Adaptive source of fever identified

 

US scientists have found that a fever is produced by the behaviour of a hormone on a specific site in the brain.

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This answers a key question as to how this adaptive function helps protect the body during bacterial infection and other types of illness.

“This study shows how the brain produces fever responses during infections,” wrote senior author Clifford Saper, MD, PhD, Chairman of the Department of Neurology at BIDMC and James Jackson Putnam Professor of Neurology and Neuroscience at Harvard Medical School.

“Our laboratory identified the key site in the brain at which a hormone called prostaglandin E2 (PGE2) acts on a target, called the EP3 receptor, on neurons to cause the fever response.”

During periods of inflammation, such as when the body is fighting an infection or illness, the body produces hormones known as cytokines.

The cytokines, in turn, act on blood vessels in the brain to produce PGE2.

Illness as adaptive response

“PGE2 then enters the brain’s hypothalamus, causing fever, loss of appetite, fatigue and general feelings of sickness and achiness,” said Saper, explaining that these common symptoms of illness function as an adaptive response to enable the body to better fight infection.

“When body temperature is elevated by a few degrees, white blood cells can fight infections more effectively. Also, individuals tend to become achy and lethargic.

“Consequently, they tend to take it easy, thereby conserving their energy so that they can better fight the infection. That is why so many different types of illness result in more or less the same sickness behaviours,” he added.

To this point, the specific neurons on which PGE2 was acting to produce fever were unknown.

The team used a mouse in which the gene for the EP3 receptor, which registers the presence of PGE2, could be removed in one part of the brain at a time.

“This was the first time that anyone has been able to remove the receptor at a single spot in the brain,” said Saper.

“As a result, we are able to definitively say that this particular site in the brain – only a little bigger than the head of a pin – is where prostaglandins work to cause the fever response.

The study was reported by researchers at Beth Israel Deaconess Medical Center (BIDMC). The study results appear in Nature Neuroscience’s Advance Online Publication.

“We think that the other aspects of sickness behaviour, such as the achiness caused by increased sensitivity to pain, also come from specific sites in the brain,” he explained.

“We plan to use this same approach to dissect the brain’s response to inflammation, and find out why people feel the way they do when they are ill.”

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