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

Department of Neurology, Paracelsus Private Medical University and Salzburger Landesklinken, Christian-Doppler-Klinik, Salzburg, Austria; Department of Neurology, University Hospital of Münster, Münster, Germany, joerg.kraus{at}salk.at

K Voigt

Research Group for Multiple Sclerosis and Neuroimmunology, Department of Neurology, Justus-Liebig University of Giessen, Giessen, Germany

AM Schuller

Department of Thoracic and Cardiovascular Surgery, Johann-Wolfgang-Goethe University of Frankfurt, Frankfurt am Main, Germany

M Scholz

Department of Trauma and Hand Surgery, Heinrich-Heine University of Duesseldorf, Duesseldorf, Germany

KS Kim

Department of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA

M Schilling

Department of Neurology, University Hospital of Münster, Münster, Germany

WR Schäbitz

Department of Neurology, University Hospital of Münster, Münster, Germany

P Oschmann

Research Group for Multiple Sclerosis and Neuroimmunology, Department of Neurology, Justus-Liebig University of Giessen, Giessen, Germany

B Engelhardt

Theodor Kocher Institute, University of Bern, Bern, Switzerland

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.

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

This version was published on July 1, 2008

Multiple Sclerosis, Vol. 14, No. 6, 843-852 (2008)
DOI: 10.1177/1352458508088940


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