PMID- 2039820
OWN - NLM
STAT- MEDLINE
DCOM- 19910710
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 77
IP  - 11
DP  - 1991 Jun 1
TI  - Characterization and pharmacokinetic parameters of recombinant soluble 
      interleukin-4 receptor.
PG  - 2396-403
AB  - 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.
FAU - Jacobs, C A
AU  - Jacobs CA
AD  - Immunex Corporation, Seattle, WA 98101.
FAU - Lynch, D H
AU  - Lynch DH
FAU - Roux, E R
AU  - Roux ER
FAU - Miller, R
AU  - Miller R
FAU - Davis, B
AU  - Davis B
FAU - Widmer, M B
AU  - Widmer MB
FAU - Wignall, J
AU  - Wignall J
FAU - VandenBos, T
AU  - VandenBos T
FAU - Park, L S
AU  - Park LS
FAU - Beckmann, M P
AU  - Beckmann MP
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Receptors, Interleukin-4)
RN  - 0 (Receptors, Mitogen)
RN  - 0 (Recombinant Proteins)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Electrophoresis, Polyacrylamide Gel
MH  - HeLa Cells/immunology
MH  - Humans
MH  - Interleukin-4/*metabolism
MH  - Kinetics
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Molecular Weight
MH  - Receptors, Interleukin-4
MH  - Receptors, Mitogen/immunology/isolation & purification/*metabolism
MH  - Recombinant Proteins/immunology/isolation & purification/metabolism
MH  - T-Lymphocytes/immunology
MH  - Tissue Distribution
EDAT- 1991/06/01 00:00
MHDA- 1991/06/01 00:01
CRDT- 1991/06/01 00:00
PHST- 1991/06/01 00:00 [pubmed]
PHST- 1991/06/01 00:01 [medline]
PHST- 1991/06/01 00:00 [entrez]
AID - S0006-4971(20)77827-4 [pii]
PST - ppublish
SO  - Blood. 1991 Jun 1;77(11):2396-403.