D-Galactosamine (GaIN) induces acute hepatitis in experimental animals and this hepatitis has been shown to be suppressed by preceding ingestion of amino acids such as Gly, L-Ser, and L-GIn. However, little is known about the mechanism of its action. The present study shows for the first time that IL-18 reduction is involved in the suppressive actions Of L-GIn and L-Ser on GaIN-induced hepatitis. Elevation of IL-18 mRNA expression in liver and its concentration in serum in GaIN-treated rats were found to be suppressed by preceding ingestion of 10% L-Gln- or 10% L-Ser diets, and resulted in the attenuation of the increase in serum transaminase (ALT and AST) activities, indexes of hepatic injury. These results suggest that suppressive effects of some dietary amino acids on the GaIN-induced hepatitis are mediated by IL-18 reduction. (c) 2008 Elsevier Inc. All rights reserved.