Cytokine regulation of iNOS expression in human glial cells

In this report, we review the evidence for the production of nitric oxide following cytokine activation of the inducible form of nitric oxide synthase by central nervous system glial cells, with particular reference to cells of human origin. The results suggest that cytokine regulation of this enzyme in human glial cells differs significantly from that found in cells of rodent or murine origin, with astrocytes rather than microglia being the major source of these products in inflamed nervous system tissue. The key activator of this enzyme in human astrocytes is IL-1 with IFN-γ acting synergistically. In contrast to glial cells of rodent or murine origin, no down-regulatory effects were noted with the cytokines IL-4, IL-10, and TGF-β. The relevance of these data to human neuropathology is discussed.