Biological and Clinical Properties of the Type 1 Interferons 1型干扰素的生物学和临床特性.pdfVIP

Chapter 21 / Properties of the Type 1 Interferons 365 21 Biological and Clinical Properties of the Type 1 Interferons Douglas W. Leaman, Shaun Rosebeck, and Ernest C. Borden SUMMARY Interferons (IFNs) are class 2 cytokines that carry out important physiological func- tions in higher vertebrates, particularly in the regulation of host adaptive and innate immune responses. The complex type 1 IFN family, which includes IFN-α and IFN-β, will be the focus of this chapter. Virus and other innate immune stimuli induce expres- sion of type 1 IFNs, which then act on responsive cells to establish an antiviral state. Type 1 IFN effects are mediated by the protein products of IFN-responsive genes, the identities and functions of which are only now starting to emerge fully. In a clinical setting, type 1 IFNs, IFN-α in particular, have shown effectiveness against a variety of malignancies. Current efforts aimed at improving pharmacokinetic and pharmacodyna- mic profiles of IFNs, identifying subtypes with novel biological activities and/or estab- lishment of combined treatment modalities involving type 1 IFNs should lead to future improvements in therapeutic effectiveness. Key Words: Interferon subtypes; interferon signaling; interferon-stimulated genes; melanoma; myeloma. 1. INTRODUCTION: INTERFERONS Interferons (IFNs) (1) are class 2 cytokines that carry out important physiological functions in higher vertebrates, particularly in the regulation of host adaptive and innate immune responses (2,3). Known IFNs are currently subclassified as either type 1 or type 2 based on common biochemical features including receptor crossreactivities and/or amino acid sequence similarities, although recently discovered “IFN-like” molecules may soon lead to expansion