The renal handling of human interferon-alpha has been evaluated by using an isolated and perfused rabbit kidney. IFN-alpha disappears from plasma with a t1/2 of 81 min and the fractional turnover rate is 0.84%/min. About 47 molecules of IFN-alpha are filtrated with 100 molecules of creatinine but most of the IFN is absorbed by tubular cells. This is the first report showing that human IFN-alpha is filtrated by the kidney, largely absorbed, most probably catabolized within tubular epithelium and excreted in negligible amounts with the urine.

Induction of gamma interferon in human lymphoid cells cultures appears to be dependent upon specific membrane-mediated events and calcium flux. Since blastic response had been observed after enzymic oxidation of membrane-bound galactose residues, we used this system to study the nature of membrane alterations responsible for the activation of interferon induction. The results of these experiments suggest that a membrane oxidation is essential for interferon induction and depletion of calcium abolishes interferon production. In addition, we have shown that interferon induction by concanavalin A, phytohemagglutinin, and staphylococcal enterotoxin A, but not by galactose oxidase is prevented by cleavage of N-acetylneuraminic acid residues. Thus, interferon induction in human lymphoid cell cultures by galactose oxidase, concanavalin A, phytohemagglutinin, staphylococcal enterotoxin A, and NaIO4 appears to reside in terminal oligosaccharides of the cell membrane. How this specific membrane event relates to the derepression of the interferon locus is being actively pursued.

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