The in vivo effect of interleukin-1 beta on urea synthesis is mediated by glucocorticoids in rats.
Interleukin-1 beta has been proposed as one mediator of parts of the catabolic response following surgery. However, it is not known whether such an effect is due to interleukin-1 beta itself or the associated changes in glucocorticoids. The effect of interleukin-1 beta on urea synthesis was investigated in rats given a high (10 micrograms kg-1) and a low dose (0.1 microgram kg-1) of recombinant interleukin-1 beta (NOVO, Denmark) 3 h prior to determination of the rate of urea synthesis in vivo. Urea synthesis increased dose-dependently after the low dose from 4.0 +/- 0.3 (control) to 6.3 +/- 0.3 (P < 0.01), and after the high dose to 7.7 +/- 0.3 mumol (min.100 gBW)-1 (P < 0.01). The blood concentration of amino acids fell during interleukin-1 beta treatment, so the effect on urea synthesis was not due solely to increased proteolysis, but was exerted predominantly in the liver. Pharmacological glucocorticoid receptor blockade (hormone analogue RU486, Roussel-Uclaf, Paris, France) given 1 h prior to the interleukin treatment, completely abolished the interleukin-1 beta induced increases in urea synthesis. The study demonstrates that interleukin-1 beta stimulates urea synthesis in vivo, and that the major part of the effect depends on glucocorticoid action.
Department of Gastrointestinal Surgery C, Rigshospitalet, Copenhagen, Denmark.
H
H
Heindorff
T
T
Almdal
H
H
Vilstrup
D000596:Amino Acids / Q000097:blood; D000818:Animals; D001806:Blood Urea Nitrogen; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015735:Mifepristone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D014508:Urea / Q000378:metabolism*
D000596:Amino Acids; D007375:Interleukin-1; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins; D015735:Mifepristone; D014508:Urea