Key Role Identified for Nervous System in Severe Allergic Shock

A key feature of the severe allergic reaction known as anaphylaxis is an abrupt drop in blood pressure and body temperature, causing people to faint and, if untreated, potentially die.

That response has long been attributed to a sudden dilation and leakage of blood vessels. But Duke Health researchers have found that this response, especially body temperature drop, requires an additional mechanism, the nervous system.

“This finding for the first time identifies the nervous system as a key player in the anaphylactic response,” said senior author Soman Abraham, Ph.D.

“The sensory nerves involved in thermoregulation send the brain a false signal during anaphylaxis that the body is exposed to high temperatures even though it is not the case,” Abraham said. “This causes a rapid drop in body temperature as well as blood pressure.”

Abraham and colleagues tracked the sequence of events when allergens activate mast cells (the immune cells that trigger the chemical reactions leading to swelling, difficulty breathing, itchiness, low blood pressure and hypothermia).

The researchers found that one of the chemicals mast cells unleash when they are activated is an enzyme that interacts with sensory neurons, notably those involved in the body’s thermoregulatory neural network.

When stimulated as part of an allergic reaction, this neural network gets the signal to immediately shut down the body’s heat generators in the brown fat tissue, causing hypothermia. The activation of this network also causes a sudden drop in blood pressure.

The researchers validated their findings by showing that depriving mice of the specific mast cell enzyme protected them against hypothermia, whereas directly activating the heat sensing neurons in mice induced anaphylactic reactions such as hypothermia and hypotension.

“By demonstrating that the nervous system is a key player, not just the immune cells, we now have potential targets for prevention or therapy,” Bao said. “This finding could also be important for other conditions, including septic shock, and we are undertaking those studies.”


Chunjing Bao, Ouyang Chen, Huaxin Sheng, Jeffrey Zhang, Yikai Luo, Byron W. Hayes, Han Liang, Wolfgang Liedtke, Ru-Rong Ji, Soman N. Abraham. A mast cell–thermoregulatory neuron circuit axis regulates hypothermia in anaphylaxis. Science Immunology, 2023; 8 (81) DOI: 10.1126/sciimmunol.adc9417

Duke University Medical Center. “Key role identified for nervous system in severe allergic shock: Anaphylaxis reactions linked to the body’s temperature control mechanisms in the central nervous system.” ScienceDaily. ScienceDaily, 17 March 2023. <>.

Images from:

Photo by Pixelumina Photography