The Deficiency of Indoleamine 2,3-Dioxygenase Aggravates the CCl.sub.4-Induced Liver Fibrosis in Mice

In the present study, we examined the role of indoleamine 2,3-dioxygenase (IDO) in the development of CCl.sub.4 -induced hepatic fibrosis. The liver fibrosis induced by repetitive administration with CCl.sub.4 was aggravated in IDO-KO mice compared to WT mice. In IDO-KO mice treated with CCl.sub.4, the number of several inflammatory cells and the expression of pro-inflammatory cytokines increased in the liver. In the results, activated hepatic stellate cells (HSCs) and fibrogenic factors on HSCs increased after repetitive CCl.sub.4 administration in IDO-KO mice compared to WT mice. Moreover, the treatment with l-tryptophan aggravated the CCl.sub.4 -induced hepatic fibrosis in WT mice. Our findings demonstrated that the IDO deficiency enhanced the inflammation in the liver and aggravated liver fibrosis in repetitive CCl.sub.4 -treated mice.