Studies increasingly indicate that inflammation induced by beta-amyloid (A beta) contributes to the progression of Alzheimer's disease (AD). How to inhibit the enhanced production of proinflammatory cytokines stimulated by All is an important research subject for the treatment of AD. In this study, we investigated the inhibitory effect and the molecular mechanism of the lipoxin A(4) (LXA(4)) on the production of interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) induced by beta-amyloid in the cortex and hippocampus of mice, and in A beta-stimulated BV2 cells, a mouse microglial cell line. LXA(4) down-regulated the protein expression of IL-1 beta and TNF alpha, attenuated the gene expressions of IL-1 beta and TNF alpha, inhibited the degradation of I kappa B alpha inhibited translocation of NF-kappa B p65 subunit into the nucleus induced by beta-amyloid in the cortex and hippocampus of mice, and in A beta-stimulated BV2 cells, and the inhibitory effects were dose dependently elevated. Our findings suggest that LXA(4) inhibits the production of IL-1 beta and INF alpha induced by beta-amyloid in the cortex and hippocampus of mice, and in BV2 microglial cells via the NF-kappa B signal pathway. (C) 2011 Elsevier Inc. All rights reserved.