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


CONCLUSIONS
Our data suggest that BBB stabilization by IFN-beta-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.
Kraus
J
J
Department of Neurology, Paracelsus Private Medical University, Salzburger Landesklinken, Christian-Doppler-Klinik, Salzburg, Austria. joerg.kraus@salk.at
Voigt
K
K
Schuller
A M
AM
Scholz
M
M
Kim
K S
KS
Schilling
M
M
Schäbitz
W R
WR
Oschmann
P
P
Engelhardt
B
B
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000276:immunology; D002199:Capillary Permeability / Q000187:drug effects / Q000276:immunology; D002417:Cattle; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000494:pharmacology*; D051379:Mice; D051381:Rats; D013045:Species Specificity; D013552:Swine
D000276:Adjuvants, Immunologic; D017442:Histamine Agonists; D016899:Interferon-beta; D006632:Histamine; D000068556:Interferon beta-1a