Soluble receptors and other substances that regulate proinflammatory cytokines in young and aging humans

Relatively little is known about changes in soluble receptors and other ago nists/antagonists that may regulate cytokine actions in aging humans. We ha ve studied age-associated changes in human subjects of (a) the plasma level s of interleukin-l soluble receptor (IL-1sRII), interleukin-l receptor anta gonist (IL-1ra), tumor necrosis factor soluble receptor-II (75kDa; TNFsRII) , and interleukin-6 soluble receptor (IL-6sR) and (b) the ability of their blood mononuclear cells to produce those soluble factors spontaneously and after phytohemagglutinin (PHA) stimulation. Aging subjects (50-67 years) ha d significantly higher plasma levels of IL-1ra, significantly lower levels of TNFsRII and IL-6sR than young subjects (25-35 years), and no significant change in the level of IL-1sRII. There was less spontaneous output of IL-1 ra and TNFsRII by peripheral blood mononuclear cells (PBMC) of aging than o f young subjects, but equivalent output of both factors in response to PHA stimulation. Thus, the basal (homeostatic) output of those two factors decl ined with age, but the potential of the PBMC to produce the factors on stim ulation did not. PHA stimulation of PBMC of either age group significantly inhibited the output of IL-6sR. These differences between the young adult a nd aging subjects, along with reported changes in the corresponding cytokin es, presumably foreshadow changes that become more marked with further agin g. Therefore, immunological processes that depend on, or are modulated by, proinflammatory cytokines may differ between young and aged subjects as a c onsequence of the availability of regulatory soluble receptors and related agonists or antagonists. The results of this study highlight the need for f urther studies of the roles played by soluble receptors, and similar agonis ts/antagonists, in the immune responses of aged adults.