Tumor necrosis factor-${alpha}$ (TNF-${alpha}$) involved in the pathogenesis of multiple sclerosis and contribute to the degeneration of oligodendrocytes as well as neurons. TNF-${alpha}$ is produced by miocroglia and astrocytes, which also produce hormones and cytokines that influence its biological activity. Astrocytes, the major glial cells in the CNS, are capable of producing TNF-${alpha}$ at both the mRNA and protein levels in response to interleukine-1 (IL-1) or TNF-${alpha}$. Two immunosuppressive cytokines, transforming growth factor-${eta}$ (TGF-${eta}$) and IL-10, have been shown to influence glial cell function. TGF-${eta}$ can modulate the activity of glial cells by inhibiting interferon-${gamma}$ (IFN-${gamma}$) induced expression of class II major histocompatibility complex (MHC) molecules on astrocytes and microglia. To explore the role of astrocytes in the production of TNF-${alpha}$, astrocytes were pretreated with IL-10 or TGF-${eta}$ and then stimulated with IL-1${eta}$ to determine their effects on TNF-${alpha}$ production. The secretion of TNF-${alpha}$ by human fetal astrocytes was markedly inhibited by TGF-${eta}$ at a low concentration. In contrast IL-10 had no effect on TNF-${alpha}$ mRNA level. These results show that TGF-${eta}$ may regulate the expression of TNF-${alpha}$ in activated human fetal astrocytes.