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Abstract
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.