Differential tumor necrosis factor alpha expression by astrocytes from experimental allergic encephalomyelitis-susceptible and -resistant rat strains

There are reports suggesting a causal relationship between rytokine production and disease development . LPS-induced TNF-a production by macrophages from the autoimmuneprone NZB x NZW Fl strain is significantly less than that from MHC-matched normal mice, and the administration of TNF-a protects this strain from developing lupus nephritis (50) . These data suggest that depressed production of TNF-a may contribute to development of autoimmunity. In contrast, Boswell et al . (51) found that local production of TNF-a by kidney macrophages may accelerate renal disease in MRIT lpr mice. These differences may reflect the different strains of mice under study. Overproduction of TNF-(x plays a central role in the pathogenesis of cerebral malaria, as in vivo treatment with antiTNF antibody prevents disease (52) . An association of TNF-a with MS is suggested by the observation of TNF-a-positive astrocytes in the MS brain (53). A recent report by Ruddle et al . (54) demonstrated that an antibody to TNF-a/lymphotoxin could prevent the transfer of EAE by encephalitogenic T cells . These findings indicate that inhibition of the biological activities of these two cytokines could prevent neurological disease, although the mechanism(s) of action is as yet unknown . Thus, a number of in vivo and in vitro studies implicate TNF-a and the cells that produce it as contributors to both the initiation and perpetuation of EAE .