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Clues to life-threatening organ failure (2010)

Relatively little is known about lymph but there is growing evidence that it can carry disease-causing toxins from the intestines throughout the body. Researchers associated with the Maurice Wilkins Centre have conducted the first comprehensive analyses of the proteins that may be involved.

Our tissues and organs are bathed in fluid that provides nutrients and removes waste. Excess fluid from around the body is collected in the lymphatic system and eventually returned to the blood. This fluid, called lymph, contains proteins and other biologically-active factors secreted by the tissues. 

Lymph from the intestine and its mesentery (supporting tissues) takes a unique anatomical route that, in contrast to blood, bypasses detoxification in the liver. Biologically-active factors released by the intestines into the lymph therefore pass directly to the bloodstream, encountering the heart and lungs before being circulated to the rest of the body. 

In the last decade, research has shown that mesenteric lymph can contain toxic factors that contribute to the development of multiple organ dysfunction syndrome (MODS) and other inflammatory diseases. 

Lymph Node BodyMODS is a potentially life-threatening syndrome in which two or more organ systems cannot maintain normal activity without medical intervention.

The precise series of events leading to MODS is unknown, but it typically develops during severe illness such as acute pancreatitis, sepsis or haemorrhagic shock (caused by the rapid loss of large amounts of blood). 

Surgeons and Maurice Wilkins Centre investigators Professor John Windsor and Dr Anthony Phillips from The University of Auckland are leading research examining mesenteric lymph and its role in disease. Their work focuses on identifying proteins and other components in lymph that may provide clues about how critical illnesses develop, and how the conditions might be managed to avoid MODS. 

In 2008 the research team, working with PhD student Anubhav Mittal, published the first description of the full protein complement (proteome) of normal mesenteric lymph, based on animal studies. The researchers then studied changes in two severe illness states. 

Eight of a total of 245 identified proteins in mesenteric lymph were found to be elevated in acute pancreatitis, all but one of which was a pancreatic enzyme. This supports further research into the use of enzyme-blocking protease inhibitors to treat the condition.

The latest study, in 2010, found that sixty proteins increased during hemorrhagic shock. Several of the proteins are worthy of further study, either as contributors to the disease or markers of its severity, suggesting new avenues for its management. 

The studies significantly advance the understanding of lymph composition. The work was made possible by a unique collaboration between surgeons and biologists expert in proteomics, including Martin Middleditch and Professor Garth Cooper of the Maurice Wilkins Centre and by the use of a liquid chromatography-tandem mass spectrometry machine purchased by the Centre.


Image: An artistic impression of the human lymph system