Interpreting interest in interferon-α

Systemic lupus erythematosus (SLE) is a chronic auto-immune disease that affects approximately 0.1% of the population, with most afflicted individuals being young women. SLE is characterized by inflammatory destruction of skin, blood elements, joints, kidneys, serosa, central nervous system, and other tissues [1]. Despite intensive efforts by many investigators, the cellular and molecular mechanisms governing inflammation in connective tissue diseases such as SLE remain uncertain, although cytokines are believed to play an important role. The group of cytokines known as interferons was first characterized in 1957. Interferons were named for their ability to 'interfere' with viral replication, conferring resistance to infection transferred from virally infected chick cells into uninfected cells [2]. The therapeutic potential of interferon in viral infection was first demonstrated through its ability to inhibit respiratory virus infection [3]. Interfer-ons have since been proven clinically effective antiviral and antineoplastic therapeutic agents for a variety of disorders (for review [4]). There are two groups of interferons: type I interferons (IFN-α, IFN-β, IFN-ω) and type II interferon (IFN-γ). Human IFN-α was cloned in 1980, and was found to represent a mixture of several closely related proteins expressed from distinct genes [5]. A second type of interferon, IFN-β, is produced mainly by fibroblasts, is a single protein species, and was cloned around the same time [6]. A third species of human type I interferon is known as IFN-ω [7]. IFN-γ is produced by activated T cells and has been found to be a single protein in all animal species [8]. Induction of inter-feron synthesis at high levels is triggered by viruses, and is also induced by a variety of nonviral agents such as bacteria and synthetic polymers [9,10]. The production of IFN-α and IFN-β by virally infected cells induces resistance to viral replication, enhances MHC class I expression, increases antigen presentation, and activates natural killer cells to kill virus-infected cells [11]. Thus, type I interferons are active in both innate and adaptive immunity. The actions of IFN-γ include macrophage activation, increased expression of MHC and antigen processing components, immunoglobulin class switching, and suppression of T-helper-2 responses [11]. Many historical studies have indicated a role for the type I interferon system in both human and murine SLE. Although controversial, some studies have shown that serum derived from lupus patients contains elevated levels of IFN-α [12,13]. The levels of IFN-α in serum correlate with disease severity, as measured by the number of organs …