Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1979 Jul;16(1):56–63. doi: 10.1128/aac.16.1.56

Human Fibroblast Interferon for Clinical Trials: Pharmacokinetics and Tolerability in Experimental Animals and Humans

Alfons Billiau 1, Piet De Somer 1, Victor G Edy 1, Erik De Clercq 1, Hubertine Heremans 1
PMCID: PMC352788  PMID: 475375

Abstract

Human fibroblast interferon (F-interferon) purified by adsorption on controlled-pore glass was given intramuscularly to patients at daily dosages of up to 20 × 106 units. Serum levels of antiviral activity were low or undetectable. In contrast, reasonably high serum titers were found in patients receiving interferon prepared from leukocytes (L-interferon). Similarly, in rabbits lower serum titers were seen with F-interferon than with L-interferon. These results are at variance with those obtained earlier (V. G. Edy, A. Billiau, and P. De Somer, J. Infect. Dis. 133:A18–A21, 1976). Possible explanations for this discrepancy are discussed. The F-interferon evoked febrile reactions, delayed skin reactivity, and transitory lymphopenia in humans. Some patients developed an allergic state of the reaginic type as evidenced by a weal and flare reaction after intradermal challenge. However, these patients did not show allergic symptoms after intramuscular injections. None of the side effects was severe enough to prohibit continuation of the treatment; most of them seemed to be due to contaminants not removed by the purification method. The possibility is considered that some of the side effects, e.g., delayed skin reactivity, are sufficiently specific to justify identification of the active principals.

