RESEARCHERS IDENTIFY BRAIN CELLS RESPONSIBLE FOR FEVER
Written by: Joe Gelb, Clinical Publicist, HPS Pharmacies
A report published on 12 August 2007 in the journal Nature Neuroscience describes the discovery by a team of researchers at Beth Israel Deaconess Medical Centre in Boston, led by Dr Clifford B Saper, a neurologist and neuroscientist whose laboratory conducted the research, of the precise brain cells that cause the body’s temperature to rise in response to inflammation.
While fever, aches and pains, loss of appetite and lethargy “may seem uncomfortable at the time”, Dr Saper noted, “they are part of an adaptive response, coordinated by the hypothalamus, to help survive an infection. If you raise the body’s temperature a few degrees, white blood cells become more active; they actually fight harder. But most bacteria don’t grow as well” - that being the reason that fever can help the body overcome a bacterial infection.
Dr Saper described his work as being part of an effort to “dissect molecularly what is going on in the brain when you have this response.”
Fever occurs in response to inflammation, which can accompany bacterial infections, some viral infections and some non-infectious conditions such as arthritis and Crohn’s disease. In response to these morbidities, the body releases prostaglandins, hormones which cross into the brain and are responsible for fever and the other symptoms.
This can be clearly demonstrated by the fever-reducing action of aspirin and non-steroidal anti-inflammatory drugs, which act by preventing the formation of prostaglandins, thus reducing or eliminating inflammation and its consequences.
Researchers discovered that prostaglandins bind to a specific kind of receptor, EP3, to cause fever. They also found that this binding occurs in the brain’s hypothalamus, an area that coordinates basic activities related to survival, such as hunger and sex drive.
While knowing that the prostaglandins acted on EP3 receptors somewhere in the hypothalamus, the exact location of several possible sites where the binding could occur remained unresolved.
In the current research, Dr Saper’s team identified the precise location by creating a mouse model in which the gene for the EP3 receptor in the brain could be switched off at a single minuscule site at a time.
The process used by Dr Saper and his team was described by a leading expert on fever, Dr Andrej A Romanovsky, director of the systemic inflammation laboratory at St Joseph’s Hospital in Phoenix, Arizona, as “very new” and “very sexy”, and that the new findings were “convincing and important.”
The site identified by Dr Saper’s team is located in the part of the hypothalamus called the median preoptic nucleus, just behind the eyes, where the optic nerves cross paths as they enter the brain. The team demonstrated that when the gene for the right prostaglandin receptor was deleted from the specific cells, the mice no longer developed fever.
Dr Saper commented that in the long run such molecular details could prove useful to drug development. “It may be possible to block specific prostaglandin receptors that are responsible only for fever, or only for achiness or lethargy or loss of appetite,” he stated. For instance, “maybe in a bacterial infection you want the fever, but you don’t want to feel achy and crummy. Or maybe with non-infectious diseases like arthritis or Crohn’s disease, where the fever isn’t adaptive, you want to block the fever as well.”
“We are looking at this research as a key that will open a number of locks in the brain, to tell us how some of these systems in the brain work and what we can do about that.” Dr Saper concluded
Reference: Nature Neuroscience; 12 August 2007