The commonly held belief is that Interferon-Beta (such as Avonex, Rebif, Betaseron) achieves its beneficial effect on MS progress via its anti-inflammatory properties. This study, however, demonstrates that Interferon-Beta also improves the integrity of the Blood-Brain-Barrier (BBB)-- which generally breaks down in MS patients, allowing increasing amounts of undesirable substances to reach the brain. This strengthening of the BBB might be a contributing factor (if not THE factor?) to Interferon Beta's beneficial effects. Note that this study is in vitro (outside a living organism-- a petri dish experiment), so it does not necessarily mean it works the same in people.
"Multiple sclerosis (MS) is accompanied by a breakdown of the blood-brain barrier (BBB) leading to edema formation and aggravation of the disease...
Taken together, our data demonstrate a direct stabilizing effect of IFN-beta on BBB cerebral endothelial cells in vitro that might significantly contribute to the beneficial effects of IFN-beta treatment in MS in vivo."
Click "read more" for the full abstract...
Advertisement
Full Abstract Text
Interferon-beta stabilizes barrier characteristics of brain endothelial cells in vitro.
Kraus J, Ling AK, Hamm S, Voigt K, Oschmann P, Engelhardt B.
Max-Planck Institute for Physiological and Clinical Research, Department of Vascular Cell Biology, Bad Nauheim, Germany.
Multiple sclerosis (MS) is accompanied by a breakdown of the blood-brain barrier (BBB) leading to edema formation and aggravation of the disease. Interferon-beta (IFN-beta) has been approved for the treatment of MS and besides its immunomodulatory effects has been demonstrated to lead to a stabilization of BBB integrity in vivo. To investigate whether human recombinant IFN-beta exerts direct effects on the BBB, we used an in vitro BBB model in which brain endothelial cells in coculture with astrocytes form a tight permeability barrier for (3)H-inulin and (14)C-sucrose. Removal of the astrocytes from the coculture or alternatively addition of histamine resulted in an increased paracellular permeability for small tracers across the brain endothelial cell monolayer. Strikingly, in the presence of IFN-beta, permeability increase under both conditions was inhibited. Permeability changes were accompanied by minor changes in the staining for tight junction-associated proteins in brain endothelial cell monolayers. Taken together, our data demonstrate a direct stabilizing effect of IFN-beta on BBB cerebral endothelial cells in vitro that might significantly contribute to the beneficial effects of IFN-beta treatment in MS in vivo. Ann Neurol 2004;56:192-205
PMID: 15293271 [PubMed - in process]
