Can serum cytokines predict hepatic cytokine expression in liver cirrhosis?

Cytokines are involved in liver injury and cirrhosis. However, studies to explore whether systemic and hepatic cytokine levels can help in predicting cirrhosis progression are limited. Common bile duct ligation (BDL) is a well-established animal model used to induce cholestatic liver injury with inflammation, fibrosis, and cirrhosis. The study by Hsieh et al study is characterized by a systemic approach to evaluate the overall picture of hepatic and circulating cytokines, including IFN-g, TNF-a, IL-10 and TGF-b, during cirrhosis development. Their study shows that cirrhosis development is associated with progressively enhanced hepatic proand anti-inflammatory cytokine expression in BDL rats. However, corresponding serum concentrations were not completely in accordance with hepatic cytokine expression in BDL rats. Hsieh et al conclude that circulating cytokine concentrations may not totally reflect their hepatic expression levels during the development of cirrhosis. The roles of cytokines, which may be responsible for initiation and progression of hepatic injury, fibrosis and cirrhosis, but can also participate in liver regeneration, are complicated in hepatic damage. Elevated circulating TNF-a has been observed in patients with alcoholic liver disease, especially those who are malnourished, and has been correlated with survival. Increased circulating TNF-a has been reported in patients with viral hepatitis. Hepatic expression of TNF-a is upregulated in autoimmune liver disease, alcoholic hepatitis and cirrhosis. Hsieh et al observed that hepatic TNF-a expression rather than serumTNF-awasmarkedly elevated inBDL rats. A previous study suggested that TNF-a plays a central role in hepatic regeneration following both toxic and partial hepatectomy. Exogenous TNF-a stimulates hepatic DNA synthesis in rodents and accelerates recovery of liver weight following partial hepatectomy. Hepatic regeneration following chemically induced hepatotoxicity is also impaired in TNF type 1 receptor knockout mice and following anti-TNF-a antibody administration. In fact, Kupffer cell blockade augments hepatic regeneration following partial hepatectomy secondary to impaired IL-10 release from these cells, which allowed sustained unopposed TNF-a production from endothelial cells. Hsieh et al observed that the trends for serum TNF-a changes were not consistent with those for hepatic TNF-a expression levels, which suggests that measurement of serum TNF-a cannot reflect hepatic TNF-a expression. Previous studies revealed that hepatic IFN-g mRNA correlated with the degree of liver damage. Natgonat et al reported