University Of Pittsburgh Researchers Identify Immune System Process That Could Halt Progress Of Cirrhosis In Humans

April 18, 1999

WASHINGTON, D.C., April 18 -- Results of animal laboratory studies conducted at the University of Pittsburgh's Thomas E. Starzl Transplantation Institute dispel the notion that interleukin-6 (IL-6) causes liver fibrosis or cirrhosis and instead suggest that it is important to the liver's recovery. So encouraged is the research team by these findings, being presented at today's sessions of Experimental Biology '99, that it plans to initiate further studies to determine if IL-6 can slow liver disease progression in patients.

IL-6 is a cytokine, a chemical substance secreted by immune system cells. Because it is elevated in a number of diseases, including those of the liver, its presence has been thought to be a contributing factor to, or a feature of, the disease process. The University of Pittsburgh's research indicates the immune system's release of IL-6 must be part of an effort to preserve hepatocytes, or liver cells, and are not an accomplice to their demise. In cirrhosis, the liver becomes inflamed and takes on a lumpy appearance as hepatocytes die, but other cells, such as fibroblasts and bile duct cells, proliferate.

The Pitt researchers made their discovery, an outcome that proved their own study hypothesis wrong, after a series of experiments with groups of mice either capable or incapable of producing IL-6. A model of cirrhosis was created by tying off the common bile duct. The researchers assumed the mice that could make IL-6 would fare worse, but in fact the opposite was true. The mice that could not produce IL-6 had more pathological and clinical evidence of cirrhosis, including fewer hepatocytes and higher bilirubin levels, and had a mortality rate twice that of the IL-6-producing mice.

"IL-6 is important to maintain hepatocyte mass, liver architecture and function during persistent injury," reports Tsukasa Ezure, M.D., the study's first author.

The team is designing studies whereby adult patients with various liver diseases, including sclerosing cholangitis and biliary cirrhosis, or children with biliary atresia, would receive doses of growth factors, such as IL-6, or another substance called hepatic growth factor, to determine if the progression of their disease could be halted or even improved.

"Concerning IL-6, the concept is correct, at least in animals. We're optimistic as we initiate clinical studies, but there's always concern when you take the leap from animal laboratory to the clinical setting," says Anthony J. Demetris, M.D., senior investigator of the study, who is professor of pathology and director of transplant pathology at the University of Pittsburgh.

In addition to Drs. Ezure and Demetris, other authors include: Toshiki Sakamoto, M.D.; John G. Lunz, III; Shigeki Yokomuro, M.D.; Hirokazu Tsuji, M.D., Ph.D.; Noriko Murase, M.D.; and John J. Fung, M.D., Ph.D.
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University of Pittsburgh Medical Center

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