Published by Australian Academy of Science
The rise and rise of asthma Box 2 | Australian research

Finding out more about the reasons why allergic (extrinsic) asthmatics react so strongly to their allergic triggers is being studied by two Australian research teams: one headed by Dr Paul Foster at the John Curtin School of Medical Research at the Australian National University in Canberra; the other headed by Professor Colin Sanderson at the TVW Telethon Institute for Child Health Research in Perth.

One of the great mysteries of the allergic type of asthma – or indeed of any allergic condition – is why the body makes such a fuss over totally harmless airborne particles. We know that what we call allergens are simply materials mistaken for invading microbes or their products. It’s a costly mistake: the entire immune system is put on red alert to counter a non-existent threat, and the result is the gamut of symptoms that sufferers must endure. But why? Grass pollen or mite faeces should not be genuine problems for the human body; after all, the majority of people don’t react to them at all.

Eosinophils respond to allergens in asthmatics

Researchers know that the chief culprit in causing much of the damage in an asthma attack is a fairly rare type of white blood cell called the eosinophil. Eosinophils are designed to be the ‘heavy force’ of the immune system, being equipped to deal with occasional 'big' invaders such as worms. It seems quite bizarre, but in asthmatics these cells are unleashing their strong destructive power onto the patient’s uninfected tissue without any provocation.

Perth research on interleukins

Why and how are the eosinophils brought into the airways and lungs by allergens? In 1985, a team in London discovered that interleukin (an immune system molecule) was controlling eosinophil production and decided to study it. The head of the team was Professor Colin Sanderson. When he came to Perth in 1993, the project moved with him. Research showed that there were actually two chemical messengers involved in eosinophil control. These are now called interleukin-4 (IL-4) and interleukin-5 (IL-5). (The latter was what Colin Sanderson first identified.) These signalling molecules are secreted into the bloodstream by other cells of the immune system (T cells), and can attract eosinophils to the area. If we could block the release of the interleukins, it might stop the accumulation of eosinophils and many of the resulting symptoms of an asthma attack.

The researchers in Perth are finding out what controls the production of IL-5 itself. The aim is to see if there are differences in the regulation of its production between T cells from normal and asthmatic individuals. Preliminary findings suggests that there are differences.

Canberra researchers use genetically engineered mice

At the Australian National University in Canberra, Mr Simon Hogan, a PhD student in Dr Foster’s team, has developed a ‘mouse model’ of allergic asthma. From these asthmatic mice, Dr Klaus Matthaei and Professor Ian Young, also at the John Curtin School, genetically engineered varieties of mice that lacked the genes for expression of either IL-4 or IL-5. When tested with the usual triggers, it was found that the asthmatic mice that couldn’t make IL-5 didn’t have any eosinophils in their airways and lung tissue, and they showed none of the contraction of the smooth muscle of the airways that characterises a full-blown asthma attack. Although they had some types of white blood cell accumulating, they were virtually symptom-free. But the mice that could not make IL-4 had asthma symptoms, which suggested that this chemical messenger is not as important for controlling eosinophils as IL-5.

In a further refinement, designed to prove IL-5’s involvement once and for all, colleague Dr Alistair Ramsay was asked to build a genetically engineered virus to carry the IL-5 gene back into the lungs of the mice lacking IL-5. When the mice were infected with the virus, and Il-5 was synthesised, an allergic trigger produced a full asthma response in mice that previously had produced none when presented with an identical trigger.

Applications of the research

The knowledge from this work gives us a way out of the asthma maze. Blocking the release of IL-5 or inhibiting its effects – such as through a drug that binds to it and inactivates it – could be extremely useful.

The Perth team is now seeking ways of testing for substances that could be used to inhibit IL-5 production or to inactivate circulating Il-5. The Australian pharmaceutical company AMRAD, in Melbourne, will carry out the process of screening likely candidates.

Related sites

• The asthma puzzle (Australia Advances, CSIRO) (requires QuickTime)

• Cytokine Molecular Biology and Signalling Group (John Curtin School of Medical Research, Canberra)

• The modulation of allergic airways disease by Interleukin-4 and -5: Studies using cytokine deficient mice (McMaster University, Canada)

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