Interferons biological effects

Interferon -biologic agent -flu-like symptoms-malaise, myalgias, fatigue, fever -nausea and vomiting—mild -anorexia -bone marrow suppression -mucocutaneous effects (stomatitis, mucositis) -cardiovascular effects (arrhythmias, hypotension) -mental status changes (confusion, lethargy, psychosis) -renal impairment (proteinuria) -elevation in transaminase levels... 

Interferons were the first family of cytokines to be discovered. In 1957, researchers observed that susceptible animal cells, if they were exposed to a colonizing virus, immediately became resistant to attack by other viruses. This resistance was induced by a substance secreted by virally infected cells which was named interferon. Subsequently, it has been shown that most species actually produce a whole range of interferons. Humans produce at least three distinct classes, IFN-a, IFN-P and IFN-y (Table 8.4). These interferons are produced by a variety of different cell types and exhibit a wide range of biological effects, including ... 

Interferons induce a wide range of biological effects. Generally, type I interferons induce similar effects, which are distinct from the effects induced by IFN-y. The most pronounced effect of type I interferons relates to their antiviral activity, as well as their anti-proliferative effect on various cell types, including certain tumour cell types. Anti-tumour effects are likely due not only to a direct anti-proliferative effect on the tumour cells themselves, but also due to the ability of type I interferons to increase NK and T-cytotoxic cell activity. These cells can recognize and destroy cancer cells. 

Gutterman, J.U., Fine, S., Quesada, J., Homing, S.J., Levine, J.F., Alexanian, R., Bernhardt, L., Kramer, M., Speigal, H., Colburn, W., Trown, R, Merigan, T. and Dziewanawska, Z. (1982). Recombinant leukocyte A interferon Pharmacokinetics, single-dose tolerance, and biological effects in cancer patients. Ann. Intern. Med. 96 549-556. 

Many cytokines exhibit redundancy, i.e. two or more cytokines can induce a similar biological effect. Examples include TNF-a and -P, both of which bind to the same receptor and induce very similar if not identical biological responses. This is also true of the interferon-a family of proteins and interferon-/ , all of which bind the same receptor. 

Gutterman, J.U., S. Pine, J. Quesada, S.J. Horning, IP. Levine, R. Alexanian, L. Bernhardt, M. Kramer, H. Spiegel, W. Colburn, P. Trown, T. Merigan, and Z. Dziewanowski, Recombinant leukocyte A interferon pharmacokinetics, single-dose tolerance, and biologic effects in cancer patients. Ann Intern Med, 1982. 96(5) 549-56. 

These studies demonstrating a protective effect of sialic acid residues on serum glycoproteins provide an explanation for earlier, conflicting observations about the biological effect of, for example, desialylated erythropoietin, which stimulates erythropoiesis only after direct application to bone-marrow cell-cultures, and not after injection into the blood stream.469 In the latter experiment, only the native, sialylated hormone was active. Rapid clearance and inactivation of follicle-stimulating hormone,470 or interferon,471 after treatment with sialidase may be explained by uptake into liver cells. 

Interferon-stimulated genes modulate many biological effects including inhibition of viral replication in infected cells, inhibition of cellular proliferation and immunomodulation... 

Interferon gamma binds to different cell surface receptors than alpha and beta Specific effect of interferon gamma include enhancement of oxidative metabolism of macrophages, antibody-dependent cellular cytotoxicity, activation of natural killer cells, and expression of Fc and major histocompatibility antigens While all alpha interferon have similar biological effects, not all activities shared by each and in many cases the extent of activity various substantially for each interferon subtype... 

Interferon alfa is used as purified natural leukocyte or lymphoblastoid human interferon, or as a recombinant DNA preparation. Work to assign the most frequently observed amino acids at each position has led to a so-called consensus interferon alfa (1). Relatively low doses (3-10 MU three times a week) are now being used in most indications, except in AIDS-related Kaposi s sarcoma (up to 30 MU/day). Although the half-life is only 4-5 hours, its biological effects persist for 2-3 days. 

Schiller JH, Witt PL, Storer B, Alberti D, Tombes MB, Arzoomanian R, Brown RR, Proctor RA, Voss SD, Spriggs DR, et al. Clinical and biologic effects of combination therapy with gamma-interferon and tumor necrosis factor. Cancer 1992 69(2) 562-71. 

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