Flipping Off Inflammation

'Master switch' influences inflammation in autoimmune diseases like rheumatoid arthritis, multiple sclerosis

(RxWiki News) A "master switch" protein in white blood cells has been found to influence whether the cells promote or hinder inflammation, according to a new study.

The finding could help lead researchers to new treatments for inflammatory diseases such as rheumatoid arthritis.

Inflammation is an important defense against harmful stimuli such as infections or tissue damage, but excessive inflammation in diseases like rheumatoid arthritis causes damage. In the case of rheumatoid arthritis, joints become swollen and painful.

Results from the new study confirm a protein known as IRF5 acts as a molecular switch that controls white blood cells known as macrophages that can cause or inhibit inflammation. Boosting IRF5 levels in macrophages may help treat those with compromised immune systems, such as HIV patients, whereas blocking the production of IRF5 in macrophages may open the door to more effective treatments for autoimmune diseases like RA, inflammatory bowel disease, lupus and multiple sclerosis.

Researchers at Imperial College London had perviously developed anti-TNF treatments, which target TNF signaling chemicals released by immune cells to stimulate inflammatory responses in RA and other diseases. Anti-TNF treatments inhibit the cytokine tumor necrosis factor (TNF). TNF can cause inflammation that results in chronic conditions.

Since this treatment doesn't work in about 30 percent of patients, researchers at the Kennedy Institute of Rheumatology at Imperial College London wanted to better understand how genes are switched on and off in certain cells, which is "crucial for designing targeted strategies to suppress unwanted cell responses," said senior investigator Dr Irina Udalova.

The researchers used engineered viruses to introduce more copies of the IRF5 gene in human, laboratory-grown macrophages. When IRF5 was inhibited in pro-inflammatory macrophages with synthetic molecules, a reduction in the cells' production of signals that promote inflammation occurred.

Results from the study indicate IRF5 acts as the master switch in this key set of immune cells, which is exciting, according to researchers since it could lead to new anti-inflammatory treatments for a wide variety of conditions.

Review Date: 
January 17, 2011