The nervous system can affect severe allergic reactions | Science

Peanuts have a dark side. In some people, they can cause a dangerous and sometimes fatal allergic reaction, characterized by a sharp drop in body temperature and blood pressure, as well as difficulty breathing. This anaphylactic shock is typically blamed on the immune system going into overdrive. But a new study in mice pinpoints an additional culprit: the nervous system.

The findings reported today Science Immunology, “correspond to what people thought but no one could actually demonstrate,” says Sebastien Talbot, a neuroimmunologist at Queen’s University who was not involved in the study. He says the work could open up new targets for treating severe allergic reactions in humans.

Anaphylaxis affects about one in fifty people in the United States each year. In addition to peanuts, bee stings and some medications are common triggers. These allergens cause immune system mast cells to release histamine and other molecules that spread throughout the body, dilating blood vessels and constricting airways. Body temperature can also drop, making people feel cold and clammy, but why this happens has not been as clear.

Mice also have anaphylaxis. When exposed to an allergen, they lie on their stomachs and stretch. Such behavior is controlled by the central nervous system, leading Duke University immunologist Soman Abraham to suspect that nerves may also play a role in severe allergic reactions.

To find out, he and colleagues gave mice ovalbumin — the main protein found in egg whites and a known anaphylaxis trigger — and used electrodes and microscopy to record and measure nerve cell activity. Like humans, the body temperature of the rodents decreased – about 10 °C. But the mice’s brains didn’t register this as a sudden freeze; instead, brain regions that typically respond to heat had higher activity. This false sense of warmth explains why animals stretch as if they are overheated, even when their body temperature drops.

But what tells mice that they are overheating? The researchers found neurons in the spinal cord that appeared to be particularly active during anaphylaxis. When the team manipulated the neurons’ receptors to effectively shut them down, the animals did not cool down during anaphylaxis. On the other hand, activating the neurons recreated the symptoms of anaphylaxis even without allergen exposure.

During actual anaphylaxis, mast cells appear to be key to this phenomenon. The team found that in addition to histamines, the cells release a compound called chymase, which interacts with neurons associated with brain regions that regulate body temperature. When the group blocked the release of chymase, the animals no longer lowered their body temperature in response to the allergen.

Immunologists have long believed that histamine is a major factor in anaphylaxis, Talbot says, so it was surprising to him that the brain—and the nervous system—also seems to play a role. “It was cool to find a new mediator that actually triggered crosstalk between neurons and neurons [immune] cells.”

The research could provide new targets for the treatment of anaphylaxis in humans. People with severe allergic reactions often have to carry an EpiPen, which delivers adrenaline to stop the reaction once it starts. But preventive treatments have been lacking.

Drugs that block communication between immune cells and neurons by targeting chymase or the receptors it activates on neurons may be a way to help people who suffer from severe allergic reactions, says Evangeline Bao, a Duke immunologist and co-author of the study. new research. Because these would target the root cause of the reaction, rather than just relieve the symptoms, as the EpiPen does, this might be a better strategy — and more preventative, he says.

Immune and nervous system crosstalk can also play a role in other serious reactions, Bao says. He and his colleagues are now studying how this communication works in sepsis, the body’s overreaction to infection. Like anaphylaxis, sepsis is an overreaction to an insult; in this case, immune cells release inflammatory molecules that can damage organs and in some cases lead to death.

Such applications are still a long way off, Talbot warns. Still, he says, “The study is sure to spark a lot of research in the field.”

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