Involvement of the kidney in catabolism of human leukocyte interferon

The metabolic fate of human leukocyte interferon (HuIFN-alpha) was studied after intravenous injection into rats and cynomolgus monkeys. At various intervals the animals were sacrificed and the HuIFN-alpha content determined in serum and various tissues. HuIFN-alpha quickly disappeared from the circulation and was found mainly in the kidneys, in which levels were at least 7- to 10-fold higher than in the liver, spleen, lungs, heart, brain and muscles. No interferon was detected in urine. Subcellular fractionation of kidney revealed that the mitochondrial-lysosomal fraction (15 000 g) had a high HuIFN-alpha content. It was also found that HuIFN-alpha was rapidly inactivated by two types of proteinases found in the lysosomal fractions of rat, monkey and human kidneys, with an optimal pH of 3 to 4. The inactivation was partially inhibited by either pepstatin or leupeptin. Inactivation was totally prevented by a mixture of both inhibitors. Since it is known that interferon is scantily excreted in urine, our findings suggest that the kidney serves as a main site for its degradation.