Monokines mediate decreased hepatic glucocorticoid binding in endotoxemia.
The purpose of this study was to determine whether endotoxin decreased hepatic glucocorticoid binding by the action of mediator(s). Steroid binding in liver cytosol, plasma glucose levels, and plasma corticosterone levels were assayed in C3HeB/FeJ LPS normoresponsive and C3H/HeJ LPS hyporesponsive mice. In C3HeB/FeJ mice, endotoxin significantly depressed the maximum number of steroid binding sites (Bmax) to 30% of control. Plasma glucose levels were decreased to 50% of control, and plasma corticosterone levels increased 4-fold. No changes in these parameters were seen in C3H/HeJ mice given endotoxin, except for decreased plasma glucose levels at the highest dose of endotoxin. Decreased steroid binding was observed in C3H/HeJ mice 4-6 hours after receiving C3HeB/FeJ peritoneal exudate cells (elicited with thioglycolate) and endotoxin. No change in steroid binding was observed in C3H/HeJ mice that received C3H/HeJ peritoneal exudate cells and endotoxin. Mediator-rich plasma was produced in CF-1 mice by infecting them with 1 X 10(7) BCG and by challenging them with endotoxin (2 micrograms) 2 weeks later for 2 h. Transfer of BCG-endotoxin plasma to C3H/HeJ mice also resulted in decreased steroid binding and plasma glucose. These results indicate that perturbation of glucocorticoid action during endotoxin shock is mediated by soluble factor(s) other than endotoxin. A likely source of mediator(s) is the mononuclear phagocyte.
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D001427:Bacterial Toxins / Q000633:toxicity*; D001786:Blood Glucose / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003600:Cytosol / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D005938:Glucocorticoids / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008264:Macrophages / Q000637:transplantation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H / Q000276:immunology; D009000:Monocytes / Q000637:transplantation; D015846:Monokines; D009163:Mycobacterium bovis / Q000276:immunology; D011506:Proteins / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012486:Salmonella typhimurium
D001427:Bacterial Toxins; D001786:Blood Glucose; D004731:Endotoxins; D005938:Glucocorticoids; D015846:Monokines; D011506:Proteins; D011965:Receptors, Glucocorticoid; D003345:Corticosterone