Researchers identify cells in the brain’s blood vessels involved in creating a fever

Researchers at Linköping University have identified in mice the cells in the blood vessels of the brain that are essential for the fever response. The results were published in Proceedings of the National Academy of Sciences (PNAS), and answers a longstanding question about which organs are involved in fever production.

“Everybody has a fever from time to time. If we understand the mechanism behind feverAnders Blomqvist, professor emeritus at the Department of Biomedical and Clinical Sciences, Linköping University.

Fever is the body’s response to infection or inflammation and is a defense mechanism against viruses and bacteria, for example. When affected by infection or inflammation, the body releases molecules called cytokines into the body blood cycle. These molecules are too big to pass through the blood-Brain barrier, a network of small blood vessels that helps protect the brain from Harmful Substances. But fever is just a symptom, manifesting after the brain sends out a signal on its own. So how does the brain detect that the body is affected by inflammation or infection?

The explanation can be found in receptors located on the outer surface of the blood-brain barrier that detect cytokines. These receptors transmit signals to cell on the inner surface of the internal blood vessel wall cerebral blood vessel blockageknown as endothelial cells. They then start producing the hormone prostaglandin E2-like molecule, which in turn activates receptors in the hypothalamus, which act as the body’s thermostat. A febrile reaction has been initiated. However, it was previously unclear whether this was the sole mechanism behind the fever.

It was previously believed that prostaglandins must also be produced in certain cells of organs such as the liver and lungs to initiate a fever response. But researchers at Linköping University have shown that’s not the case. In a study on mouse published year PNASAnders Blomqvist and his colleagues show that the endothelial cells of the brain are the only cells needed to induce a fever response.

“Our results answer a question that has been asked for decades. There hasn’t been any evidence before that only endothelial cells in the brain are needed to initiate a response,” Anders said. We’ve filled this gap in our knowledge.” Blomqvist.

The researchers worked with gene-edited mice, in which they removed certain genes that code for prostaglandin production in brain endothelial cells. The mice were then injected with substances found in the cell walls of certain bacteria, which induce fever in this way. The gene-edited mice did not have any febrile response after injection.

This allowed the researchers to conclude that these endothelial cells were necessary for fever, but did not show whether they were sufficient. For this reason, the researchers tested another gene-edited mouse model in which the only cells able to produce prostaglandin E2 were brain endothelial cells. These mice exhibited a febrile response, which confirms that brain endothelial cells are indeed sufficient.

These experiments were made possible thanks to advanced techniques for managing and testing laboratory animals. By surgically inserting an intravenous catheter and recording the body temperature with a telemeter, both the injection and the measurement can be performed without stress to the animal, which means that a febrile reaction can occur. observed more precisely.

“The public has long believed that the body temperature of small animals is higher than that of humans and other animals. large mammalsabout 40 degrees [Celsius]. But the measurements were wrong, as the animals became stressed in the process. “The techniques we used showed that the mice had temperatures comparable to those of humans,” says Anders Blomqvist.