Wasaki S, Sakaida I, Uchida K, Kimura T, Kayano K, Okita K
Department of Internal Medicine, Yamaguchi University, School of Medicine, Yamaguchi-Prefecture, Japan.
Liver. 1997 Apr;17(2):107-14. doi: 10.1111/j.1600-0676.1997.tb00790.x.
We examined the effect of cyclosporin A (CsA) on the pathogenesis of acute experimental liver injury in rats induced by injection of heat-killed Propionibacterium acnes (P. acnes) and subsequent injection of lipopolysaccharide (LPS). Pretreatment with CsA significantly reduced serum alanine aminotransferase (ALT), serum tumor necrosis factor-alpha (TNF-alpha) production, without changing the TNF-alpha mRNA level in the liver, and plasma interferon-gamma (IFN-gamma), following LPS injection in this model. Twenty-four-hour mortality was also markedly improved, from 100% in the P. acnes plus LPS group to 0% in the CsA-pretreated group. Although direct addition of CsA to isolated hepatic macrophages from P. acnes-pretreated rats did not prevent the production of TNF-alpha and active oxygen species, isolated hepatic macrophages from P. acnes plus CsA-pretreated rats significantly reduced their production in response to the addition of LPS. These results suggest that CsA protects against P. acnes plus LPS-induced acute liver injury, not by direct inhibition of hepatic macrophage activation, but by indirect prevention of hepatic macrophage activation, presumably related to the reduction in plasma IFN-gamma levels.
