Fate of injected interleukin 1 in rats: sequestration and degradation in the kidney.
The tissue distribution and route of clearance of human recombinant interleukin 1 alpha (IL 1 alpha) injected intravenously in rats was studied. The plasma half-life was approximately 2.5 min, and this was increased after nephrectomy, the kidney being the major organ through which the IL 1 alpha was excreted. Two iodinated fragments of IL 1 alpha, of approximately 5 and 9 kDa, were excreted by the kidneys whereas only intact, 17-kDa IL 1 alpha was detected in plasma, suggesting that the protein was being degraded after uptake by the kidney. The results of in vivo experiments in which surface endopeptidase-24.11 was inhibited with phosphoramidon and in vitro experiments in which rat kidney homogenates were incubated with radiolabeled IL 1 alpha suggest that the cytokine was endocytosed and then hydrolysed by lysosomal proteinases.
Poole
S
S
National Institute for Biological Standards and Control, Potters Bar, Herts, UK.
Bird
T A
TA
Selkirk
S
S
Gaines-Das
R E
RE
Choudry
Y
Y
Stephenson
S L
SL
Kenny
A J
AJ
Saklatvaa
J
J
D000818:Animals; D001345:Autoradiography; D006207:Half-Life; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D009392:Nephrectomy; D010446:Peptide Fragments / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000378:metabolism / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution
D007375:Interleukin-1; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D011994:Recombinant Proteins