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

Abstract

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.

Interferon-β Treatment for Multiple Sclerosis

“…13,14 Interferon-␤ reduces the migration of inflammatory cells across the blood-brain barrier, seen as a rapid decrease in gadolinium-enhancing lesions. 15 This is likely accomplished by indirectly reducing the quantity of functional endothelial adhesion molecules (ICAM and VCAM) 16 and by downregulating the production of chemokines and matrix metalloproteinases, 14 all of which decrease the ability of T lymphocytes to transmigrate across the blood-brain barrier.…”

Recent progress in the diagnosis and treatment of multiple sclerosis

“…This study did not demonstrate a significant beneficial effect of interferon beta-1b therapy on the progression of disability; however, it was not originally designed to detect such an effect. Interferon beta-1b therapy also significantly reduces the number of gadolinium enhanced MRI lesions in patients with relapsing-remitting MS. 33 Gadolinium enhancement indicates a breakdown of the blood-brain barrier and correlates with a marked perivascular accumulation of inflammatory cells; 34 it precedes other MRI abnormalities and clinical evidence of the new lesion. 35 In general, treatment with interferon beta-1b is well tolerated.…”

Early stage and long term treatment of multiple sclerosis with interferon-β

“…10,11 This effect is most vividly demonstrated by the dramatic reduction in gadolinium-enhancing lesions seen on MRI almost immediately after treatment with IFNβ is begun. 12 Interferons were also recently found to demonstrate a direct stabilizing effect on endothelial cells in vitro limiting the migration of small particles into the CNS. 13 Another potential mechanism involves the adhesion of activated T cells to the endothelial surface.…”