New research from Brigham and Women’s Hospital (BWH) and Queen Mary, University of London recently revealed that the body converts an ingredient found in fish oils into a chemical mediator called Resolvin D2 (RvD2). The researchers discovered the complete chemical structure of RvD2, which could have major clinical implications for the treatment of a number of diseases related to inflammation. In contrast to other anti-inflammatory drugs, this chemical signal does not appear to suppress the immune system. These findings are published in the October 29 issue of Nature.
“These results uncover new anti-inflammatory and pro-resolving mechanisms in host defence that protect from uncontrolled inflammation, as in sepsis,” said Prof. Charles Serhan, director of the Experimental Therapeutics and Reperfusion Injury Center at BWH.
The researchers found that the body converts an ingredient in fish oils, docosahexaenoic acid (DHA) into RvD2. DHA, an omega-3 fatty acid, is an essential nutrient that humans do not produce and thus is obtained through one’s diet. Earlier results showed that omega-3 fatty acids are converted to novel anti-inflammatory mediators, coined resolvins. In this study, researchers determined a number of ways RvD2 relieves inflammation and that it does so powerfully with very small amounts.
In nearly all cases, the fundamental cause of tissue damage from inflammation is the excessive accumulation of white blood cells (leukocytes), which migrate from the bloodstream to the site of infection or injury by sticking to the inner lining of the blood vessels, called the endothelium. In this study, the research team looked at how RvD2 stopped inflammation, by assessing its actions on the activity of the body’s leukocytes and how they interact with the endothelium. They found that RvD2 causes endothelial cells to produce small amounts of nitric oxide, which act as a chemical signal discouraging the leukocytes from sticking to the endothelial cells and preventing inflammation.
“These direct vascular actions of RvD2 also have implications for cardiovascular diseases such as atherosclerosis, where deficiencies in nitric oxide production and excessive leukocyte adhesion are a prominent disease components” said Dr. Matthew Spite, the lead author on this study. Importantly, in addition to preventing excessive leukocyte infiltration, “We also discovered that RvD2 helped leukocytes ‘clear-up’ bacteria, preventing overwhelming infection, thus RvD2 may potentially show beneficial outcomes in treating other diseases of bacterial origin” said Dr. Lucy Norling, a co-author on this study.
These results showed us how omega-3 fatty acids in fish oils can be used by the body to produce very powerful local chemical signals that control the inflammatory response. Potentially, RvD2 could be used as an agonist to stimulate resolution of acute inflammation and clear invading bacteria. This may be important not only to treat uncontrolled acute inflammatory diseases, but possibly many other more complex diseases associated with inflammation, like sepsis or even periodontal diseases, without causing immune-suppression.
This study was funded by the National Institutes of Health, Arthritis Research Campaign UK and the Wellcome Trust.