Immunomodulatory activity of interferon-beta

Abstract

Multiple sclerosis (MS) is a complex disorder of the central nervous system that appears to be driven by a shift in immune functioning toward excess inflammation that results in demyelination and axonal loss. Beta interferons were the first class of disease-modifying therapies to be approved for patients with MS after treatment with this type I interferon improved the course of MS on both clinical and radiological measures in clinical trials. The mechanism of action of interferon-beta appears to be driven by influencing the immune system at many levels, including antigen-presenting cells, T cells, and B cells. One effect of these interactions is to shift cytokine networks in favor of an anti-inflammatory effect. The pleiotropic mechanism of action may be a critical factor in determining the efficacy of interferon-beta in MS. This review will focus on select immunological mechanisms that are influenced by this type I cytokine.

Figure 1

T-cell polarization (A) in patients with untreated MS and (B) under the effects of interferon-beta. Effector and regulatory T-cell polarization is driven by cytokines that influence the phenotype of the polarized cell. Patients with MS have an increased number of Th17 cells, which are polarized by IL-6 and TGF-β, leading to increased secretion of pro-inflammatory IL-17., Interferon-beta inhibits Th17 differentiation, leading to a decrease in IL-17 secretion. In addition to this effector cell phenotype, patients with MS also have a dysregulated Treg response by Foxp3+ cells that is unable to suppress Th17 cell activity. Treatment with interferon-beta increases the number of Foxp3+ cells by increasing production of IL-4, IL-5, and IL-13, thereby helping to return the secretion of IL-17 by Th17 cells to a level similar to healthy patients., MS, multiple sclerosis; IL, interleukin; TGF, transforming growth factor.