Therapeutic worms for inflammatory disorders? Perhaps there is a more palatable option
It is perhaps one of the greatest health triumphs in modern history. In many parts of the world, our remarkable progress in eradicated intestinal parasitic worms has relieved millions from misery and chronic ill health. But many societies that have been successful in eradicating parasitic worms have found themselves burdened with an increasing number of inflammatory disorders like hay fever, asthma, inflammatory bowel disease and eczema.
We are now at a point where more than 3 billion people, nearly half the world’s population, are infected with parasitic worms or suffer from inflammatory disorders. From the evolutionary point of view, this makes sense. Parasitic worms evolved to live alongside us, without killing us, by suppressing part of our immune system called the type 2 immune response.
Natural Immune Suppression
This response allows our body to fight worms and repair the tissue damage they cause. To a certain degree, we evolved to tolerate this suppression by not wasting valuable energy on an all-out war against worms that we are unlikely to win.
In some people, the absence of worms and this natural immune suppression seems to send their type 2 immune response into over drive, attacking harmless particles found in their food or environment and creating chronic inflammation.
Some human studies have raised the intriguing possibility that infection with harmless worms might be able to suppress inflammatory disorders. However, the potential of worm therapy looks like it may be short-lived concept.
Not only would it be grim proposition for many patients, early clinical trials in brave pioneers are showing mixed results. It could be that worms serve only a protective role and can do little to help control a well-established inflammatory disorder.
Despite the risks and lack of evidence, some sufferers of inflammatory disorders still choose to self-medicate with worms. It is seen a last resort for those who have exhausted all other options to control their symptoms and are sorely lacking effective treatments.
Understanding Immune Processes
For this reason, researchers are trying to unravel the mechanisms that underlie the worms’ immune suppression abilities, hoping to reproduce them without resorting to worm therapy. Others are trying to understand how our body reacts to worms in the hope that manipulating these processes will cure the inflammatory disorders that seem arise in those who have never been exposed to worms.
Understanding these basic immune processes is the focus of Dietmar Zaiss’ group at the University of Edinburgh, which I am a part of. We know that during the ‘type 2’ immune response, immune cells, called lymphocytes, travel to the site of infection and release signals, called cytokines, which boost the immune response. Lymphocyte-derived cytokines have deservedly received much attention by scientists hoping to control the degree of immune system activation.
However, manipulating this process could be too blunt an instrument, which could weaken our immune system and leave us vulnerable to other infections. Many inflammatory disorders affect specific organs, such as asthma in our lungs or inflammatory bowel disease in our gut. One of our most intriguing recent discoveries, published in Science, is that the immune response requires other signals, produced only by the surrounding tissue.
These tissue-specific signals are designed to help to fight off worm infections and repair tissue damage. However, if they are not well regulated they can over react leading to allergy and tissue scarring even in the absence of worms. By targeting a local tissue-specific signal instead of a cytokine we could restrict the treatment to a single organ, reducing the likelihood of unwanted side effects.
One of the most important and damaging features of inflammatory disorders is that they follow a seemingly vicious and self-perpetuating cycle. In our most recent paper, published in Immunity, we discovered one possible reason for this.
It seems that tissue injuries themselves, whether they are caused by a parasite or our own immune system’s overreaction to something harmless, trigger pro-inflammatory cytokines. If we could selectively interfere with process that results from the overreaction response we could potentially limit the production of cytokines and reduce the vicious cycle of inflammation.
The insights we have gained are a small step forward in understanding what happens when our ‘type 2’ response goes rogue. Whilst we don’t understand why some people get inflammatory disorders and other don’t, a better understanding of how our immune system drives chronic inflammation could offer researchers new opportunities to develop better, more targeted treatments.
Carlos Minutti, School of Biological Sciences - now at The Francis Crick Institute
Local amplifiers of IL-4Rα–mediated macrophage activation promote repair in lung and liver, Science
Epidermal Growth Factor Receptor Expression Licenses Type-2 Helper T Cells to Function in a T Cell Receptor-Independent Fashion, Immunity