Worms against allergies and autoimmune diseases?

Healing... worms?Tatiana Tikhomirova, allergist-immunologist, Ph.D.

ABC Magazine

How simple and understandable it was to live earlier, for example in the eighties. We iron diapers on both sides, boil nipples and toys, water too, but of course. We bathe the child almost in potassium permanganate, so that no infection sticks. Well, if you scald vegetables and fruits with boiling water before eating, then you can immediately say - the right, caring mother. And at school, do you remember the attendants? Who with red armbands stand at the entrance to the dining room and check the cleanliness of their hands? And checking the cleanliness of the feet in the pioneer camp? Cleanliness is the key to health!

Only a little later, having collected money for the treatment of poor African children, they discovered a strange thing: it is worth treating them, proglistogon and bringing them into a clean civilized form – an allergy begins. The doctors left, the children ate the earth again, returned to the usual diarrhea, got infected with worms – the allergy recedes. Doctors came to treat, wash and disinfect – allergy again ... why would I?

And the hygiene hypothesis explains this oddity. At first, doctors drew attention to a serious increase in allergic and autoimmune diseases in developed countries. Environmental pollution and various chemicals? OK, but then how to explain that children from poor neighborhoods in the same countries, where pollution and chemicals are much more, have fewer allergies than children from their rich neighborhoods, where there is fresh air outside the window, and on the menu there are environmentally friendly naturally selected large brown chicken eggs from chickens kept freely and without cages? It doesn't fit.

Maybe genetic differences between different races and nationalities? OK, but then how to explain that the kids who remained in Pakistan do not know about any allergies, and their peers from parents who moved to England, in the first generation, get sick with the same frequency as native Englishmen? It doesn't fit again. And finally, African observations that showed in almost real time that getting rid of parasites causes an increase in allergies.

The hygienic hypothesis explains all this by the fact that at an early age the body must go through intestinal infections and get acquainted with the main parasites, repeating the path that has been programmed in the immune system for tens of thousands of years. Then the immune system adapts normally, adjusts and is regulated. If there are no infections and parasites in the child's environment, then the immune system does not find material for training and tuning, which leads to an erroneous reaction to harmless substances (allergies) or aggression on its own cells, tissues and organs (autoimmune diseases).

If this hypothesis is correct, then it turns out that it is possible to treat allergies and autoimmune diseases by specifically infecting the patient with parasites?

Animal modelsBefore infecting volunteers, we still need to study the question deeper, for which we have laboratory animals, which is what scientists have done.

Recently, Cell Press (or rather, Trends in Parasitology Vol.25 No.3, 109-114) published a review reviewing the results of these numerous experiments.

The results are quite unambiguous: infection with helminths treats allergies, reduces inflammatory changes in models of autoimmune diseases, reduces the sensitivity of animals to allergens.

But the results obtained in animal models have some limitations. First of all, mice and rats themselves do not suffer from autoimmune diseases, and for a model of diabetes or Crohn's disease, it is necessary to chemically or mechanically damage the target organ, and to obtain an asthma model, special provocations need to be made. Or use animals in which some mechanism of immunity is genetically "broken", which leads to the spontaneous development of the same diabetes or allergy. That is, the model is, of course, good, and the symptoms are the same, and there are not many other possibilities, only there is never a 100% correspondence with a similar state of the human immune system.

The second limitation, mentioned more than once in serious reviews: imagine that you created a model, worked with it for a whole year, and in the end did not get anything. And the dependence on infection with worms is unclear, and the data between the main and control groups do not differ much.

Will you publish it, will you be able to? Probably not. It turns out that all the works that have already appeared in print can only be the "tip of the iceberg", which is based on ten times more unsuccessful experiments that showed "something is wrong" or "nothing". Unfortunately, there is no getting away from these shortcomings of animal models. For example, in a bunch of papers they found that a cytokine called interleukin-10 is something that increases from infection with helminths and causes a therapeutic effect, they began trying to treat patients with this cytokine, and – no result. It's sad, but this is life.

But still, animal models have already given mankind a bunch of medicines and helped to find out in detail how many diseases develop. The same models also helped to understand the details of how helminths can treat allergies and autoimmune diseases.

Possible mechanism of therapeutic action of helminthsSo, helminths treat allergies in approximately the following way.

Since the parasite does not want the immune system to quickly calculate and destroy it, it tries to protect itself by causing an increase in anti–inflammatory molecules - it has been established that at least these are TGFb (transforming growth factor) and interleukin-10 (IL-10), which I already mentioned above.

These molecules are important for special cells of the immune system: regulatory T cells, or in professional jargon, Tregs. Each of us has tregs, and their task is to limit and stop the activation of the immune system. That is, they work as a safety valve, restraining excessive immune reactions.

