Pharmacokinetics, Tissue Distribution, and Cell Localization of [35S]Methionine-labeled Recombinant Human and Murine α Interferons in Mice

Terrance G. Johns, Julie A. Kerry, Barry A.J. Veitch, Ian R. Mackay, Peter J. Tutton, Martin J. Tymms, Brian F. Cheetham, Paul J. Hertzog, Anthony W. Linnane

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Abstract

The pharmacokinetics, tissue distribution, cell localization, and penetration into tumor xenografts of recombinant [35S]methionine-labeled human a interferon (MuIFN-α) and murine a interferon (MuIFNα) were examined in mice. Both interferons (IFNs) were removed from the blood in a rapid biphasic manner; HuIFNα was cleared faster than MuIFN-α. Tissues were analyzed for radioactivity and over 90% of the IFNs was accounted for. The IFNs were detected predominantly in liver, kidney, gastrointestinal tract, pancreas, spleen, and lung. The levels of MuIFN-α compared with HuIFNα were greater in the liver, spleen, and lung and less in the kidney, pancreas, and gastrointestinal tract. Heart, brain, testes, thymus, lymph nodes, fat, skin, and skeletal muscle contained much lower but measurable levels of both IFNs. There was penetration of HuIFNα into tumor xenografts. The pharmacokinetics of IFNα were independent of the strain of mouse, BALB/c or CBA, immune deprivation, or the presence of a tumor xenograft. Autoradiography of tissue sections from mice given injections of HuIFNα or MuIFNα indicated focal radioactivity in proximal convoluted tubules in the kidney and diffuse radioactivity in the liver, gastrointestinal tract, and pancreas. MuIFNα, but not HuIFNα, showed intense localization in cells in hepatic sinusoids, marginal zones in the spleen, and pulmonary alveolar walls, suggesting uptake by cells of the monocyte/macrophage lineage in these sites. The study shows the utility of biosynthetic labeling for pharmacokinetic studies of cytokines, clear differences in tissue distribution of IFNα according to its species of origin, and targeting of homologous IFNα to cells of the monocytic lineage.

Original languageEnglish
Pages (from-to)4718-4723
Number of pages6
JournalCancer Research
Volume50
Issue number15
Publication statusPublished - 1 Aug 1990

Cite this

Johns, T. G., Kerry, J. A., Veitch, B. A. J., Mackay, I. R., Tutton, P. J., Tymms, M. J., Cheetham, B. F., Hertzog, P. J., & Linnane, A. W. (1990). Pharmacokinetics, Tissue Distribution, and Cell Localization of [35S]Methionine-labeled Recombinant Human and Murine α Interferons in Mice. Cancer Research, 50(15), 4718-4723.