1887

Abstract

SUMMARY

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

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1985-04-01
2024-11-09
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References

  1. Anderson P., Yip Y. K., Vilcek J. 1983; Fluman interferon-y is internalized and degraded by cultured fibroblasts. Journal of Biological Chemistry 258:6497–6502
    [Google Scholar]
  2. Bocci V. 1981; Pharmacokinetic studies of interferons. Pharmacology and Therapeutics 13:421–440
    [Google Scholar]
  3. Bocci V. 1982; Catabolism of interferons. Survey of Immunologic Research 1:137–143
    [Google Scholar]
  4. Bocci V. 1983a; What is the role of carbohydrates in interferons?. Trends in Biochemical Sciences 8:431–434
    [Google Scholar]
  5. Bocci V. 1983b; Potential advantages of intralymphatic administration of interferon and biological response modifiers. In Proceedings of the International Symposium on Interferons October 1983, Kyoto, Japan, pp 38–44 Edited by Kishida T. Osaka: Japan Convention Services;
    [Google Scholar]
  6. Bocci V. 1985; The physiological interferon response. Immunology Today 6:7–9
    [Google Scholar]
  7. Bocci V., Viti A. 1966; Plasma and blood volumes estimated by the serum 131I-proteins method in normal rabbits of varying body weight. Quarterly Journal of Experimental Physiology 51:27–32
    [Google Scholar]
  8. Bocci V., Pacini A., Muscettola M., Paulesu L., Pessina G. P. 1981; Renal metabolism of rabbit serum interferon. Journal of General Virology 55:297–304
    [Google Scholar]
  9. Bocci V., Pacini A., Bandinelli L., Pessina G. P., Muscettola M., Paulesu L. 1982a; The role of liver in the catabolism of human α- and β-interferon. Journal of General Virology 60:397–400
    [Google Scholar]
  10. Bocci V., Pacini A., Muscettola M., Pessina G. P., Paulesu L., Bandinelli L. 1982b; The kidney is the main site of interferon catabolism. Journal of Interferon Research 2:309–314
    [Google Scholar]
  11. Bocci V., Maunsbach A. B., Mogensen E. K. 1984; Autoradiographic demonstration of human 125l-interferon alpha in lysosomes of rabbit proximal tubule cells. Journal of Submicroscopic Cytology 16:753–757
    [Google Scholar]
  12. Bocci V., Pessina G. P., Pacini A., Paulesu L., Muscettola M., Naldini A., Lunghetti G. 1985; Pharmacokinetics of human lymphoblastoid interferon in rabbits. General Pharmacology (in press)
    [Google Scholar]
  13. Brandani-Pacini A., Bocci V. 1983; An analysis of the optimal conditions for perfusing an isolated rabbit kidney with homologous blood. Renal Physiology 6:72–79
    [Google Scholar]
  14. Cantell K., Hirvonen S., Pyhala L., De Reus A., Schellekens H. 1983; Circulating interferon in rabbits and monkeys after administration of human gamma interferon by different routes. Journal of General Virology 64:1823–1826
    [Google Scholar]
  15. Gutterman J. U., Rosenblum M. G., Rios A., Fritsche H. A., Quesada J. R. 1984; Pharmacokinetic study of partially pure y-interferon in cancer patients. Cancer Research 44:4164–4171
    [Google Scholar]
  16. Langford M. P., Weigent D. A., Stanton G. J., Baron S. 1981; Virus plaque-reduction assay for interferon: microplaque and regular macroplaque reduction assays. In Methods in Enzymology, Interferons Part A, pp 339–346 Edited by Pestka S. New York: Academic Press;
    [Google Scholar]
  17. Osther K., Georgiades J., Hirai N., Pardue A., Hilario R., Aleman C., Khan A., Shah S., Hill J. M., Hill N. O. 1983; Phase I and phase II trials with human gamma interferon. In The Biology of the Interferon System pp 527–533 Edited by De Maeyer E., Schellekens H. Amsterdam: Elsevier Science Publishers;
    [Google Scholar]
  18. Pestka S., Kelder B., Familletti P. C., Moschera J. A., Crowl R., Kempner E. S. 1983; Molecular weight of the functional unit of human leukocyte, fibroblast and immune interferons. Journal of Biological Chemistry 258:9706–9709
    [Google Scholar]
  19. Revel M., Mory Y., Rubinstein M., Segev D., Fellous M., Hahn T., Wallach D. 1984; Production of human interferon-y by DNA-transformed rodent cells and immunoregulation by human interferons: enhancement of histocompatibility antigens and regulation of cell killing. In International Serono Symposium on Immunopharmacology March 1984 Taormina: (in press)
    [Google Scholar]
  20. Yip Y. K., Pang R. H. L., Urban C., Vilcek J. 1981; Partial purification and characterization of human y (immune) interferon. Proceedings of the National Academy of Sciences, U,. S,. A 78:1601–1605
    [Google Scholar]
  21. Yip Y. K., Barrowclough B. S., Urban C., Vilcek J. 1982; Molecular weight of human y-interferon is similar to that of other human interferons. Science 215:411–413
    [Google Scholar]
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