ALTERED REGULATION OF IL-6 PRODUCTION WITH NORMAL AGING - POSSIBLE LINKAGE TO THE AGE-ASSOCIATED DECLINE IN DEHYDROEPIANDROSTERONE AND ITS SULFATED DERIVATIVE

Normal aging in humans has been recently shown to be accompanied by re duced control over production of the multifunctional cytokine IL-6. Th is cytokine was reported to be quantitatively elevated in most serum s amples obtained from ''normal'' elderly humans. In the present investi gation, we report that IL-6 levels are elevated in serum samples obtai ned from aged mice, and its spontaneous production could also be easil y detected in culture supernatants of unstimulated lymphoid cells obta ined from aged, but not mature, adult donors. Spontaneous production o f IL-6 was consistently observed in culture supernatants of lymphoid c ells from both the spleen and mesenteric lymph nodes from aged donors, but was absent from supernatants derived from their peripheral lymph nodes. In aged mice, the reduced regulation of IL-6 production could b e effectively prevented and/or reversed by supplementing aging animals with dehydroepiandrosterone sulfate, a steroid hormone whose endogeno us production is known to decline with advancing age in all species te sted. It was also established that serum obtained from old dehydroepia ndrosterone sulfate-treated mice contained lower (normal) levels of se rum amyloid P substance (an acute phase reactant), reduced levels of s erum Ig (all classes and isotypes) and lower titers of tissue-specific autoantibodies than untreated aged controls. Therefore, a number of w ell described, age-related conditions, some of which could be contribu ting to the pathologic phenotype of old age, may actually represent se condary effects to this age-associated change in IL-6 production.