We investigated the effect of several amino acids on the secretion of such inflammatory cytokines as interleukin-8 (IL-8) induced by hydrogen peroxide or tumor necrosis factor-alpha (TNF-alpha) in intestinal epithelial-like Caco-2 and HT-29 cells. We found that histidine, one of the conditionally essential amino acids, significantly inhibited both hydrogen peroxide- and TNF-alpha-induced IL-8 secretion and mRNA expression in Caco-2 cells and HT-29 cells. These inhibitions were dose dependent and the inhibition rate of hydrogen peroxide-induced IL-8 secretion reached more than 50% at a concentration of 25mM, with over 95% inhibition at a concentration of 50mM. TNF-alpha increased the transcriptional activity of the IL-8 promoter which was significantly inhibited by treating Caco-2 cells with histidine. Histidine also abolished the NF-kappaB-dependent activation of the IL-8 promoter induced by TNF-alpha. These results indicate that histidine inhibited the hydrogen peroxide- and TNF-alpha-induced IL-8 secretion at the transcriptional level in intestinal epithelial cells, suggesting that histidine has the potential to attenuate intestinal inflammation.