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‘Master Switch’ Found For Inflammatory Diseases

January 17, 2011

Scientists have discovered a protein that acts like a “master switch” determining whether white blood cells will boost or dampen inflammation, a discovery that could help researchers find new drugs, or possibly even a cure, for rheumatoid arthritis.

Many patients with rheumatoid arthritis are treated with a class of medications called tumor necrosis factor (TNF) inhibitors made by a number of drug companies including Abbott Laboratories, Merck, Pfizer and Amgen.

But as many as 30 percent of those patients do not respond well to anti-TNF drugs, so experts say it is imperative to develop more widely effective treatment options for the debilitating condition.

In the study, published in the journal Nature Immunology on Sunday, scientists from Imperial College London found that the protein IRF5 acts as a molecular switch that controls whether white blood cells — known as macrophages — will promote or inhibit inflammation.

The scientists said the results suggest that blocking the production of IRF5 in macrophages could prove to be a valuable way of treating a wide range of autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease, lupus and multiple sclerosis.

They also suggest that boosting IRF5 levels could help treat people whose immune systems are compromised or damaged.

“Our results show that IRF5 is the master switch in a key set of immune cells, which determines the profile of genes that get turned on in those cells,” Dr. Irina Udalova from the Kennedy Institute of Rheumatology at Imperial College London, the senior researcher on the study, said in a statement.

“This is really exciting because it means that if we can design molecules that interfere with IRF5 function, it could give us new anti-inflammatory treatments for a wide variety of conditions,” Udalova said.

“Diseases can affect which genes are switched on and off in particular types of cells. Understanding how this switching is regulated is crucial for designing targeted strategies to suppress unwanted cell responses,” she said.

The researchers said IRF5 seems to work by switching on genes that stimulate inflammatory responses and dampening genes that inhibit them. It can do this either by interacting with DNA directly, or by interacting with other proteins that themselves control which genes are switched on, the researchers explained.

Udalova’s team is now studying how IRF5 works at the molecular level and which proteins it interacts with so they can design ways to block its effects.

Rheumatoid arthritis affects about 1 percent of the world’s population and arises when the immune system mistakenly attacks joints all over the body. It may also affect the skin, heart, lungs, kidneys and blood vessels. Many who suffer get deformed hands and feet, which affects movement and the ability to function normally.

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