Severe allergic shock, also known as anaphylaxis, is a life-threatening condition that can occur in response to an allergen such as food, medication, or insect venom. While the immune system is known to play a central role in anaphylaxis, recent research has identified a key role for the nervous system in this condition.
An abrupt drop in blood pressure and body temperature is a key feature of the severe allergic reaction known as anaphylaxis, causing people to faint and, if untreated, potentially die. That response has long been attributed to blood vessel dilation and leakage. However, in a mouse study, Duke Health researchers discovered that this response, particularly body temperature drop, requires an additional mechanism – the nervous system.
The study, published online in the journal Science Immunology, could point to new targets for therapies to prevent or treat anaphylactic shock, which affects up to 5% of people in the United States each year as a result of food allergies or bites from insects or venomous animals.
This finding identifies the nervous system as a key player in the anaphylactic response for the first time. During anaphylaxis, the sensory nerves involved in thermal regulation, particularly the nerves that sense high environmental temperatures, send the brain a false signal that the body is exposed to high temperatures, which is not the case.
Soman Abraham
“This finding identifies the nervous system as a key player in the anaphylactic response for the first time,” said senior author Soman Abraham, Ph.D., professor of Pathology, Immunology, Molecular Genetics, and Microbiology at Duke University School of Medicine.
“During anaphylaxis, the sensory nerves involved in thermal regulation, particularly the nerves that sense high environmental temperatures, send the brain a false signal that the body is exposed to high temperatures, which is not the case,” Abraham explained. “This results in 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, 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 discovered that one of the chemicals released by mast cells when activated is an enzyme that interacts with sensory neurons, particularly those in the body’s thermoregulatory neural network.
When this neural network is stimulated as part of an allergic reaction, it receives the signal to immediately shut down the body’s heat generators in the brown fat tissue, resulting in hypothermia. When this network is activated, blood pressure drops dramatically.
The researchers validated their findings by demonstrating that deprivation of a specific mast cell enzyme protected mice from hypothermia, whereas directly activating heat-sensing neurons in mice caused anaphylactic reactions such as hypothermia and hypotension.
“By demonstrating that the nervous system, not just immune cells, is a key player, we now have potential targets for prevention or therapy,” Bao said. “This finding could be important for other conditions, such as septic shock, and we are conducting additional research.”
