Differential regulation by cytokines of human astrocyte nitric oxide production

Reactive nitrogen intermediates, such as nitric oxide (NO), play an important role in host-defense and injury. Human astrocytes released abundant NO upon stimulation with the pro-inflammatory cytokine interleukin (IL)-1 beta, which was potentiated by interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. IL-1 receptor antagonist protein markedly attenuated astrocyte NO production. The anti-inflammatory cytokines IL-4 and IL-10 potently suppressed IL-1 beta plus IFN-gamma-stimulated NO, while transforming growth factor-beta preferentially inhibited IL-1 beta plus TNF-alpha-stimulated production of NO. These findings suggest that while IL-1 plays a key role in inducing astrocyte NO production, anti-inflammatory cytokines have the capacity to downregulate NO production by IL-1-stimulated astrocytes.