ASTROGLIAL OVERPRODUCTION OF TGF-BETA-1 ENHANCES INFLAMMATORY CENTRAL-NERVOUS-SYSTEM DISEASE IN TRANSGENIC MICE

Cerebral expression of the injury response cytokine transforming growt h factor-beta 1 (TGF-beta 1) has been found to be increased in several neurological diseases but it remains unclear whether its function is primarily beneficial or detrimental. Here we show that transgenic (tg) mice that overexpress bioactive TGF-beta 1 in the central nervous sys tem (CNS) and show no overt phenotype in the unmanipulated state, are more susceptible to the immune-mediated CNS disease experimental autoi mmune encephalomyelitis (EAE). TGF-beta 1 tg mice with EAE showed an e arlier onset of clinical symptoms, more severe disease and increased m ononuclear cell infiltration in their spinal cords compared with non-t g littermate controls with EAE. Whereas previous observations indicate d that increased peripheral levels of TGF-beta 1 can suppress EAE, our findings demonstrate that local expression of TGF-beta 1 within the C NS parenchyma can enhance immune cell infiltration and intensify the C NS impairment resulting from peripherally triggered autoimmune respons es. (C) 1997 Elsevier Science B.V.