Clearance and tissue distribution of recombinant human interleukin 1β (IL-1β) were investigated by determining the growth-inhibitory activity on tumor cells in rats after i.v. or s.c. administration.
A single 100 µg/kg i.v. bolus was biphasically eliminated with a terminal half-life of 19.0 min in normal rats. Serum IL-1β 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-1β activity was mainiy located in the kidney and was particularly accumulated in the lysosomal fraction. A 14-fold increase in the elimination half-life of IL-1β activity was found in nephrectomized rats, in comparison with shamtreated control rats. Pretreatment with E-64 and leupeptin, both of which are thiol protease inhibitors, had no effect on the plasma levels of IL-1β activity, but a 2-fold increase in plasma level was found in rats pretreated with pepstatin A, a carboxyl protease inhibitor.
Since excreted IL-1β 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.