Interleukin-6 production does not increase with age

Investigators have reported an increase, decrease, or no effect of age on i nterleukin-6 (IL-6) production. Differences in experimental conditions and the health status of subjects may explain these contradicting results. Beca use the subjects used in most of the previous studies were not carefully sc reened for health, we investigated the effect of age on IL-6 production in healthy young and elderly subjects. Twenty young (aged 20-30 years) and 26 elderly (>65 years) men completed the study. Each subject was screened for good health, undergoing physical examinations and laboratory tests. Circula ting IL-6 levels were not significantly different between young and elderly subjects. A subgroup of subjects representing both young and elderly volun teers had high (>1000 pg/ml) circulating levels of IL-6, However, circulati ng IL-6 levels were low (<100 pg/ml) in the majority of subjects in both ag e groups. Peripheral blood mononuclear cells (PBMC) were cultured for IL-6 production in the presence or absence of phytohemagglutinin (PHA) or concan avalin (Con)A for 48 hours, Unstimulated secretion of IL-6 by PBMC cultured in autologous plasma (AP) or fetal bovine serum (FBS) was detectable in th e majority of cultures, Age did not influence this spontaneous secretion of IL-6, PBMC stimulation with PHA or ConA significantly increased IL-6 produ ction, but age did not affect the ability of PBMC to secrete IL-6 after sti mulation when cultured in FBS, IL-6 production by PBMC cultured in AP and s timulated with PHA was not affected by age. However, when stimulated with C onA, PBMC from the elderly subjects produced less IL-6 than PBMC from the y oung subjects. Because IL-6 has been suggested to contribute to the age-rel ated increase in prostaglandin (PG)E-2 and nitric oxide (NO) production, we investigated the effect of age on the production of IL-6 by murine periton eal macrophages (M<phi>) as well as the effect of IL-6 on the production of other M phi inflammatory products. Similar to the findings in humans, mous e age did not influence the level of IL-6 produced by M phi. These data sug gest that in healthy subjects, increased production of IL-6 is not a normal consequence of aging. Previously reported higher IL-6 levels in elderly su bjects might reflect an underlying, undiagnosed disease state. PGE(2) and N O production were not affected by the addition of IL-6 to M phi from young mice or anti-IL-6 antibody to M phi from old mice. Thus, IL-6 does not appe ar to influence the M phi production of selected inflammatory molecules.