Researchers from Linköping University in Sweden were able to identify the cells necessary for the appearance of heat in the blood vessels of the brain. The study, conducted on mice and published in the Proceedings of the National Academy of Sciences (PNAS) last October and on the “EurekAlert” website, answered the question: Which organ is responsible for the increase in body temperature?
A fever is a body temperature higher than the normal temperature that varies from person to person, but is usually around 37 degrees Celsius. For the most part, fever is the body’s response to infection and inflammation and the body’s way of defending itself against bacteria and viruses. When the body is exposed to infection or inflammation, it responds by releasing molecules called cytokines into the bloodstream, and these molecules are too large to cross the blood-brain barrier, a network of capillaries that protect the brain from substances that can cause harm.
The outer surface of the blood-brain barrier contains receptors that recognize cytokines, and these receptors transmit the signal to cells on the inner surface of the blood vessel walls in the blood-brain barrier, known as endothelial cells, and then begin to produce a molecule similar to the hormone prostaglandin which in turn activates receptors in the hypothalamus area, which regulate the body temperature, and induce heat. However, it is still unclear whether this is the only mechanism behind the heat.
In the past, it was thought that prostaglandins must also be produced in certain cells of certain organs such as the liver and lungs to initiate the heat response, but researchers from Linköping University have shown that this is not the case, as it turns out that only the endothelial cells of the brain are required to produce the heat response. “Our results answer a question that has been asked for decades. There has never been any evidence that only brain endothelial cells are necessary to initiate a heat response,” says Anders Blomqvist, professor at Linköping University.
The researchers worked with genetically modified mice, removing some of the genes that code for the production of prostaglandins in the endothelial cells of the brain. Then they injected the mice with substances found in the cell walls of certain bacteria, which produced heat in this way. The genetically modified mice showed no response to heat after the injection.
This allowed the researchers to conclude that these endothelial cells are necessary to cause fever, but it is not seen whether they are sufficient. For this reason, the researchers tested another genetically modified mouse model in which the only cells that could produce prostaglandin E2 were the endothelial cells of the brain. These mice showed a heat response, confirming that the endothelial cells in the brain are already sufficient.