The Kidney is the Main Site of Interferon Degradation

Abstract

Male Sprague Dawley rats (300 g) were infused by constant infusion into the jugular vein through 3–5 h with human leukocyte-derived interferon (HuIFN-α 10⁶ units/h, 0.9 ml/h). Blood samples were collected every 20 min through the carotid. A steady-state level of interferon in serum (10⁴ U/ml) was reached after 50 min of infusion, indicating fast removal of most of the infused material. Examination of interferon distribution in various tissues at the termination of the infusion revealed that over 85% of active interferon was found in the kidneys. No interferon was found in urine. Ligation of both kidneys resulted (after 2.5 h of infusion) in a ten-fold increase in interferon in serum and a minor increase in other tissues. No interferon was found in the kidneys. Simultaneous infusion of HuIFN-α, pepstatin and leupeptin (the well-known inhibitors of lysosomal proteinases) for 2.5 h had no effect on interferon concentration in serum and various tissues except in kidneys where a 5-fold increase was found. Mitochondrial–lysosomal fractions contained 55% of the total kidney interferon. Partial inhibition of proteolytic and HuIFN-α degrading activities at that fraction was also observed. These data, together with our previous findings of accumulation of injected interferon in the mitochondrial–lysosomal fraction of rats and monkeys' kidney cells, provide a further evidence for the main role of the kidney in HuIFN-α degradation.