If the Tregs are weak, then once an immune response to an infection will kill not only the pathogen, but also destroy a bunch of healthy cells and tissues around, and it's not a fact that it will stop after that. If the Tregs are too strong, then they can mistakenly protect cancer cells, preventing their destruction, or they can protect the parasite, preventing the immune system from getting rid of it, as in the case of leishmaniasis. If the Tregs do not work at all due to a mutation, then IPEX syndrome occurs, in which a child dies in the first weeks of life from numerous autoimmune diseases.

These are the same Tregs that parasites use for their own protection, stimulating them through TGFb and interleukin-10. As a result, the Tregs become more active, and suppress the activity of other immune cells, for example, T-helper 2. As a result, it is good for the parasite, since T-helpers 2 cannot effectively develop antiparasitic actions, and it is good for a person, since T-helpers 2 with their excessive activity are one of the main players in allergies.

In parallel, parasites are hedged in another way, reducing the reaction of the humoral link of the immune system: instead of specific and effective IgE class antibodies directed against the helminth, they stimulate the production of less targeted and less effective polyspecific IgE/IgG4 antibodies, a scattering effect is obtained, similar to how one aimed projectile is replaced by pellets flying in a wide fan.

These polyspecific antibodies reduce the effectiveness of mast cells, creating a stupid "noise" effect instead of an aggressive and effective one. And again, it turns out well for both the parasite and the allergic person: after all, the release of a huge number of inflammatory mediator molecules from mast cells is what causes skin itching and rash with allergies, and swelling of the respiratory tract with asthma.

Will we treat?Finally, scientists have the whole set of necessary data: a theory explaining observations in populations with an increase in allergies and autoimmune diseases, animal experiments confirming the theory, a detailed mechanism explaining how it all can work.

At the same time, the number of articles that studied the relationship between helminths and other diseases has already increased.

In particular, it turned out that the "therapeutic" effect is not present in all parasites in a row. For example, data from a meta-analysis of papers on this topic published by Jo Leonardi-Bee et al in 2006 (Am J Respir Crit Care Med Vol 174. pp 514-523, 2006), showed that ascariasis causes not a decrease, but an increase in the incidence of asthma, while hookworm infection leads to a significant and significant decrease in the frequency of asthma, and for other common parasites, the effect is considered unreliable.

It remains to observe the principle of "Do no harm!" so that the positive effect of treatment would still outweigh the possible problems caused by parasites, and try to treat patients with allergies and autoimmune diseases by intentionally infecting with helminths.

1. Vlasoglav (Trichuris suis)JoelWeinstock (Iowa University, USA) and colleagues studied the possibility of treating two autoimmune diseases with this parasite: Crohn's disease and ulcerative colitis.
In ulcerative colitis, 54 patients were divided into 2 groups: experimental, receiving parasite eggs for 2 weeks, and placebo, for 12 weeks. In the main group, a pronounced positive effect was observed in 50% of cases (versus 16% in the placebo group), mainly after 6 weeks. In Crohn's disease, 29 people participated in the study, although without a placebo group, for 24 weeks. A positive effect was observed in 72.4% of cases. At the same time, no problems caused by parasites were observed in both groups. (Summers, R.W. et al., 2005. Trichuris suis therapy in Crohn’s disease. Gut 54, 87-90; Summers, R.W. et al., 2005. Trichuris suis therapy for active ulcerative colitis a randomized controlled trial. Gastroenterology. Apr;128(4):825-32.)

2. Hookworm (N. americanus)22 patients with asthma received injections with hookworm larvae or histamine solution for 16 weeks.
In the group receiving parasites, there was a marked improvement, but the result was unreliable compared to the control group, as a result of which the authors recognized that it was necessary to understand further. However, there were also no problems from the parasite. (Experimental hookworm infection: a randomized placebo-controlled trial in asthma Feary JR at al, Clinical & Experimental Allergy, 40, 299-306.)

What's next?So far, there is too little data to make an unambiguous conclusion about whether we will go to the doctor in the future to get a prescription for packing eggs of some parasite for the treatment of allergies or autoimmune diseases.

And security issues still remain open. For example, worm infestation causes a decrease in the effectiveness of vaccination in children, can worsen the course of tuberculosis and malaria. And in itself, the idea of being treated with parasites is hardly pleasant.

In parallel, alternatives are being studied, for example, the possibility of developing a "helminth vaccine", that is, to isolate from helminths those substances with which they protect themselves and at the same time reduce allergies and treat autoimmune diseases, and still try to avoid treatment in the form of infection by the parasites themselves. Time will show.

One thing is clear already now: there is nothing absolutely and unambiguously unnecessary or absolutely harmful for everyone in nature, getting rid of which will not come back to us later. And medicine in its development often rushes from extreme to extreme: then "extra organs", such as the appendix and tonsils, should be removed by everyone, almost from birth, then hands should be washed 10 times a day with soap...

Portal "Eternal youth" http://vechnayamolodost.ru07.07.2010