Interferons: Mechanisms, Biological Activities and Survey of their Use in Human Diseases

Dalia      Obeid; Brigitte      Bauvois

doi:10.2174/157340706778992591

Abstract

Human interferons (IFNs) form a family of cytokines produced by a large number of cells. On the basis of their physicochemical and biological properties, the IFN family can be subdivided into two subtypes: the Type I IFNs (α,β,ω) and the Type II IFN represented by IFN-γ. IFN binding to specific cell surface receptors activates the Jaks kinases which phosphorylate Stats leading to their dimerization, translocation to the nucleus, and activation of their transcription factor activity. In addition, IFNs activate several protein kinases including the MAP kinase family, and downstream transcription factors through Stat-independent pathways. IFNs could induce the expression of more than 300 genes. Through these Stat-dependent and Stat-independent pathways, IFNs exhibit antiviral, antitumor, and immune-enhancing properties. Recombinant DNA technology has allowed IFNs to be produced in sufficient quantity for large scale clinical studies. IFNs are effective in the treatment of viral diseases (hepatitis B and C, VIH, HPV), solid tumors (melanoma, Kaposis sarcoma, renal and hepatocellular carcinomas), hematological disorders (hairy cell leukemia, multiple myeloma, chronic granulomatosis) and in other diseases such as multiple sclerosis and infancy hemangioma. The limitations to their clinical use include side effects such as induced toxicity and development of antibodies in patients. Pegylated IFNs (IFN covalently bound to polyethylene glycol polymers) with little inmunogenicity, longer plasma half-life, greater stability and efficacy, as single agents or in combination with other therapeutic agents, appear to improve IFN clinical efficacy. New options involve IFN gene therapy.

Keywords: Cancer, hepatitis, interferon, leukemia, multiple sclerosis, pegylation, vaccine, virus