Catabolic sites of human interferon-gamma

Recombinant human interferon-gamma (HuIFN-gamma) injected into rabbits disappeared from the circulation more rapidly than natural IFN-gamma. The latter displayed an initial decay curve more rapid than that for natural HuIFN-alpha although 4 h after injection plasma levels were similar. This result suggests that IFN-gamma has pharmacokinetic properties different to those of IFN-alpha which may be explained by considerable and simultaneous hepatic and renal catabolism. Surprisingly, the hepatic uptake of recombinant (unglycosylated) IFN-gamma was more marked than uptake of natural IFN-gamma. Moreover, both IFN-gamma preparations were cleared by the isolated and perfused kidney and once again the recombinant IFN disappeared more rapidly. This result does not conform with the suggestion that IFN-gamma exists as a tetramer which would not be filtered by the glomerulus, but is consistent with the pharmacokinetic behaviour shown in vivo.