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)‐1β, which was potentiated by interferon (IFN)‐γ and tumor necrosis factor (TNF)‐α. IL‐1 receptor antagonist protein markedly attenuated astrocyte NO production. The anti‐inflammatory cytokines IL‐4 and IL‐10 potently suppressed IL‐1β plus IFN‐γ‐stimulated NO, while transforming growth factor‐β preferentially inhibited IL‐1β plus TNF‐α‐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. © 1995 Wiley‐Liss, Inc.