FATE AND BIOLOGICAL ACTION OF HUMAN RECOMBINANT INTERLEUKIN 1-BETA IN THE RAT INVIVO

FATE AND BIOLOGICAL ACTION OF HUMAN RECOMBINANT INTERLEUKIN 1-BETA IN THE RAT INVIVO
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DOI:
10.1002/eji.1830190821
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发表时间:
1989-08-01
影响因子:
5.4
通讯作者:
HEINRICH, PC
HEINRICH, PC
中科院分区:
医学3区
文献类型:
--
作者:
KLAPPROTH, J;CASTELL, J;HEINRICH, PC

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重组人白细胞介素1 β的血浆半衰期(rhIL 1 β)通过测量125 I标记的rhIL 1 β的放射性消失来测定大鼠中的从循环。血浆清除率显示出双相行为:最初的快速消失(半衰期约为3分钟),其次是第二个较慢的(半衰期约为4小时)。单剂量注射125 I标记的rhIL 1 β后20分钟。大部分放射性集中在肾、肝和肠中。rhIL 1 β诱导α 1-酸性糖蛋白(AGP)、α 1-半胱氨酸蛋白酶抑制剂(CPI)和β-肝纤维蛋白原mRNA。通过约3000 U的rhIL 1 β引起半数最大刺激。每只动物。AGP和CPI的mRNA变化伴随着血清中相应蛋白的增加。rhIL 1 β后20小时。注射后,血清AGP从0.7上升到2.5mg/ml。给予rhIL 1 β后25小时,CPI从0.3 mg/ml增加至1.9 mg/ml。rhIL 1 β.注射后,血清白蛋白浓度显示出强烈的降低,之前是肝白蛋白mRNA水平的降低。白蛋白合成和降解的变化都不能解释这种降低,这表明涉及其他机制,如经血管渗透性增加。
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.