Fate and biological action of human recombinant interleukin 1β in the rat in vivo

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Abstract
The plasma half life of recombinant human interleukin 1β (rhIL 1β) was determined in rats by measuring the disappearance of the radioactivity of 125I‐labeled rhIL 1β 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 1β most of the radioactivity was concentrated in kidneys, liver and intestine.rhIL 1β induced the synthesis of α1‐acid glycoprotein (AGP), α1‐cysteine proteinase inhibitor (CPI) and β‐fibrinogen mRNA in liver. Half maximal stimulation was elicited by approximately 3000 U of rhIL 1β per animal. The mRNA changes for AGP and CPI were followed by corresponding protein increases in serum. Twenty hours after rhIL 1β 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 1β. Within 20 h after rhIL 1β 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.