Thursday January 29 2009
Hookworms are being used in new trials on the immune system
Infecting patients with worms ”could hold key to treating asthma and other conditions on the rise because of the modern obsession with cleanliness,” The Daily Telegraph reports. The newspaper said that scientists now believe the elimination of worm infections in developed countries might explain why some illnesses, such as asthma and diabetes, are becoming more common.
The theory behind this claim is that over thousands of years the human immune system has adapted to cope with widespread parasite infections, and now that these have been virtually wiped-out in the West, our immune systems are unbalanced.
This news story was based on the publication of three large scientific reviews on parasitic worms and the immune system, which point to an expanding area for future research. Several trials are currently underway in Nottingham, Cambridge and London looking at how worm use might get the modern immune systems back in balance. If these are successful, researchers hope that drugs could be developed to help boost the immune system and treat allergies such as asthma.
Where did the story come from?
Professors Graham Rook, Anne Cooke and Jan Bradley are the senior authors of these three separate review papers addressing the possible role of parasitic worms in immunology. They were based on work conducted at The Windeyer Institute of the Royal Free and University College London Medical School, The University of Cambridge and The Universities of Nottingham and Liverpool, respectively.
The studies were funded by a variety of research grants from institutions including The Wellcome Trust, The Royal Society, The Natural Environment Research Council and the European Commission.
All three studies were published consecutively in Immunology, a peer-reviewed medical journal.
What kind of scientific study was this?
The papers were three separate reviews that summarised the current state of knowledge about parasitic worms (those known as helminthes), the immune system, immune diseases and the theories about hygiene. While these papers were published together, they are separate reviews conducted by the senior authors.
They looked in detail at how infection with worms might affect the onset of type 1 diabetes in mice, and the theories of how the immune response generated by worms might have evolved.
Helminthes are a group of worm-like parasites with similar characteristics but varying origins. Helminthes are categorised into three broad groups: the platyhelminthes (tapeworms and flukes), the nematodes (roundworms) and the acanthocephalans (thorny-headed worms).
There are many different species and these can affect different organ systems in the human, e.g. eyes, blood, liver, intestine, brain, muscle lungs and skin. Some helminth infections can cause serious health problems, while others may be relatively minor.
The hygiene hypothesis
The first paper, by Professor Rook, describes the background theory of this story, reviewing evidence for the ‘hygiene hypothesis’. This theory proposes that the relatively rapid move from the hunter–gatherer environment to the living conditions of the rich, industrialised countries may have led to a reduced pattern of exposure to microorganisms. In turn, this hygiene may lead to a disordered regulation of the immune system, and finally to increases in certain inflammatory disorders.
This idea was first applied to allergic disorders such as asthma, but Professor Rook believes that it can be applied to other diseases too, such as autoimmune conditions, inflammatory bowel disease, some nerve disorders, hardening of the arteries, depression and some cancers.
In this review, Professor Rook discusses these possibilities in the context of evolution, suggesting that it might be possible to exploit these parasitic organisms (such as helminthes) or their components to stimulate the immune system and develop new therapies.
Helminthes and type 1 diabetes
The second paper, by Professor Cooke, gives a specific example of helminth use applied to the development of type 1 diabetes.
Type 1 diabetes, a type that usually requires insulin, is influenced by both genetic and environmental risk factors. The current rise in the incidence of diabetes is thought to be occurring more rapidly than can be accounted for by genetic change alone, highlighting the influence environmental factors might also have.
Previous studies have looked for, but not found, a single infectious cause for developing type 1 diabetes. The author reviews research into how some infections of historical importance may play a role in reducing the rates of some autoimmune and allergic disorders.
In particular, one study by Professor Cooke has shown that infection with the worm known as schistosoma mansoni could prevent the development of type 1 diabetes in mice that are genetically engineered to be more prone to the condition.
Evolution and the immune system
The third paper, by Professor Bradley, looks at the specific molecules found in worms, in mud and in the tiny organisms (flora) in the gut. It also looked at the white blood cells that the immune system produces in response to worm infections. Theoretically this white blood cell production could lead to beneficial health effects.
Two immune system cells that increase or decrease in a characteristic response to these worms are the T-helper type 2 (Th2) cells and regulatory T-helper (Treg) cells. The relationship between the Th2 responses and wound-healing is discussed in the paper.
A theory on how helminth immunity is controlled is also discussed from an evolutionary perspective. For several thousand years people in ancient societies had permanent worm infections from animal interaction.
It is suggested that over these thousands of years human immune systems developed around worm infections, but with the eradication of helminth worm infections in modern humans our immune sytems are now ‘maladapted’, and can no longer regulate themselves correctly.
What conclusions did the researchers draw from these reviews?
The hygiene hypothesis
After discussing several related disorders, Professor Rook concludes by saying, “It is clear that this area is worth exploring in detail because unravelling the mechanism of the action of [the worms] at the molecular level might lead to new drugs for [prevention] and treatment in many areas of medicine.”
Helminths and type 1 diabetes
Having discussed the selected studies investigating development of type 1 diabetes, Professor Cooke says that, “it is now clear from a range of studies that the development of diabetes in some mice can be inhibited by several different infectious agents [the worms] but not by all infections”.
The timing of infection is also important with some infections being able to inhibit the onset of diabetes only if they occur before the worms infiltrate the pancreas. However, this is not the case when mice are infected with a particular worm called S. typhimurium. Here, the worm protects the mouse against diabetes only once the pancreas has been infiltrated.
The author hopes that by identifying the ways in which the worms affect immunity, it will become possible to develop new therapies that may not require infection with a live worm.
Evolution and the immune system
The future of this molecular level research is discussed by Professor Bradley and he concludes that this is an important area where there is an urgent need for laboratory model studies looking at the effects of de-worming.
What does the NHS Knowledge Service make of this study?
These three studies have reviewed a vast body of knowledge in the fields of immunobiology, parasitology, medical microbiology, immunology and evolutionary medicine. They have the potential to change the way people think about worm infections, and also point the way for further research.
Any potential treatments to prevent type 1 diabetes in humans may be a long way off, as the safety and practical concerns of human treatment remain and must be resolved first.
Professor Rook says, "It now looks more and more likely that the development of our regulatory immune system depends on molecules that are encoded not in the genome of the human but in the genome of some other organism we lived with throughout history." The genome (genetic code) of these other organisms will no doubt be studied in further detail.