Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Pretreatment increases liver transplant survival in rats

30.06.2003


Pretreating transplanted livers with the immune molecule interleukin-6 (IL-6) dramatically increased survival of rats receiving organs with fatty degeneration--a common condition in humans that typically reduces transplant viability. The results suggest a means of making it possible to use a higher percentage of available donor livers for transplantation in humans. With over three times as many Americans needing transplants as there are available donor livers, an effective approach to increasing the number of viable donor organs would help narrow the gap between demand and supply.

Steatosis, or fatty liver degeneration, is present in between 13 and 50 percent of donor livers. Fat may accumulate in the liver in association with obesity, diseases such as diabetes mellitus, and heavy drinking. Donor livers with steatosis are more likely to function poorly or fail after transplantation. With the increase in obesity in this country, the prevalence of steatosis in donor livers is expected to increase. A multi-center team of scientists found that adding the cytokine or cell-signaling molecule interleukin-6 (IL-6) to the solution in which a donor liver is stored before transplantation significantly increases post-transplant survival of rats receiving organs with fatty degeneration. Bin Gao, M.D., Ph.D., at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), led the scientific team which included investigators at The Johns Hopkins University School of Medicine, Baltimore, MD (supported in part by a research grant from NIH’s National Institute on Diabetes and Digestive and Kidney Diseases) and the University of Science and Technology of China, Hefei, China.

NIAAA Director Ting-Kai Li, M.D. said, "This study is an example of how our knowledge at a molecular level of how the immune system functions to protect against tissue damage can be exploited to develop strategies for dealing with important clinical problems. The work gives us a clue for future treatment and enhances our understanding of the mechanisms of liver damage, and the protection afforded by IL-6, after transplantation."



IL-6, one of the immune system’s complex network of signaling molecules, is known to protect against liver injury in a variety of conditions. In this study, scientists took either healthy livers from lean rats or steatotic livers (livers with fatty degeneration) from genetically obese rats and transplanted them into lean recipient rats. All of the recipients of livers from the lean rats survived (10 of 10). Thirty percent (3 of 10) of the recipients of the steatotic livers stored in standard solution survived. The addition of IL-6 to the preservative solution increased the survival rate of rats receiving steatotic livers to 91.7 percent (11 out of 12). Results were similar whether the organs were stored in the standard preservative used in transplantation (University of Wisconsin or UW solution) or normal saline solution, suggesting that the effect of IL-6 was direct and not the result of interactions with components in the UW solution.

The team compared the post-transplant condition of the organs by microscopic tissue examination (histology) and by measuring levels of liver enzymes that reflect liver function. Steatotic, but not lean, transplanted livers showed massive cell death (necrosis). Steatotic livers preserved in solution with IL-6, however, showed no significant necrosis. Results from liver enzyme tests revealed similar differences: Enzyme levels with IL-6-treated steatotic livers were closer to levels seen in the lean livers and significantly lower than those seen in untreated fatty livers.

The investigators also looked at the mechanisms of tissue damage. Previous research has suggested that after blood circulation is restored to a transplanted liver, loss of cells lining the sinuses of steatotic livers is a key first step in the subsequent damage. Fine capillary blood circulation (microcirculation) is impaired. In both cases, IL-6 protected against these destructive changes.

Cytokines like IL-6 act by setting off a cascade of other signaling molecules. A key effect of IL-6 in particular is activation of a cell survival signal molecule, STAT3. Results from this study confirmed that IL-6 increased and prolonged STAT3 activation. In practical terms, the authors point out, adding IL-6 to a preservative solution before transplantation is likely to require less IL-6 and less likely to cause side effects than giving IL-6 to transplant recipients.

According to the paper, in late 2002, 17,329 American patients were on the United Network for Organ Sharing waiting list for liver transplantation. At the same time, only 5,181 donor organs were available. The increasing rate of obesity in this country could increase, rather than decrease, the shortfall in viable organs.


###
The article by Sun, Z., Klein, A.S., Radaeva, S., Hong, F., El-Assal, O., Pan, H.-N., Jaruga, B., Batkai, S., Hoshino, S., Tian, Z., Kunos, G., Diehl, A. M., and Gao, B. appears in Gastroenterology, Volume 125, pages 202-215, 2003.

For an interview with Dr. Gao, please telephone the NIAAA Press Office.

The National Institute on Alcohol Abuse and Alcoholism, a component of the National Institutes of Health, U.S. Department of Health and Human Services, conducts and supports approximately 90 percent of U.S. research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems and disseminates research findings to science, practitioner, policy making, and general audiences.




Ann Bradley | EurekAlert!
Further information:
http://www.niaaa.nih.gov/

More articles from Health and Medicine:

nachricht Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

nachricht Direct conversion of non-neuronal cells into nerve cells
03.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes

17.07.2018 | Life Sciences

Electronic stickers to streamline large-scale 'internet of things'

17.07.2018 | Information Technology

Behavior-influencing policies are critical for mass market success of low carbon vehicles

17.07.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>