Protein master switch found for key immune cells in inflammatory diseases

n January 2011, scientists at the Imperial College, London, announced an important new discovery about how the immune system regulates inflammation, or swelling. The new discovery involves a key protein that can essentially turn on or off inflammation, which they are referring to, fittingly, as a "master switch."

Inflammation is a key problem in a wide range of medical problems, particularly autoimmune disorders and arthritis, where the swelling itself is the key symptom to be addressed rather than a consequence of another underlying illness or wound in need of treatment. Rheumatoid arthritis, for instance, is a painful condition which must be treated with anti-inflammatory drugs to allow sufferers to lead a normal life. Currently, common drugs for people living with rheumatoid arthritis target a group of cytokine proteins called tumor necrosis factors (TNF), but this is only effective in about two-thirds of cases. According to

Reuters, that means at least one-third of people with these conditions (and possibly more, who have not fully responded to drugs but previously had no other options but to continue taking them anyway) are still waiting for a new, effective drug therapy to be delivered.

The new study targets a different protein, which is called Interferon Regulatory Factor 5 - or IRF5, for short. The IRF proteins help control cell growth and division, and also play important roles in the immune system. However, the Imperial College team also found that IRF5, in particular, helps control how the white blood cells in the immune system will respond to inflammation. They reported in the journal, Nature Immunology, that when IRF5 production increases, a type of white blood cell called a macrophage responds by stimulating inflammation further. Macrophages are a particular type of white blood cell which the immune system manufactures to target and remove dead cells and pathogens. In cases of harmful inflammation, as in rheumatoid arthritis and autoimmune disorders, such cells have effectively gone off course, targeting normal cells in the body as undesirable invaders.

What researchers are particularly excited about with respect to IRF5, though, is what happens when IRF5 is inhibited, or blocked. When IRF5 levels fall, they noticed the inflammation goes down, too. Drugs that inhibit certain protein-level functions in the body already exist and have had important effects against certain types of cancer, including several forms of leukemia and breast cancer. Scientists are hopeful that the new discovery will pave the way for development of important new types of anti-inflammatory drugs based on the same type of principle.