Celebrating Cytokine and Interferon Anniversaries

We are excited to recognize two historic milestones that resonate deeply with the International Cytokine and Interferon Society: the 50th anniversary of the term “cytokine” and the 70th anniversary of the introduction of “Interferons.”

Contributed by Valeriya Smaliy and Susan Carpenter, Ph.D., University of California at Santa Cruz

It was in 1974 that Stanley Cohen first introduced the perdurable term “cytokine.” This marked a significant shift in immunological thinking as at that time the prevailing view was that the immune system operated in isolation from other bodily systems. Accordingly, immune molecular mediators were considered to be produced by lymphocytes, and Dumonde et al. had coined the word “lymphokine” [1], while protein mediators of monocytes/macrophages were called “monokines” [2]. But additional works on Macrophage migration inhibitory factor (MIF), discovered in 1996 [3] and Lymphocyte-activating Factor (now IL-1), reported in 1972 [4] revealed that non-lymphocytic cell types could produce such effectors. Cohen et al. [5] demonstrated this, using virus-infected African green monkey kidney cells, observing MIF-like activities comparable to those derived from lymphocytes. This result led him to speculate that “lymphokines produced by the immune system were merely a subset of a more general family of hormone-like mediators produced by many different kinds of cells” [6]. In Jean-Marc Cavaillon’s interview made for the 30th anniversary of the word [7], Stanley Cohen recognized that the popularity of the word has exceeded his expectations: “Actually, I did little to ‘‘propose’’ the word, other than to use it in talks at various meetings, including the Lymphokine Workshops. Certainly there was no attempt to ‘‘market’’ the word itself, as I thought the concept was more important than the label.”

In 1957, researchers Isaacs and Lindenmann observed that chicken egg chorioallantoic membranes incubated with inactivated influenza virus exhibited a reduced ability of live virus to agglutinate red blood cells. This “interfering substance” was aptly named “interferon” [8]. However, the first report of interferon came three years earlier, in 1954, by Nagano and Kojima. Using an in vivo system, they injected inactivated vaccinia into rabbits, shortly followed by injection of live virus, and found inhibited viral replication. This ‘inhibitory factor’ was published in a French journal [9], as Nagano had spent two years at Institut Pasteur (in Paris), working with Georges Stefanopoulo on yellow fever virus, and developed a great love for French culture. The discoveries and classifications of cytokines and interferons have revolutionized our understanding of the immune system and indeed our ability to treat many diseases. Please join us in celebrating these important milestones without which our society would not exist!

1. Dumonde DC, Wolstencroft RA, Panayi GS, Matthew M, Morley J, Howson WT. “Lymphokines”: non-antibody mediators of cellular immunity generated by lymphocyte activation. Nature. 1969 Oct 4;224(5214):38-42. doi: 10.1038/224038a0.
2. Selinger MJ, McAdam KP, Kaplan MM, Sipe JD, Vogel SN, Rosenstreich DL. Monokine-induced synthesis of serum amyloid A protein by hepatocytes. Nature. 1980 Jun 12;285(5765):498-500.
3. Bloom BR, Bennett B. Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science. 1966 Jul 1;153(3731):80-2. doi: 10.1126/science.153.3731.80.
4. Gery I, Gershon RK, Waksman BH. Potentiation of the T-lymphocyte response to mitogens. I. The responding cell. J Exp Med. 1972 Jul 1;136(1):128-42. doi: 10.1084/jem.136.1.128.
5. Bigazzi PE, Yoshida T, Ward PA, Cohen S. Production of lymphokine-like factors (cytokines) by simian virus 40-infected and simian virus 40-transformed cells. Am J Pathol. 1975 Jul;80(1):69-78.
6. Cohen S, Bigazzi PE, Yoshida T. Commentary. Similarities of T cell function in cell-mediated immunity and antibody production. Cell Immunol. 1974 Apr;12(1):150-9. doi: 10.1016/0008-8749(74)90066-5.
7. Cohen S. Cytokine: more than a new word, a new concept proposed by Stanley Cohen thirty years ago. Cytokine. 2004 Dec 21;28(6):242-7.
8. Isaacs A, & Lindenmann J. Virus interference. I. The interferon. Proc. R. Soc. London B Biol. Sci.; 147: 258
9. Nagano, Y., Kojima, Y. [Immunizing property of vaccinia virus inactivated by ultraviolets rays.] C R Séances Soc Biol Fil. 1954, 148, 1700-1702