A sudden drop in blood pressure and body temperature is a key feature of the severe allergic reaction known as anaphylaxis, which causes people to faint and potentially die if left untreated. This response has long been attributed to dilation and leakage of blood vessels. However, researchers at Duke Health discovered in a mouse study that this response, specifically the drop in body temperature, requires an additional mechanism – the nervous system.
The study’s findings, published in the journal Science Immunology, could point to new targets for therapies to prevent or treat anaphylactic shock, which occurs in up to 5 percent of people in the United States annually in response to food allergies or bites from insects or venomous animals.
“This finding identifies for the first time the nervous system as a key player in the anaphylactic response,” said senior author Soman Abraham, Ph.D., professor in the Departments of Pathology, Immunology and Molecular Genetics and Microbiology at Duke University School of Medicine. “The sensory nerves involved in thermoregulation — particularly the nerves that sense high ambient temperatures — send a false signal to the brain during anaphylaxis that the body is experiencing high temperatures, when it isn’t,” Abraham said .
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“This causes a rapid drop in body temperature and blood pressure.” Abraham and colleagues, including first author Chunjing “Evangeline” Bao, a Ph.D. Candidate in Abraham’s lab at Duke, followed the sequence of events when allergens activate mast cells — the immune cells that trigger the chemical reactions that lead to swelling, difficulty breathing, itching, low blood pressure and hypothermia.
The researchers found that one of the chemicals that mast cells release when they are activated is an enzyme that interacts with sensory neurons, particularly those involved in the body’s thermoregulatory neural network. When stimulated as part of an allergic reaction, this neural network receives the signal to immediately turn off the body’s own heat generators in brown adipose tissue, resulting in hypothermia.
Activation of this network also causes a sudden drop in blood pressure. The researchers validated their results by showing that deprivation of the specific mast cell enzyme protected mice from hypothermia, while direct activation of the heat-sensitive neurons in mice elicited anaphylactic reactions such as hypothermia and hypotension.
“By demonstrating that the nervous system plays a key role — not just the immune cells — we now have potential targets for prevention or therapy,” Bao said. “This finding could be important for other conditions as well, including septic shock, and we’re conducting these studies.”
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