Glucocorticoid and type I interferon interactions at the blood-brain barrier: relevance for drug therapies for multiple sclerosis

The pharmacological effect of glucocorticoids and type I interferons (IFNs) , simultaneously used as therapeuticals for multiple sclerosis (MS), on the (inflamed) blood-brain barrier (BB) was investigated in vitro. Although bo th drugs additively decreased BBB permeability, they did not prevent the in crease in BBB permeability induced by lipopolysaccharide (LPS), which serve d as a pro-inflammatory stimulus. The beneficial clinical effect of glucoco rticoid and IFN therapy for MS seems therefore not to be mediated through a direct action at the level of the BBB. Most strikingly, however, pretreatm ent with type IFNs (alpha and beta) potentiated the effect of glucocorticoi ds by two orders of magnitude. This lead us to hypothesize that type IFNs m ay restore the dysfunctional T-helper I (Th1)/Th2 balance associated with M S, by a mechanism that involves an increased sensitivity for glucocorticoid s. NeuroReport 12:2189-2193 (C) 2001 Lippincott Williams & Wilkins.