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

¹ Department of Neurology, Paracelsus Private Medical University and Salzburger Landesklinken, Christian-Doppler-Klinik, Salzburg, Austria; Department of Neurology, University Hospital of Münster, Münster, Germany
² Research Group for Multiple Sclerosis and Neuroimmunology, Department of Neurology, Justus-Liebig University of Giessen, Giessen, Germany
³ Department of Thoracic and Cardiovascular Surgery, Johann-Wolfgang-Goethe University of Frankfurt, Frankfurt am Main, Germany
⁴ Department of Trauma and Hand Surgery, Heinrich-Heine University of Duesseldorf, Duesseldorf, Germany
⁵ Department of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA
⁶ Department of Neurology, University Hospital of Münster, Münster, Germany
⁷ Theodor Kocher Institute, University of Bern, Bern, Switzerland

^* To whom correspondence should be addressed.

	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--1a (IFN--1a) in an in vitro BBB model. In the present study we examined the effect of human recombinant IFN--1a on the barrier properties of BCECs derived from four different species including humans to predict treatment efficacy of IFN--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--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--1a in all applied in vitro models: addition of IFN--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--1a.

Conclusion

Our data suggest that BBB stabilization by IFN--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.

Key Words: blood–brain barrier, cell culture, endothelial cells, immunology, interferon-, multiple sclerosis

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