B
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000735:Androstenedione / Q000097:blood; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000097:blood* / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate