Glucocorticoid sensitivity of interleukin-1 agonist and antagonist secretion: the effects of age and gender

Interleukin-1 (IL-1) is a primary mediator of inflammation that is regulate d, in part, by the hypothalamic-pituitary-adrenal axis. The purpose of this study was to determine if gender- or age-related differences exist in the sensitivity of IL-1-producing cells to hydrocortisone. Peripheral blood mon onuclear cells (PBMC) isolated from men and women (21-77 yr old) were incub ated with hydrocortisone (0, 50, 100, 500, or 1,000 ng/ml) with or without lipopolysaccharide (LPS). Secretion of IL-1 beta and IL-1 receptor antagoni st was inhibited in a dose-dependent manner (P = 0.001) without age- or gen der-related differences. Hydrocortisone decreased soluble IL-1 receptor typ e II (sIL-1RII) secretion by unstimulated cells (P = 0.0001), but it increa sed secretion by LPS-stimulated cells (P = 0.0001) in all groups. Unstimula ted cell supernatants from men contained greater concentrations of sIL-1RII than the supernatants from women (P = 0.011). Compared with men, PBMCs fro m women were less responsive to hydrocortisone inhibition of sIL-1RII secre tion, regardless of age (P = 0.001), and compared with the follicular phase , sUI-1RII secretion was lower in the luteal phase of the menstrual cycle ( P < 0.05). These data indicate that basal secretion and glucocorticoid modu lation of sIL-1RII secretion by cultured PBMCs are gender dependent. Moreov er, glucocorticoid influences on sIL-1RII secretion depend on the presence or absence of gram-negative bacterial toxins.