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 regulated, 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 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-1beta and IL-1 receptor antagonist was inhibited in a dose-dependent manner (P = 0.001) without age- or gender-related differences. Hydrocortisone decreased soluble IL-1 receptor type II (sIL-1RII) secretion by unstimulated cells (P = 0. 0001), but it increased secretion by LPS-stimulated cells (P = 0. 0001) in all groups. Unstimulated cell supernatants from men contained greater concentrations of sIL-1RII than the supernatants from women (P = 0.011). Compared with men, PBMCs from women were less responsive to hydrocortisone inhibition of sIL-1RII secretion, regardless of age (P = 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.
Daun
J M
JM
Intercollege Physiology Program, Noll Physiological Research Center, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Ball
R W
RW
Cannon
J G
JG
D000328:Adult; D000367:Age Factors; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D005498:Follicular Phase / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008183:Luteal Phase / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017472:Receptors, Interleukin-1 / Q000097:blood; D053574:Receptors, Interleukin-1 Type II; D012737:Sex Factors; D012795:Sialoglycoproteins / Q000097:blood / Q000378:metabolism*; D012995:Solubility
D000893:Anti-Inflammatory Agents; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D012795:Sialoglycoproteins; D006854:Hydrocortisone