The blood vessels in the brain are the only crucial link in the development of fever. The endothelial cells in the wall of the blood vessels play an important role in transmitting the inflammatory signal to the brain. Researchers from Linköping University in Sweden write this in the scientific journal PNAS.
Signaling molecules
When viruses or bacteria enter the body, the immune system sounds the alarm. Large amounts of signaling molecules, the so-called cytokines, are then released into the bloodstream in a chain reaction against the invaders. These signaling substances are known to trigger fever, but they themselves are too large to cross the blood-brain barrier. Since the “thermostat” that regulates body temperature is located deep in the brain in the hypothalamus, the inflammatory signal has to get there in a different way.
Scientists have long suspected that the signal travels to the brain via prostagladin-producing cells. Prostaglandin E2 is a hormone-like molecule that binds to receptors in the hypothalamus. Furthermore, it is known that endothelial cells in the blood vessels start to produce prostaglandin in response to cyokines. They do this not only in the brain, but also, for example, in the lungs and liver. The question of how exactly the signal reaches the brain therefore remained open.
The Swedish researchers have now finally solved the puzzle with advanced experiments with mice. They have now conclusively shown that only the endothelial cells in the blood vessels of the brain transmit the inflammatory stimulus to the brain.
In the experiments, they worked with two different groups of genetically modified mice. The first group of mice could not produce prostaglandin in the endothelial cells of the brain and did not develop a fever in the experiment. The second group of mice could only produce prostaglandin with the brain’s endothelial cells and did develop a fever.
Kathether
The researchers used a remote-controlled catheter so that they could administer a dose of bacterial proteins to the mice “unnoticed.” This makes the temperature measurements more accurate, because the animals are not stressed by animal handling.
Karin Mulders-Manders, internist at Radboudumc in Nijmegen, says that this thorough approach makes the study special. For the experiments, the scientists not only switched off proteins, as had been done before, but switched specific proteins in the brain on and off. “Until now, we didn’t know that the blood vessels of the brain were so important,” says Mulders-Manders. “We thought the lungs and liver could also contribute. But they are not as important as we thought.”
Mouse studies do not always say everything about how processes in the human body work. But because the exact same molecules also play the same role in fever in humans, you can assume that the blood vessels in the brain also play a key role in humans,” says Mulders-Manders.