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J Gen Virol 59 (1982), 39-45; DOI 10.1099/0022-1317-59-1-39
© 1982 Society for General Microbiology

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Involvement of the Kidney in Catabolism of Human Leukocyte Interferon

Tamar Bino1, Habib Edery1, Arieh Gertler2 and Hagai Rosenberg1

1 Israel Institute for Biological Research, Ness Ziona
and 2 The Hebrew University, Faculty of Agriculture, Rehovot, Israel

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 (15000 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.

Keywords: human leukocyte IFN, pharmacokinetics, kidney

Received 30 June 1981; accepted 30 September 1981.


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