Rat liver slices as a tool to study LPS-induced inflammatory response in the liver

Background/Aims: Inflammation in the liver is a complex interaction between parenchymal and non-parenchymal cells, and therefore can not be studied in vitro in pure cultures of these cells. Methods: We investigated whether Kupffer cells in the liver slice are still responsive to an inflammatory stimulus of lipopolysaccharide (LPS), and ev oke an inflammatory response in the hepatocytes. Results: TNF alpha, IL-1 beta and IL-10 were significantly elevated in cult ure medium of LPS-stimulated rat liver slices. Nitric oxide (NO) production of LPS-treated slices gradually increased from 5 to 24 h (24 h: 81 +/- 5 m uM vs. 14 +/- 2 muM in control P < 0.05), paralleled by inducible nitric ox ide synthase (iNOS) in the hepatocytes, iNOS mRNA was induced after 3 h. NO production but not iNOS induction was significantly inhibited by NOS inhib itors S-methylisothiourea and N-G-nitro-L-arginine methylester. Both pentox ifylline and dexamethasone inhibited TNF alpha and IL-1 beta production, al beit to a different extent, iNOS induction and, as a result thereof, NO pro duction. Conclusions: These results imply that non-parenchymal cells in liver slices are viable and can be activated by LPS. In addition, it is concluded that the upregulation of iNOS in hepatocytes by LPS is caused by cytokines produ ced by Kupffer cells because inhibition of TNF alpha and IL-1 beta producti on attenuated iNOS induction. (C) 2001 European Association for the Study o f the Liver. Published by Elsevier Science B.V. All rights reserved.