The protease inhibitor, Bowman-Birk inhibitor, suppresses experimental autoimmune encephalomyelitis (131.33)

Abstract

Abstract The Bowman-Birk inhibitor (BBI) is a soybean-derived serine protease inhibitor. BBI concentrate (BBIC) is enriched with BBI, but is predominantly made up of other ingredients. In our previous study we found that oral administration of BBIC to Lewis rats with EAE resulted in significant clinical and histological suppression of disease. In the present study we investigated the effect of BBI using mouse EAE models and pure BBI. We found that both I.P. and oral treatment with BBI (typically 1 mg/day BBI) in SJL/PLP139–151, or C57BL/6/MOG35–55 models, significantly improved clinical and histological parameters of EAE (disease onset, severity, weight loss, inflammation and demyelination). This was true for different treatment regimens as regards the day of treatment initiation relative to immunization for EAE induction. In most experiments antigen-specific proliferation of immune cells derived from BBI-treated mice was significantly lower relative to control groups. In the SJL model of optic neuritis BBI significantly reduced the incidence of neuritis, inhibited inflammation and prevented loss of retinal ganglion cells. Using Boyden’s chamber assay we found that BBI inhibited invasiveness of activated splenocytes through the matrigel barrier. These results indicate that BBI is an excellent candidate for oral therapy in multiple sclerosis.