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.

University of Pittsburgh Medical Center

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to