Interleukin-10 (IL-10) inhibits tumor necrosis factor (TNF) production. We investigated the role of endogenous IL-10 in brain TNF production. We injected IL-10-knockout mice with lipopolysaccharide (LPS,2.5 microg/mouse i.c.v.). Brain TNF and IL-6 levels were more elevated and persisted longer in IL-10-deficient mice compared with wild type mice, suggesting that IL-10 is an important negative feedback inhibitor of TNF and IL-6 production in the CNS.