Interferon-β exacerbates Th17-mediated inflammatory disease

Abstract

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.

Figure

Autoimmune diseases with a predominately IL-23–Th17 response secrete high levels of IL-17A and IL-17F, which signals to the surrounding tissue to up-regulate granulocyte recruitment and activation factors, such as G-CSF, Gro-α and IL-8. Through a currently unknown mechanism, endogenous expression of IFN-β by plasmacytoid DCs or therapeutic administration of IFN-β, worsens Th17 disease. Conversely, predominantly Th1-mediated diseases have high levels of IFN-γ and have a lymphocytic and macrophage infiltrate. In Th1 disease, IFN-β, in concert with IFN-γ, drives anti-inflammatory responses such as upregulation of IL-27, IL-10 or inhibiting chemokine expression by macrophages.