Cells' energy factories linked to damaging inflammation

Trish Reynolds, nih.gov, Monday January 31, 2011:

Scientists have discovered that molecules called reactive oxygen species (ROS) produced by the energy factories, or mitochondria, in cells, may play a role in a rare inherited disorder in which uncontrolled inflammation damages the body’s tissues.

Their research in human and mouse cells suggests that blocking these molecules could reduce inflammation in TNF receptor-associated periodic syndrome (TRAPS) and possibly other inflammatory diseases.

The work, published online in the Journal of Experimental Medicine, was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, a component of the National Institutes of Health.

TRAPS is one of a recently identified family of conditions referred to as autoinflammatory disorders, which are marked by unexplained inflammation. As discovered by Dr. Daniel Kastner’s research group in 1999, TRAPS is caused by mutations in the gene coding for TNF receptor 1 (TNFR1), which binds tumor necrosis factor (TNF). TNF is a key inflammatory molecule in the body’s response to infection, as well as in a number of common rheumatic diseases, including rheumatoid arthritis and ankylosing spondylitis. In people with TRAPS, TNF-mediated inflammation causes recurrent fevers, abdominal pain and skin rash. If not controlled, inflammation can lead to amyloidosis, a buildup of inflammatory proteins that can result in organ damage.

While blocking TNF with agents called TNF-inhibitors relieves symptoms for some patients, others continue to have symptoms, says Richard Siegel, M.D., Ph.D., NIAMS autoimmunity branch chief and acting clinical director. Some go on to develop amyloidosis despite treatment.

The inadequacy of anti-TNF treatment in these patients led Dr. Siegel and his colleagues to look at ROS. ROS are chemically reactive molecules containing oxygen that have been implicated in a variety of conditions, including cancer and atherosclerosis. Read more>>