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Researchers pinpoint fever center in brain
CHICAGO (Reuters) - A tiny spot in the brain triggers fever in mice, U.S. researchers said on Sunday, and understanding how it works may lead to more specific drugs to control fever and other ills in humans.
When people get sick, white blood cells send chemical signals called cytokines to marshal defenses in the body. These messengers tell blood vessels in the brain to make a second hormone, prostaglandin E2.
"This triggers the brain responses during an infection or inflammation," said Dr. Clifford Saper of Harvard Medical School's Beth Israel Deaconess Medical Center in Boston, whose study appears in the journal Nature Neuroscience.
Researchers knew that prostaglandin E2 acted on the hypothalamus, an area of the brain that controls basic functions like eating, drinking, sex and body temperature.
Saper and colleagues wanted to find which nerve cells in the brain generate fever. To do that, they used special laboratory mice and systematically eliminated genes for specific EP3 receptors -- a part of the brain that picks up on the prostaglandin E2 hormone.
Many cells in the brain make EP3 receptors, which Saper thinks may trigger other symptoms such as fatigue, loss of appetite, and fatigue associated with infection.
"What we found is if you take the EP3 receptor out of this one site that is about the size of the head of a pin, you no longer get a fever response," he said in a telephone interview.
"We expect this is exactly what is going on in the human brain as well."
Current pain killers like aspirin act on all prostaglandin receptors in the body, but they have lots of other effects as well, Saper said.
Knowing how to find and eliminate receptors linked with fever may help with the development of highly specific drugs that act on a specific receptor, he said.
It may also lead to drugs to prevent loss of appetite or fatigue associated with infections.
"Ultimately, you may be able to manipulate those circuits with drugs," he said. "The trick is you need to know which circuits were involved in each of these things."
