The Fate of [¹²⁵I] -Labeled Human Leukocyte-Derived Alpha Interferon in the Rat

In order to follow the catabolic fate of interferon in the body, |¹²⁵I]-labeled human alpha interferon was infused into rats. Interferon activity and TCA-precipitable radioactivity in the blood reached a steady state after 60 min of infusion, while TCA-soluble radioactivity continued to increase during the entire infusion period. A massive accumulation of both active interferon and degradation products of interferon were found in the kidney at the end of the infusion. Most of the interferon activity was found in the mitochondrial-lysosomal fraction, while most of the interferon degradation products were found in the supernatant fraction. Ligation of the kidney's blood vessels resulted in a large increase of interferon activity in the blood. Only a small increase was found in other organs, with no increase at all in radioactive degradation products. Our results suggest the kidney to be the main site of interferon catabolism. Low molecular weight degradation products are excreted from the kidney into the blood and are at least partially secreted in the urine and also taken up by other organs.