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CA Jacobs, DH Lynch, ER Roux, R Miller, B Davis, MB Widmer, J Wignall, T VandenBos, LS Park and MP Beckmann
Immunex Corporation, Seattle, WA 98101.
The interleukin-4 receptor (IL-4R) is expressed as a 140-Kd membrane
glycoprotein that binds IL-4 with high affinity. Recently, cDNA clones for
the murine IL-4R have been isolated. One clone encodes an integral membrane
protein, while another encodes a protein in which translation is terminated
before the transmembrane region, thus producing a soluble form of the IL-4R
(sIL-4R). HeLa cell clones overexpressing sIL-4R were isolated using a
novel filter-overlay and 125I-IL-4 ligand binding technique. Quantitative
analysis demonstrated that the kinetics and affinity of IL-4 binding to the
recombinant sIL-4R were similar to the native membrane-bound IL-4R. As low
doses of sIL-4R specifically inhibited IL-4-induced proliferative responses
in vitro, sIL-4R biodistribution and elimination parameters were evaluated
to assess the pharmacokinetic potential of sIL-4R as a therapeutic agent.
Pharmacokinetic studies demonstrated that radiolabeled sIL-4R had a
distribution half-life of 9 minutes and an elimination half-life of 2.3
hours following intravenous (IV) administration. When administered by
intraperitoneal or subcutaneous (SC) injection, the elimination half- lives
were prolonged to 4.2 hours and 6.2 hours, respectively. Although the
initial blood level of sIL-4R was reduced if administered by SC injection,
the bioavailability was comparable with IV administration. The main sites
of sIL-4R elimination were the liver and kidney.
This article has been cited by other articles:
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| Copyright © 1991 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
