Clearance and tissue distribution of recombinant human interleukin 1 beta in rats

Kudo, S.; Mizuno, K.; Hirai, Y.; Shimizu, T.

Cancer Research 50(18): 5751-5755


ISSN/ISBN: 0008-5472
PMID: 2393849
Document Number: 366607
Clearance and tissue distribution of recombinant human interleukin 1.beta. (IL-01.beta.) were investigated by determining the growth-inhibitory activity on tumor cells in rats after i.v. or s.c. administration. A single 100 .mu.g/kg i.v. bolus was biphasically eliminated with a terminal half-life of 19.0 min in normal rats. Serum IL-1.beta. activity reached a maximum level 1 h after s.c. administration and then declined with a half-life of 1.59 h. The absolute bioavailability was 40.5%. IL-1.beta. activity was mainly located in the kidney and was particularly accumulated in the lysosomal fraction. A 14-fold increase in the elimination half-life of IL-1.beta. activity was found in nephrectomized rats, in comparison with sham-treated control rats. Pretreatment with E-64 and leupeptin, both of which are thiol protease inhibitors, had no effect on the plasma levels of IL-1.beta. activity, but a 2-fold increase in plasma level was found in rats pretreated with pepstatin A, a carboxyl protease inhibitor. Since excreted IL-1.beta. activity was not detected in urine, these results suggest that the kidney is the main site of its metabolic degradation and that carboxyl protease is involved in its metabolic inactivation.

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