IFN Beta-1b Research Articles

The role of interferons in the treatment of multiple sclerosis.

IFN beta-1b clearly alters the course of disease in patients with relapsing-remitting MS, although the adverse effects of this agent may discourage some patients from continuing the therapy. Nurses can help patients with MS minimize adverse effects through teaching. A double-blind, placebo-controlled clinical trial in patients with relapsing-progressive MS will be started in 1995. It is hoped that IFN beta-1b will be effective in slowing the accumulation of CNS lesions in those with progressive MS.

Reconstitution of a High Affinity Binding Site for Type I Interferons

The type I interferon (IFN) receptor complex is assumed to be composed of multiple protein subunits. Recently, two proteins have been identified as potential receptor components, both of which share a high degree of structural homology with the immunoglobulin superfamily. One of these proteins, referred to as the human interferon alpha receptor (IFNAR), has been shown to be involved in interferon signal transduction, but it does not bind IFN with high affinity. A second putative receptor protein, named FLP40, has been cloned from human Daudi cells. Transfection of FLP40 into murine NIH 3T3 cells does not result in high affinity IFN binding. In this study, we demonstrate that when expressed in murine L929 cells neither IFNAR nor FLP40 by themselves are capable of binding human IFN-alpha 8. Co-expression of IFNAR and FLP40 results in cells capable of binding IFN-alpha 8 and IFN-alpha 2. Scatchard analysis of binding demonstrated the presence of high (KD 350 pM) and low (KD 4.0 nM) affinity binding sites. Binding of radiolabeled IFN-alpha 8 can be competed with either unlabeled IFN-alpha 8 or a recombinant form of human interferon beta, IFN-beta 1b, but not with IFN-gamma. Ligand binding of IFN-alpha 8 can be inhibited by antibodies directed against IFNAR providing further support for a role for this protein in the formation of a ligand binding site. This is the first demonstration indicating that two previously identified IFN receptor proteins, which individually do not bind type I IFN with high affinity, cooperate in the formation of a type I IFN receptor ligand binding complex.

The effect of interferon‐β on blood—brain barrier disruptions demonstrated by constrast‐enhanced magnetic resonance imaging in relapsing—remitting multiple sclerosis

Magnetic resonance imaging (MRI) has been a valuable tool to understand the pathophysiology and natural history of multiple sclerosis (MS), and increasing attention is focusing on the use of MRI findings as outcome measures in treatment trials in MS. The recently completed trial of interferon-beta-1b (IFN-beta 1b) demonstrated a decrease in accumulation of diseased tissue on T2-weighted images and a reduction in new lesions on T2-weighted images. To examine the effect of IFN-beta 1b on blood-brain barrier (BBB) breakdown, and to provide additional insights into the usefulness of MRI in the evolution of effectiveness of experimental treatments in MS, we used the contrast-enhanced lesion frequency of 7-month baseline MRIs compared with the enhanced lesion frequency for 6-month treatment period MRIs in 14 relapsing-remitting (RR) MS patients. Longer baselines were also available for analysis in a subset of 8 patients, as these patients had been followed by monthly MRI in a natural history study for up to 4 years prior to the current study. A significant reduction in the total or new enhancing lesion frequency was detected in the patients analyzed as a whole, and 13 of 14 of the patients demonstrated a reduction in enhancing lesion frequency on treatment over the 6 months studied. These findings suggest that IFN-beta has a mechanism of action that at least temporarily inhibits the opening of the BBB in RRMS patients. This trial also illustrates the usefulness of a baseline versus treatment trial design to evaluate the effect of drug therapy in MS.