Interferon-β stabilizes barrier characteristics of the blood–brain barrier in four different species in vitro

Abstract

Background Blood–brain barrier (BBB) breakdown is an early event in the pathogenesis of multiple sclerosis (MS). In a previous study we have found a direct stabilization of barrier characteristics after treatment of bovine brain capillary endothelial cells (BCECs) with human recombinant interferon-β-1a (IFN-β-1a) in an in vitro BBB model. In the present study we examined the effect of human recombinant IFN-β-1a on the barrier properties of BCECs derived from four different species including humans to predict treatment efficacy of IFN-β-1a in MS patients. Methods We used primary bovine and porcine BCECs, as well as human and murine BCEC cell lines. We investigated the influence of human recombinant IFN-β-1a on the paracellular permeability for 3H-inulin and 14C-sucrose across monolayers of bovine, human, and murine BCECs. In addition, the transendothelial electrical resistance (TEER) was determined in in vitro systems applying porcine and murine BCECS. Results We found a stabilizing effect on the barrier characteristics of BCECs after pretreatment with IFN-β-1a in all applied in vitro models: addition of IFN-β-1a resulted in a significant decrease of the paracellular permeability across monolayers of human, bovine, and murine BCECs. Furthermore, the TEER was significantly increased after pretreatment of porcine and murine BCECs with IFN-β-1a. Conclusion Our data suggest that BBB stabilization by IFN-β-1a may contribute to its beneficial effects in the treatment of MS. A human in vitro BBB model might be useful as bioassay for testing the treatment efficacy of drugs in MS.