A Tale of Two Interferon Bioassays: How Frustration with Discrepant Results from Slightly Dissimilar Methods Can Engender Discovery

  • Alfons BilliauEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 820)


This introductory article describes an episode that took place in the mid-1980s when the first wave of cytokine discoveries took place. During studies aimed at complete purification of human interferon-γ from crude mitogen-stimulated lymphokine preparations, the use of two different antiviral bioassays for the cytokine yielded disparate results. Analysis revealed the presence of a “contaminant” IFN-like cytokine that was detectable with only one of the two assays. Superficially, the contaminant resembled IFN-β. However, further analysis showed that it was not an IFN at all but an IFN-inducing cytokine identifiable as interleukin-1.

Key words

Bioassay Interferon Interleukin Antiviral activity 


  1. 1.
    Billiau, A., Opdenakker, G., Van Damme, J., De Ley, M., Volckaert, G., Van Beeumen, J. (1985) Interleukin-1: amino acid sequencing reveals microheterogeneity and relationship with an interferon-inducing monokine. Immunol. Today 6: 235236.CrossRefGoogle Scholar
  2. 2.
    Billiau, A. (1987) The interferon-interleukin 1 connection. In Interferon, Academic Press Inc., London, Vol. 9 pp.91–111.Google Scholar
  3. 3.
    De Ley, M., Van Damme, J., Claeys, H., Weening, H., Heine, J.W., Billiau, A., Vermylen, C., De Somer, P. (1980) Interferon induced in human leukocytes by mitogens: production, partial purification and characterization. Eur. J. Immunol. 10: 877–883.PubMedCrossRefGoogle Scholar
  4. 4.
    Van Damme, J., De Ley, M., Claeys, H., Billiau, A., Vermylen, C., De Somer, P. (1981) Interferon induced in human leukocytes by concanavalin A: isolation and characterization of gamma and β-type components. Eur. J. Immunol. 11: 937–942.PubMedCrossRefGoogle Scholar
  5. 5.
    Van Damme, J., Billiau, A., De Ley, M., De Somer, P. (1983) An interferon-β-like or interferon-inducing protein released by mitogen-stimulated human leukocytes. J. Gen. Virol. 64: 18191822.PubMedCrossRefGoogle Scholar
  6. 6.
    Van Damme, J., Opdenakker, G., Billiau, A., De Somer, P., De Wit, L., Poupart, P., Content, J. (1985) Stimulation of fibroblast interferon production by a 22 K protein from human leukocytes. J. Gen. Virol. 66: 693700.PubMedCrossRefGoogle Scholar
  7. 7.
    Fujita, T., Reis, L.F., Watanabe, N., Kimura, Y., Taniguchi, T., Vilcek, J. (1989) Induction of the transcription factor IRF-1 and interferon-beta mRNAs by cytokines and activators of second-messenger pathways. Proc. Natl. Acad. Sci. USA 86: 99369940.PubMedCrossRefGoogle Scholar
  8. 8.
    Fibbe, W.E., Van Damme, J., Billiau, A., Voogt, P.J., Duinkerken, N., Kluck, P.M.C., Falkenburg, J.H.F. (1986) Interleukin-1 (22-K factor) induces release of granulocyte-macrophage colony-stimulating activity from human mononuclear phagocytes. Blood 68: 1316–1321.PubMedGoogle Scholar
  9. 9.
    Auron, P.E., Webb, A.C., Rosenwasser, L.J., Mucci, S.F., Rich, A., Wolff, S.M., Dinarello, C.A. (1984) Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc. Natl. Acad. Sci. USA 81: 79077911.PubMedCrossRefGoogle Scholar
  10. 10.
    Van Damme, J., De Ley, M., Opdenakker, G., Billiau, A., De Somer, P., Van Beeumen, J. (1985) Homogeneous interferon-inducing 22 K factor is related to endogenous pyrogen and interleukin-1. Nature 314: 266–268.PubMedCrossRefGoogle Scholar
  11. 11.
    Auron, P.E., Rosenwasser, L.J., Matsushima, K., Copeland, T., Dinarello, C.A., Oppenheim, J.J., Webb, A.C. (1985) Human and murine interleukin 1 possess sequence and structural similarities. J. Mol. Cell. Immunol. 2: 169177.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Rega Institute for Medical ResearchUniversity of Leuven (Katholieke Universiteit Leuven)LeuvenBelgium

Personalised recommendations