Liver inflammation and cytokine production,but not acute phase protein synthesis, accompany the adult liverprogenitor (oval) cell response to chronic liver injury

Oval cells arefacultative liver progenitor cells, which are invoked during chronicliver injury in order to replenish damaged hepatocytes and bileduct cells. Previous studies have observed inflammation and cytokine productionin the liver during chronic injury. Further, it has been proposedthat inflammatory growth factors may mediate the proliferation ofoval cells during disease progression. We have undertaken a detailedexamination of inflammation and cytokine production during a timecourse of liver injury and repair, invoked by feeding mice a choline-deficient,ethionine-supplemented (CDE) diet. We show that immediately followinginitial liver injury, B220-expressing leucocytes transiently infiltratethe liver. This inflammatory response occurred immediately before ovalcell numbers began to expand in the liver, suggesting that the twoevents may be linked. Two waves of liver cytokine production wereobserved during the CDE time course. The first occurred shortlyfollowing commencement of the diet, suggesting that it may representa hepatic acute phase response. However, examination of acute phasemarker expression in CDE-fed mice did not support this hypothesis.The second wave of cytokine expression correlated with the expansionof oval cell numbers in the liver, suggesting that these factorsmay mediate oval cell proliferation. No inflammatory signallingwas detected following withdrawal of the injury stimulus. In summary, ourresults document a close correlation between inflammation, cytokineproduction and the expansion of oval cells in the liver during experimentalchronic injury.