A key feature of a severe allergic reaction known as anaphylaxis is a sudden drop in blood pressure and body temperature, leading to unconsciousness and, if untreated, potential death.
This reaction has long been attributed to the sudden dilation and leakage of blood vessels. But in a study of mice, Duke Health researchers found that this response, particularly the lowering of body temperature, requires an additional mechanism — the nervous system.
Will appear online on March 17 in the magazine The science of immunologythe study may point to new targets for therapy to prevent or treat anaphylactic shock, which occurs in up to 5% of people in the US each year in response to food allergies or insect or venomous animal bites.
“This finding for the first time identifies the nervous system as a key player in the anaphylactic reaction,” said senior author Soman Abraham, Ph.D., professor in the Departments of Pathology, Immunology, and Molecular Genetics and Microbiology at Duke University. medicine.
“Sensory nerves involved in thermal regulation — especially nerves that sense high ambient temperatures — send a false signal to the brain during anaphylaxis that the body is being exposed to high temperatures, even though it’s not,” Abraham said. “This causes a rapid drop in body temperature as well as blood pressure.”
Abraham and colleagues, including first author Chongjing “Evangeline” Bao, Ph.D. candidate in Abraham’s lab at Duke tracked 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 discovered 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 is signaled to immediately turn off the heat generators in the brown adipose tissue, causing hypothermia. Activation of this network also causes a sudden drop in blood pressure.
The researchers confirmed their findings by showing that depriving mice of a specific mast cell enzyme protected them from hypothermia, while direct activation of heat-sensing neurons in mice caused 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 therapy,” Bao said. “This discovery may also be important for other diseases, including septic shock, and we are conducting these studies.”
In addition to Bao and Abraham, the study’s authors include Yuan Chen, Huaxing Shen, 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).