Trends in Immunology
ReviewInterferon-β exacerbates Th17-mediated inflammatory disease
Section snippets
Relapse-remitting multiple sclerosis (RRMS) and interferon (IFN)-β therapy: unmet need for rational prescriptions
Type I IFNs, which include the various IFN-β and IFN-α molecules, were first discovered in virally infected chick embryo cells [1]. They bestow cells with virus resistance. This pleotropic cytokine family is now known to have antiviral, antitumor and immunoregulatory functions. In autoimmunity and inflammation, type I IFNs possess both pro- and anti-inflammatory functions depending on the context of the particular pathology.
The various forms of recombinant IFN-β are collectively the most
Understanding the mode of action of IFN-β treatment: lessons from EAE
Understanding the mechanism whereby IFN-β is effective in RRMS is formidable. Obtaining well-characterized MS tissue at various stages of disease, both before and during treatment is rare. Such specimens are usually limited to the blood. Given the barrier of obtaining such samples from RRMS patients, various models of EAE in rodents, primarily mice, have been used to dissect mechanisms of action for therapy with IFN-β 8, 9, 10, 19, 20. However, identifying the mechanism whereby IFN-β attenuates
Understanding IFN-β response in RRMS
The clinical trials that have led to the approval of IFN-β in RRMS patients have indicated that some patients do not respond to treatment. One theory that explains the lack of response to treatment is poor bioavailability of IFN-β in these patients. One well known cause for the decreased bioavailability is the development of neutralizing antibodies to IFN-β. Several studies have identified that, in some non-responders, repeated injections of recombinant IFN-β elicits an antibody response
Role of IFN-β in autoimmune diseases other than RRMS
RRMS is the one of the few known autoimmune diseases in which the anti-inflammatory effects of IFN-β can be harnessed as a therapy. IFN-β is notably ineffective in RA, for example [34]. In fact, it is striking that the main treatment for RA, tumor necrosis factor (TNF) blockade, has been shown to worsen MS symptoms, and this drug carries an FDA black box warning against this contraindication http://www.fda.gov/OHRMS/DOCKETS/ac/01/briefing/3779b2_01_cber_safety%20_revision2.pdf. However, trials
Concluding remarks
RRMS is a complex disease that has an unpredictable clinical course, with variable pathological patterns. RRMS might not be a single disease, but rather a collection of different syndromes that cause inflammatory demyelination. This heterogeneity is illuminated by the variability in responses to IFN-β. This variability poses a challenge to clinicians and researchers to develop ways to identify responsiveness early after treatment begins, or better yet, before treatment is initiated.
In this
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