Involvement of the Kidney in Catabolism of Human Leukocyte Interferon

Abstract

The metabolic fate of human leukocyte interferon (HuIFN-.alpha.) was studied after i.v. 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 (150,000 g) had a high HuIFN-.alpha. content. HuIFN-.alpha. was rapidly inactivated by 2 types of proteinases found in the lysosomal fractions of rat, monkey and human kidneys, with an optimal pH of 3-4. The inactivation was partially inhibited by either pepstatin or leupeptin. Inactivation was totally prevented by a mixture of both inhibitors. Since interferon is scantily excreted in urine, the kidney apparently serves as a main site for its degradation.