RA: Switching Off the Immune Response

Alpha defensins…are they doing something to help lessen inflammation? That’s the case, says new research from the University of Edinburgh.

As indicated in the April 18, 2016 news release, “In a study involving human cells, researchers at the University of Edinburgh have shown that alpha defensins are released by immune cells called neutrophils when they die. The alpha defensins are then taken up by other immune cells called macrophages. The team found that the compounds prevent macrophages from producing messenger molecules called cytokines, which drive inflammation.”

Mohini Gray, Ph.D., of the University’s MRC Centre for Inflammation Research, said: “This discovery opens the door to new approaches for the treatment and prevention of chronic inflammation. We are hopeful that with further research, these treatments could be exploited in the near future.”

Dr. Gray told OTW, “Over 10 years ago we wished to understand how dying cells that were then taken up by immune cells, called macrophages, could induce them to stop being inflammatory. We wanted to know about this because most inflammatory rheumatic diseases such as rheumatoid arthritis and psoriatic arthritis are ultimately driven by macrophages producing too many inflammatory proteins, called cytokines. If we could harness that power of the dying cell, we would have new ways to treat these diseases.”

“It took us about four years to discover that the active agent in the dying immune cells (called neutrophils) was a peptide called the alpha defensins. These are ancient peptides produced by neutrophils that fight infections. This was an added bonus, because most treatments for arthritis are immune suppressive and make patients more at risk of infection.”

“Over the last few years we have worked on understanding how the alpha defensins are able to so effectively stop macrophages in their tracks form making proteins. The answer is that they block a process called protein translation. This is a fundamental process in the cell and alpha defensins are very effective at doing it.”

The next step will be for us to find a way to deliver the peptide just where it’s needed, i.e., the joint that is inflamed. Alpha defensins can effectively prevent macrophages, from being inflammatory. If harnessed as a therapy it would both prevent excessive inflammation and infection. For patients undergoing joint replacement surgery this may be useful to ensure faster healing and reduced infection rates.”