A REDUCTION IN SERUM GLUCOCORTICOIDS PROVOKES EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS - IMPLICATIONS FOR TREATMENT OF INFLAMMATORY BRAIN DISEASE

Glucocorticoid (GCC) therapy usually inhibits inflammatory diseases, b ut certain regimens can trigger relapses. Clinical use of steroids is not uniform and in some instances may be dangerous. In the present stu dy, GCCs modified the course of experimental allergic encephalomyeliti s (EAE) in Lewis rats, a model of inflammatory CNS disease. Continuous treatment with dexamethasone (DEX) completely blocked EAE. RU 486, a GCC antagonist, counteracted the effects of endogenous GCCs and worsen ed EAE. Sudden withdrawal of DEX also caused severe clinical and histo logic exacerbations at a time when paired saline-treated animals had c ompletely recovered. In rats that had complete clinical recovery from EAE, and would not have relapsed without this acute steroid deficit, a short pulse of DEX was followed by severe exacerbations. In contrast, a slow steroid taper prevented exacerbations. Abrupt discontinuation of GCCs provokes inflammatory brain disease.