Fate and biological action of human recombinant interleukin 1 beta in the rat in vivo.
The plasma half life of recombinant human interleukin 1 beta (rhIL 1 beta) was determined in rats by measuring the disappearance of the radioactivity of 125I-labeled rhIL 1 beta from the circulation. The plasma clearance showed a biphasic behavior: an initial fast disappearance (half life of about 3 min) was followed by a second slower one (half life of about 4 h). Twenty minutes after a single-dose injection of 125I-labeled rhIL 1 beta most of the radioactivity was concentrated in kidneys, liver and intestine. rhIL 1 beta induced the synthesis of alpha 1-acid glycoprotein (AGP), alpha 1-cysteine proteinase inhibitor (CPI) and beta-fibrinogen mRNA in liver. Half maximal stimulation was elicited by approximately 3000 U of rhIL 1 beta per animal. The mRNA changes for AGP and CPI were followed by corresponding protein increases in serum. Twenty hours after rhIL 1 beta injection, serum AGP rose from 0.7 to 2.5 mg/ml. CPI increased from 0.3 to 1.9 mg/ml 25 h after administration of rhIL 1 beta. Within 20 h after rhIL 1 beta injection, albumin serum concentration showed a strong decrease, preceded by a reduction in hepatic albumin mRNA levels. Neither changes in albumin synthesis nor degradation can explain this decrease suggesting that other mechanisms such as increased transvascular permeability are involved.
Klapproth
J
J
Institut für Biochemie der RWTH Aachen, FRG.
Castell
J
J
Geiger
T
T
Andus
T
T
Heinrich
P C
PC
D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D000418:Albumins / Q000096:biosynthesis; D000818:Animals; D015152:Blotting, Northern; D015853:Cysteine Proteinase Inhibitors; D005340:Fibrinogen / Q000096:biosynthesis; D007375:Interleukin-1 / Q000493:pharmacokinetics / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D009961:Orosomucoid / Q000096:biosynthesis; D011480:Protease Inhibitors / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution
D000209:Acute-Phase Proteins; D000418:Albumins; D015853:Cysteine Proteinase Inhibitors; D007375:Interleukin-1; D009961:Orosomucoid; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D005340:Fibrinogen