Full text

PDF
56

Images in this article

60Image
on p.60

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahström L., Dohlwitz A., Strander H., Carlström G., Cantell K. Letter: Interferon in acute leukaemia in children. Lancet. 1974 Feb 2;1(7849):166–167. doi: 10.1016/s0140-6736(74)92458-1. [DOI] [PubMed] [Google Scholar]
  2. Billiau A., Damme J. V., Leuven F. V., Edy V. G., De Ley M., Cassiman J. J., Van de Berghe H., De Somer P. Human fibroblast interferon for clinical trials: production, partial purification, and characterization. Antimicrob Agents Chemother. 1979 Jul;16(1):49–55. doi: 10.1128/aac.16.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bloom B. R. In vitro approaches to the mechanism of cell-mediated immune reactions. Adv Immunol. 1971;13:101–208. doi: 10.1016/s0065-2776(08)60184-4. [DOI] [PubMed] [Google Scholar]
  4. De Somer P., Edy V. G., Billiau A. Interferon-induced skin reactivity in man. Lancet. 1977 Jul 2;2(8027):47–48. doi: 10.1016/s0140-6736(77)90055-1. [DOI] [PubMed] [Google Scholar]
  5. Desmyter J., De Groote J., Desmet V. J., Billiau A., Ray M. B., Bradburne A. F., Edy V. G., De Somer P. Administration of human fibroblast interferon in chronic hepatitis-B infection. Lancet. 1976 Sep 25;2(7987):645–647. doi: 10.1016/s0140-6736(76)92460-0. [DOI] [PubMed] [Google Scholar]
  6. Dvorak H. F., Mihm M. C., Jr, Dvorak A. M. Morphology of delayed-type hypersensitivity reactions in man. J Invest Dermatol. 1976 Sep;67(3):391–401. doi: 10.1111/1523-1747.ep12514713. [DOI] [PubMed] [Google Scholar]
  7. Edy V. G., Billiau A., De Somer P. Comparison of rates of clearance of human fibroblast and leukocyte interferon from the circulatory system of rabbits. J Infect Dis. 1976 Jun;133 (Suppl):A18–A21. doi: 10.1093/infdis/133.supplement_2.a18. [DOI] [PubMed] [Google Scholar]
  8. Edy V. G., Billiau A., De Somer P. Non-appearance of injected fibroblast interferon in circulation. Lancet. 1978 Feb 25;1(8061):451–452. doi: 10.1016/s0140-6736(78)91251-5. [DOI] [PubMed] [Google Scholar]
  9. Edy V. G., Billiau A., de Somer P. Purification of human fibroblast interferon by zinc chelate affinity chromatography. J Biol Chem. 1977 Sep 10;252(17):5934–5935. [PubMed] [Google Scholar]
  10. Edy V. G., Braude I. A., De Clercq E., Billiau A., De Somer P. Purification of interferon by adsorption chromatography on controlled pore glass. J Gen Virol. 1976 Dec;33(3):517–521. doi: 10.1099/0022-1317-33-3-517. [DOI] [PubMed] [Google Scholar]
  11. Elin R. J., Wolff S. M. Biology of endotoxin. Annu Rev Med. 1976;27:127–141. doi: 10.1146/annurev.me.27.020176.001015. [DOI] [PubMed] [Google Scholar]
  12. Emödi G., Just M., Hernandez R., Hirt H. R. Circulating interferon in man after administration of exogenous human leukocyte interferon. J Natl Cancer Inst. 1975 May;54(5):1045–1049. [PubMed] [Google Scholar]
  13. Greenberg H. B., Pollard R. B., Lutwick L. I., Gregory P. B., Robinson W. S., Merigan T. C. Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis. N Engl J Med. 1976 Sep 2;295(10):517–522. doi: 10.1056/NEJM197609022951001. [DOI] [PubMed] [Google Scholar]
  14. Habif D. V., Lipton R., Cantell K. Interferon crosses blood-cerebrospinal fluid barrier in monkeys. Proc Soc Exp Biol Med. 1975 May;149(1):287–289. doi: 10.3181/00379727-149-38790. [DOI] [PubMed] [Google Scholar]
  15. Jordan G. W., Fried R. P., Merigan T. C. Administration of human leukocyte interferon in herpes zoster. I. Safety, circulating, antiviral activity, and host responses to infection. J Infect Dis. 1974 Jul;130(1):56–62. doi: 10.1093/infdis/130.1.56. [DOI] [PubMed] [Google Scholar]
  16. Kingham J. G., Ganguly N. K., Shaari Z. D., Mendelson R., McGuire M. J., Holgate S. J., Cartwright T., Scott G. M., Richards B. M., Wright R. Treatment of HBsAg-positive chronic active hepatitis with human fibroblast interferon. Gut. 1978 Feb;19(2):91–94. doi: 10.1136/gut.19.2.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Merigan T. C., Rand K. H., Pollard R. B., Abdallah P. S., Jordan G. W., Fried R. P. Human leukocyte interferon for the treatment of herpes zoster in patients with cancer. N Engl J Med. 1978 May 4;298(18):981–987. doi: 10.1056/NEJM197805042981801. [DOI] [PubMed] [Google Scholar]
  18. Scott G. M., Butler J. K., Cartwright T., Richards B. M., Kingham J. G., Wright R., Tyrrell D. A. Interferon skin reactivity and pyrexial reactions. Lancet. 1977 Aug 20;2(8034):402–403. doi: 10.1016/s0140-6736(77)90329-4. [DOI] [PubMed] [Google Scholar]
  19. Strander H., Cantell K., Carlström G., Jakobsson P. A. Clinical and laboratory investigations on man: systemic administration of potent interferon to man. J Natl Cancer Inst. 1973 Sep;51(3):733–742. doi: 10.1093/jnci/51.3.733. [DOI] [PubMed] [Google Scholar]
  20. Weimar W., Heijtink R. A., Schalm S. W., van Blankenstein M., Schellekens H., Masurel N., Edy V. G., Billiau A., De Somer P. Fibroblast interferon in HBsAg-positive chronic active hepatitis. Lancet. 1977 Dec 17;2(8051):1282–1282. doi: 10.1016/s0140-6736(77)92682-4. [DOI] [PubMed] [Google Scholar]
  21. Weimar W., Schellekens H., Lameijer L. D., Masurel N., Edy V. G., Billiau A., De Somer P. Double-blind study of interferon administration in renal transplant recipients. Eur J Clin Invest. 1978 Aug;8(4):255–258. doi: 10.1111/j.1365-2362.1978.tb00861.x. [DOI] [PubMed] [Google Scholar]
  22. Wolff S. M. Biological effects of bacterial endotoxins in man. J Infect Dis. 1973 Jul;128(Suppl):259–264. doi: 10.1093/infdis/128.supplement_1.s259. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES