Researchers have described the mechanism of formation for a key substance that triggers fever. Image: Flickr

Occasionally we’re hit by fever. Nobody likes it, most sane people actually hate it, but it’s important to note that it’s an important part of the healing process. Fever is a result of the immune response by your body to foreign invaders like viruses, bacteria, fungi, drugs, or other toxins. Research showed that it is triggered by an onset of the signaling substance prostaglandin. For some time, researchers have been debating where this signal originates, but new developments at the Linköping University in Sweden have finally settled the matter: prostaglandin originates in the brain. This key insight could pave way for a new class of drugs that suppress certain fever symptoms, but keep the ones that are essential to healing.

From the brain to the rest of the body

Aspirin is great for fever and researchers should it works its magic by suppressing prostaglandins producing throughout the body. Thus all inflammation symptoms are eased simultaneously: fever, pain, loss of appetite and so on. In some cases though, it might not be desirable to get rid of all these symptoms. After all, the body’s responses to invaders isn’t there for nothing – it fits a purpose.

”Perhaps you want to inhibit loss of appetite but retain fever. In the case of serious infections, fever can be a good thing,” says David Engblom, senior lecturer in neurobiology at Linköping University.

Actually, Engblom discovered the mechanism behind the formation of prostaglandin E2 during fever some eleven years ago. He found the signaling molecules are unable to pass the blood-brain barrier, which protects the brain from hazardous substances. What he found instead is that prostaglandin can be synthesized from two enzymes in the blood vessels inside the brain, before reaching the hypothalamus where the body’s thermostat is located.

Many years later, Engblom and colleagues finally confirmed their theory was correct. The researchers made tests on mice that lack the enzymes COX-2 and mPGES-1 in the brain’s blood vessels. When they were infected with bacterial toxins the fever did not appear, while other signs of inflammation were not affected, proving that the hypothesized mechanism is correct.

”This shows that those prostaglandins which cause fever are formed in the blood-brain barrier – nowhere else. Now it will be interesting to investigate the other inflammation symptoms. Knowledge of this type can be useful when developing drugs that ease certain symptoms, but not all of them,” explains David Engblom.