Research identifies how inflammatory disease causes fatigue

February 17, 2009,
Image showing a brain blood vessel (outlined in red) and a monocyte within the blood vessel and adherent to the vessel wall (yellow), and a monocyte within the brain after being recruited from the blood (green) in a mouse with liver inflammation. Credit: The Journal of Neuroscience

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 (TNFα). 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.

On the web: www.jneurosci.org/

Source: Society for Neuroscience

Explore further: Brain is susceptible to acute MI, chronic heart failure

Related Stories

Brain is susceptible to acute MI, chronic heart failure

January 17, 2018
(HealthDay)—Acute myocardial infarction (MI) and chronic heart failure have effects on the brain, according to a study published in the Jan. 23 issue of the Journal of the American College of Cardiology.

Dulling cancer therapy's double-edged sword

January 17, 2018
Researchers have discovered that killing cancer cells can actually have the unintended effect of fueling the proliferation of residual, living cancer cells, ultimately leading to aggressive tumor progression.

Memory loss from West Nile virus may be preventable

January 15, 2018
More than 10,000 people in the United States are living with memory loss and other persistent neurological problems that occur after West Nile virus infects the brain.

Inflammation drives progression of Alzheimer's

December 21, 2017
According to a study published in the journal Nature by scientists of the German Center for Neurodegenerative Diseases (DZNE) and the University of Bonn, inflammatory mechanisms caused by the brain's immune system drive the ...

Multiple sclerosis—cholesterol crystals prevent regeneration in central nervous system

January 5, 2018
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, in which the body's own immune cells attack the fatty, insulating myelin sheath surrounding nerve fibers. The regeneration of intact ...

Helpful intestinal bacteria counteracts tendency to depression

December 27, 2017
New research suggests that probiotics, which are active in the intestines, also have an effect on the brain. A study at Aarhus University suggests they protect against depression. In the animal study at the Department of ...

Recommended for you

Onions could hold key to fighting antibiotic resistance

January 22, 2018
A type of onion could help the fight against antibiotic resistance in cases of tuberculosis, a UCL and Birkbeck-led study suggests.

New long-acting approach for malaria therapy developed

January 22, 2018
A new study, published in Nature Communications, conducted by the University of Liverpool and the Johns Hopkins University School of Medicine highlights a new 'long acting' medicine for the prevention of malaria.

Virus shown to be likely cause of mystery polio-like illness

January 22, 2018
A major review by UNSW researchers has identified strong evidence that a virus called Enterovirus D68 is the cause of a mystery polio-like illness that has paralysed children in the US, Canada and Europe.

Study ends debate over role of steroids in treating septic shock

January 19, 2018
The results from the largest ever study of septic shock could improve treatment for critically ill patients and save health systems worldwide hundreds of millions of dollars each year.

New approach could help curtail hospitalizations due to influenza infection

January 18, 2018
More than 700,000 Americans were hospitalized due to illnesses associated with the seasonal flu during the 2014-15 flu season, according to federal estimates. A radical new approach to vaccine development at UCLA may help ...

Flu may be spread just by breathing, new study shows; coughing and sneezing not required

January 18, 2018
It is easier to spread the influenza virus (flu) than previously thought, according to a new University of Maryland-led study released today. People commonly believe that they can catch the flu by exposure to droplets from ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.