A key feature of a severe allergic reaction known as anaphylaxis is a sudden drop in blood pressure and body temperature, leading to fainting, and possibly death if not treated.
This response has long been attributed to sudden dilation and leakage of blood vessels. But in a study of mice, Duke Health researchers found that this response, particularly hypothermia, requires an additional mechanism — the nervous system.
Appearing online March 17 in the magazine ImmunologyThe study could indicate new targets for therapies to prevent or treat anaphylactic shock, which occurs in up to 5% of people in the United States annually in response to food allergies or bites from poisonous insects or animals.
“This finding identifies for the first time the nervous system as a key player in the anaphylactic response,” said lead author Suman Abraham, PhD, professor in the departments of Pathology, Immunology, and Molecular Genetics and Microbiology at Duke University. from medicine.
“The sensory nerves involved in thermoregulation – particularly the nerves that sense high environmental temperatures – send the wrong signal to the brain during anaphylaxis that the body is exposed to high temperatures even though that is not the case,” Abraham said. This causes a rapid drop in body temperature and blood pressure.
Abraham and colleagues, including first author Zhongying “Evangeline” Bao, Ph.D. Candidate in Abraham’s lab at Duke, she traces the sequence of events when allergens activate mast cells—immune cells that trigger chemical reactions that lead to swelling, difficulty breathing, itching, low blood pressure, and hypothermia.
The researchers found that one of the chemicals released by mast cells when activated is an enzyme that interacts with sensory neurons, particularly those involved in the body’s temperature-regulating neural network.
When stimulated as part of an allergic reaction, this neural network gets a signal to immediately turn off the body’s thermogenerators in brown adipose tissue, causing hypothermia. Activation of this network also leads to a sudden drop in blood pressure.
The researchers validated their findings by showing that depriving mice of a specific mast cell enzyme protects them from hypothermia, while direct activation of heat-sensing neurons in mice causes anaphylactic reactions such as hypothermia and hypotension.
“By demonstrating that the nervous system is a key player — not just immune cells — we now have potential targets for prevention or treatment,” said Bao. “This finding could also be important for other conditions, including septic shock, and we are conducting those studies.”
In addition to Bao and Abraham, study authors include Ouyang Chen, Huaxin Sheng, Jeffrey Zhang, Yikai Luo, Byron W. Hayes, Han Liang, Wolfgang Liedtke, and Ru-Rong Ji.
The study received funding from the National Institutes of Health (R01-GM144606).
