INCREASED APOPTOSIS OF T-LYMPHOCYTES AND MACROPHAGES IN THE CENTRAL AND PERIPHERAL NERVOUS SYSTEMS OF LEWIS RATS WITH EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS TREATED WITH DEXAMETHASONE

Using light and electron microscopic histological and immunocytochemic al techniques, we investigated the effects of the glucocorticoid dexam ethasone on T cell and macrophage apoptosis in the central nervous sys tem (CNS) and peripheral nervous system (PNS) of Lewis rats with acute experimental autoimmune encephalomyelitis (EAE) induced with myelin b asic protein (MBP). A single subcutaneous injection of dexamethasone m arkedly augmented T cell and macrophage apoptosis in the CNS and PNS a nd microglial apoptosis in the CNS within 6 hours (h). Pre-embedding i mmunolabeling revealed that dexamethasone increased the number of apop totic CD5(+) cells (T cells or activated B cells), alpha beta T cells, and CD11b(+) cells (macrophages/microglia) in the meninges, perivascu lar spaces, and CNS parenchyma. The induction of increased apoptosis w as dose-dependent. Daily dexamethasone treatment suppressed the neurol ogical signs of EAE. However, the daily injection of a dose of dexamet hasone (0.25 mg/kg), which, after a single dose, did not induce increa sed apoptosis in the CNS or PNS, was as effective in inhibiting the ne urological signs of EAE as the high dose (4 mg/kg), which induced a ma rked increase in apoptosis. This indicates that the beneficial clinica l effect of glucocorticoid therapy in EAE does not depend on the induc tion of increased apoptosis. The daily administration of dexamethasone for 5 days induced a relapse that commenced 5 days after cessation of treatment, with the severity of the relapse tending to increase with dexamethasone dosage.