Anaphylactic shock or anaphylaxis is a sudden and severe allergic reaction that can be fatal. The reaction involves the whole body; blood pressure and body temperature suddenly drop, which can cause fainting and may cause death. About five percent of people in the United States may suffer anaphylactic shock at some point in their lives due to an allergy to some food, insect bite, or other stimulus. Most of those people have to carry an Epipen in case of accidental exposure; this can relieve anaphylaxis and prevent death by relaxing the muscles that control breathing and stopping the release of reactive allergy molecules in the body. It's been thought that these symptoms are due to a rapid expansion of blood vessels, which may start to leak. But new research using a mouse model has suggested that the nervous system is a crucial player in anaphylaxis. The work has been reported in Science Immunology.
“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., a professor at Duke University School of Medicine.
The sensory nerves that help control body temperature, particularly the nerves that detect high temperatures in the environment, ".. 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.”
Anaphylaxis is caused by allergens in the bloodstream that trigger the widespread activation of IgE-bound perivascular mast cells (MCs). When MCs are activated, they release MC mediators, which are thought to cause many of the symptoms of anaphylaxis like swelling, itchiness, low blood pressure, breathing troubles, and a drop in body temperature.
In this study, the researchers found that when allergens activate mast cells, the molecules that the cells release interact with sensory neurons that are related to the regulation of body temperature. When an allergy stimulates this neural network, the signal shuts down the body-heating mechanism found in brown fat tissue, leading to hypothermia. A sudden drop in blood pressure is also caused by this network.
When the researchers removed an enzyme from perivascular mast cells in the mouse model, the mice no longer experienced hypothermia from allergy. If the heat sensing neurons in the mice were directly activated, however, anaphylactic symptoms like hypothermia and hypotension were still observed.
“By demonstrating that the nervous system is a key player, not just the immune cells, we now have potential targets for prevention or therapy,” said first study author Chunjing “Evangeline” Bao, a graduate candidate in the Abraham lab. “This finding could also be important for other conditions, including septic shock, and we are undertaking those studies.”
Sources: Duke University, Science Immunology
