30 April 2020

Medicine from parasites

Larvae of intestinal worms suppressed inflammation in allergies and asthma

Alice Bakhareva, N+1

The extract of parasitic nematode larvae has an anti-inflammatory effect in immune reactions of the second type, which are the basis of allergies and asthma. The active substance of the larvae – the enzyme glutamate dehydrogenase – reduces the release of pro-inflammatory eicosanoids in human macrophages, suppresses the migration of granulocytes to the focus of inflammation and stops allergic reactions in mice, according to an article published in the journal Science Translational Medicine (Marta de los Reyes Jiménez et al., An anti-inflammatory eicosanoid switch mediates the suppression of type-2 inflammation by helminth larval products).

Parasitic worms cause protective immune reactions in the host organism. In order to survive, helminths suppress the host's immunity: they have mechanisms for inhibiting inflammatory processes, including inflammation of the second type, which causes bronchial asthma and allergic reactions. For example, intestinal parasites of rodents Heligmosomoides polygyrus bakeri secrete substances that suppress allergic inflammation of the respiratory tract in mice.

Scientists from Germany, Switzerland and Sweden, led by Julia Esser-von Bieren from the Technical University of Munich, investigated the effect of substances of nematode larvae Heligmosomoides polygyrus bakeri for inflammation of the second type. Allergic reactions to dust mites were caused in mice and extract of nematode larvae was injected intranasally. The extract was also added to the culture of human macrophages, in which the release of eicosanoids was artificially induced. These substances are the key factors of inflammatory processes of the second type.

In addition, the effect of nematode larval extract on the involvement of granulocytes (a subtype of leukocytes) in inflammation in aspirin asthma was tested. Nasal polyps and leukocytes were collected from six patients with this disease. They were grown in culture and observed the migration of granulocytes to polyps in the presence of an extract of worm larvae.

The extract of nematode larvae reduced the symptoms of respiratory tract allergy and the number of markers of inflammation in the lungs (p<0.05). In macrophages to which the extract was added, the profile of eicosanoid release shifted from pro-inflammatory factors to regulatory ones. Chemotaxis of granulocytes to nasal polyps of patients with aspirin asthma significantly decreased (p<0.01).

To determine which substances help nematode larvae regulate inflammation of the second type, separate protein fractions were isolated from the extract using gel-penetrating chromatography. Their effect was evaluated by their ability to inhibit proinflammatory ecicosanoids.

The active substance was the enzyme glutamate dehydrogenase. When it was blocked with a specific inhibitor bithionol (it is used as an anthelmintic drug) or antibodies, it stopped changing the profile of eicosanoids in macrophages. The researchers created recombinant glutamate dehydrogenase and added it to macrophage culture or injected intranasally into mice with allergic reactions. In both cases, the enzyme effectively suppressed the inflammatory process (p<0.05).

Parasitic worms are not the only animals that are associated with allergy suppression. Children who grow up in a house with pets are less likely to have allergies to wool and pollen. The more pets there are, the less likely it is to develop allergies. Not only animals, but also bacteria can help protect against allergies – if they live in the intestines of a pregnant woman.

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