http://www.sciencedaily.com/ releases/ 2009/02/09021717 3034.htm

How Inflammatory Disease Causes Fatigue

ScienceDaily (Feb. 28, 2009) - New animal research in the February 18 issue of
The Journal of Neuroscience may indicate how certain diseases make people feel
so tired and listless. Although the brain is usually isolated from the immune
system, the study suggests that certain behavioral changes suffered by those
with chronic inflammatory diseases are caused by the infiltration of immune
cells into the brain. The findings suggest possible new treatment avenues to
improve patients' quality of life.

Chronic inflammatory diseases like rheumatoid arthritis, inflammatory bowel
disease, psoriasis, and liver disease cause "sickness behaviors," including
fatigue, malaise, and loss of social interest. However, it has been unclear how
inflammation in other organs in the body can impact the brain and behavior.
The researchers found that in mice with inflamed livers, white blood cells
called monocytes infiltrated the brain. These findings support previous research
demonstrating the presence of immune cells in the brain following organ
inflammation, challenging the long-held belief that the blood-brain barrier
prevents immune cells from accessing the brain.
"Using an experimental model of liver inflammation, our group has demonstrated
for the first time the existence of a novel communication pathway between the
inflamed liver and the brain," said the study's senior author Mark Swain, MD,
Professor of Medicine at the University of Calgary.
Swain and his colleagues found that liver inflammation triggered brain cells
called microglia to produce CCL2, a chemical that attracts monocytes. When the
researchers blocked CCL2 signaling, monocytes did not enter the brain despite
ongoing inflammation in the liver.
Liver inflammation also stimulated cells in the blood to make an immune chemical
(TNFá). When the researchers blocked the signaling of this immune chemical,
microglia produced less CCL2, and monocytes stayed out of the brain.
In the mice with inflamed livers, preventing the entry of monocytes into the
brain reduced sickness behaviors; mice showed more mobility and social
interaction. These findings suggest that people with chronic inflammatory
diseases may benefit from treatments that limit monocyte access to the brain.
"Sickness behavior significantly impacts quality of life. Our findings further
our understanding and may generate potential new avenues for treatment of these
often crippling symptoms," said Swain.
"The brain is the master coordinator of many of our bodies' defense responses,
so it must be able to sense injury and inflammation in distant body organs. This
study starts to explain the peripheral communication signals that activate the
brain," said Nancy Rothwell, PhD, DSc, at the University of Manchester, an
expert on brain inflammation who is unaffiliated with the study.
The research was supported by the Canadian Institutes of Health Research, the
Canadian Liver Foundation, and the Alberta Heritage Foundation for Medical
Research.

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Adapted from materials provided by Society for Neuroscience, via EurekAlert!, a
service of AAAS.

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