Safety, Tolerability, and Immunogenicity of Interferons 英文参考文献.docVIP

Pharmaceuticals 2010, 3, 1162-1186; doi:10.3390/ph3041162 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Safety, Tolerability, and Immunogenicity of Interferons Michael G. Tovey * and Christophe Lallemand Laboratory of Viral Oncology, FRE2937 CNRS, Institut André Lwoff, 7 rue Guy-Moquet, 94801 Villejuif, France * Author to whom correspondence should be addressed; E-Mail: tovey@rs.fr; Tel.: +33 1 49 58 34 23; Fax: +33 1 49 58 34 44. Received: 9 March 2010; in revised form: 3 April 2010 / Accepted: 12 April 2010 / Published: 20 April 2010 Abstract: Interferons (IFNs) are class II cytokines that are key components of the innate immune response to virus infection. Three IFN sub-families, type I, II, and III IFNs have been identified in man, Recombinant analogues of type I IFNs, in particular IFN?2 and IFN?1, have found wide application for the treatment of chronic viral hepatitis and remitting relapsing multiple sclerosis respectively. Type II IFN, or IFN gamma, is used principally for the treatment of chronic granulomatous disease, while the recently discovered type III IFNs, also known as IFN lambda or IL-28/29, are currently being evaluated for the treatment of chronic viral hepatitis. IFNs are in general well tolerated and the most common adverse events observed with IFN? or IFN? therapy are “flu-like” symptoms such as fever, headache, chills, and myalgia. Prolonged treatment is associated with more serious adverse events including leucopenia, thrombocytopenia, increased hepatic transaminases, and neuropsychiatric effects. Type I IFNs bind to high-affinity cell surface receptors, composed of two transmembrane polypeptides IFNAR1 and IFNAR2, resulting in activation of the Janus kinases Jak1 and Tyk2, phosphorylation and activation of the latent cytoplasmic signal transducers and activators of transcription (STAT1) and STAT2, for