AREGU April 47/4

Daun, Jane M., Richard W. Ball, and Joseph G. Cannon. Glucocorticoid sensitivity of interleukin-1 agonist and antagonist secretion: the effects of age and gender. Am J Physiol Regulatory Integrative Comp Physiol 278: R855– R862, 2000.—Interleukin-1 (IL-1) is a primary mediator of inflammation that is regulated, in part, by the hypothalamicpituitary-adrenal axis. The purpose of this study was to determine if genderor age-related differences exist in the sensitivity of IL-1-producing cells to hydrocortisone. Peripheral blood mononuclear cells (PBMC) isolated from men and women (21–77 yr old) were incubated with hydrocortisone (0, 50, 100, 500, or 1,000 ng/ml) with or without lipopolysaccharide (LPS). Secretion of IL-1b and IL-1 receptor antagonist was inhibited in a dose-dependent manner (P 5 0.001) without ageor gender-related differences. Hydrocortisone decreased soluble IL-1 receptor type II (sIL-1RII) secretion by unstimulated cells (P 5 0.0001), but it increased secretion by LPS-stimulated cells (P 5 0.0001) in all groups. Unstimulated cell supernatants from men contained greater concentrations of sIL-1RII than the supernatants from women (P 5 0.011). Compared with men, PBMCs from women were less responsive to hydrocortisone inhibition of sIL-1RII secretion, regardless of age (P 5 0.001), and compared with the follicular phase, sIL-1RII secretion was lower in the luteal phase of the menstrual cycle (P , 0.05). These data indicate that basal secretion and glucocorticoid modulation of sIL-1RII secretion by cultured PBMCs are gender dependent. Moreover, glucocorticoid influences on sIL-1RII secretion depend on the presence or absence of gram-negative bacterial toxins.