Giving allergies a good name

ANYONE who has suffered from hay fever would support the view that allergies are bad news. But the allergic reaction is not necessarily a bad thing if you are an animal trying to shed liver fluke. A similar view of the irritation of diarrhoea - that it is not always an affliction - holds true for at least one researcher at UCD.

Decian McCole, joint winner of the first Merville Lay Seminar lecture series, challenged the audience, stating that he intended to "disprove two commonly held beliefs" that allergies and diarrhoea were bad. He is completing a PhD research project for UCD's departments of pharmacology and veterinary medicine. The subject under discussion was how cattle defend themselves against liver fluke.

"The research was an investigation into how the gut works," he said. More particularly it was an examination of how the gut responds to the presence of liver fluke. Liver fluke parasites are ingested and travel through the stomach to the intestine, burrowing through the lining of the gut and reaching the liver.

Current treatment regimes, McCole explains, involve either trying to kill the fluke in the field before it is eaten by cattle or by treating the animal when flukes are in the "liver. It is estimated that the parasite costs the Irish economy about £100 million annually in decreased milk yield, reduced weight gain and treatment.

McCole's work focused on how the gut responded to fluke as a way to identify other treatment possibilities. "Our interest lies in trying to influence the intestine and its immune system into exerting a greater level of protection against infection than that which is found with current treatment strategies," he explains.

During an initial infection the animal's immune system recognises the invader but is unable to prevent the parasite from reaching the liver. An initial exposure, however, primes the immune system so a response is triggered during subsequent infections. And the response is diarrhoea and an allergic like reaction, hence McCole's initial premise.

If the primed immune system detects fluke, it releases chemical substances known as mediators which act on the cells that line the gut. They stimulate these cells to pump out water in an attempt to flush out the flukes.

"The cells of the immune system which are involved would include those that are normally associated with allergy - thus showing how allergy can prove beneficial to the body by protecting it against infection by a parasite.

This mechanism had been demonstrated in rat models and McCole wanted to establish whether the response was also seen in cattle. The first step involved infecting eight cattle with fluke. After 14 days the animals were killed and sections of large intestine removed. There was also a control group of animals which underwent a wide range of tests to ensure they had no previous liver fluke infection. One of the tests on the controls involved sifting through cattle faecal samples to detect liver fluke eggs. As he so neatly put it, "you can imagine this was a particular highlight of the study."

The next step was to take living tissue samples, keeping them alive in an oxygen containing solution. The apparatus used to hold the tissues was also able to measure the movement of sodium and chloride ions across the cells. When ions move across a piece of intestine, this is always followed by the movement of water.

"Therefore," explains McCole, "this piece of equipment allows us to assess whether the challenge (by fluke) of previously infected intestine is likely to induce the symptoms of diarrhoea, that is movement of water across the intestine." The challenge was delivered in the form of ground up liver fluke. These fluke would obviously contain the constituents recognised by the animal's immune system.

When this material was placed into the apparatus with the tissue taken from infected animals, there was a rapid increase in movement of ions and water across the cells. There was a complete lack of response in uninfected animals.

THE NEXT STEP was to examine the cells involved in the water response. If it was an allergic reaction, as it appeared, then a particular group of immune cells would be involved. This had been shown to be the case in rat models, but McCole's work showed for the first time that the same held true for cattle, that cells associated with allergy were involved.

This suggests that perhaps a treatment could be developed to artificially sensitise the host, not by infection but by vaccination. This would cause the animal to experience a protective dose of diarrhoea whenever it encountered fluke.

Another important result from McCole's work was the development of a test system to assess what part of the ground up liver fluke was likely to achieve the best vaccine response.

McCole was responsible for all lab work including the development of the test systems. He had three supervisors, Dr Alan Baird of pharmacology, and Drs Paul Torgerson and Michael Doherty, both of veterinary science.

Participation in the Merville lectures was interesting. "The main thing was trying to keep it simple without being patronising," said McCole.