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 both drugs additively decreased BBB permeability, they did not prevent the increase in BBB permeability induced by lipopolysaccharide (LPS), which served as a pro-inflammatory stimulus. The beneficial clinical effect of glucocorticoid and IFN therapy for MS seems therefore not to be mediated through a direct action at the level of the BBB. Most strikingly, however, pretreatment with type IFNs (alpha and beta) potentiated the effect of glucocorticoids by two orders of magnitude. This lead us to hypothesize that type IFNs may restore the dysfunctional T-helper I (Th1)/Th2 balance associated with MS, by a mechanism that involves an increased sensitivity for glucocorticoids. NeuroReport 12:2189-2193 (C) 2001 Lippincott Williams & Wilkins.