Trends in Immunology
Volume 32, Issue 6, June 2011, Pages 272-277
Journal home page for Trends in Immunology

Review
Interferon-β exacerbates Th17-mediated inflammatory disease

https://doi.org/10.1016/j.it.2011.03.008Get rights and content

Interferon (IFN)-β is the treatment most often prescribed for relapsing–remitting multiple sclerosis (RRMS). 30–50% of MS patients, however, do not respond to IFN-β. In some cases, IFN-β exacerbates MS, and it consistently worsens neuromyelitis optica (NMO). To eliminate unnecessary treatment for patients who are non-responsive to IFN-β, and to avoid possible harm, researchers are identifying biomarkers that predict treatment outcome before treatment is initiated. These biomarkers reveal insights into the mechanisms of disease. Recent discoveries on human samples from patients with RRMS, NMO, psoriasis, rheumatoid arthritis, systemic lupus erythematosus and ulcerative colitis, indicate that IFN-β is ineffective and might worsen clinical status in diverse diseases when a Th17 immune response is prominent.

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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