Synthetic version could one day treat range of inflammatory diseases.
Fish oil's reputation as a panacea has expanded in recent years, with studies showing benefits in ailments ranging from asthma to heart disease. How it works has has been a mystery, but a new study now helps to provide the answer, and suggests that aspirin could boost the beneficial effect even further.
Many of the diseases helped by fish oils have one thing in common: chronic inflammation, in which immune cells and molecular mediators flood tissues and can create damage. This can lead, for example, to the hardening of the arteries that spurs heart attacks and strokes.
"We know that this fish oil suppresses inflammation," says Stephen Prescott, director of the Huntsman Cancer Institute at the University of Utah in Salt Lake City, and an expert on lipids and inflammation. "The question is how does it do it? People have looked for more than 20 years."
Charles Serhan at Harvard Medical School in Boston and colleagues became intrigued by the problem in 1999, after seeing a study showing that fish oil protects against cardiovascular disease.
Subjects in that study had consumed a gram of fish oil each day. "They smelled like mackerel," said Serhan. But he noticed that almost all of the subjects were also taking aspirin to prevent strokes and heart attacks. Might the two substances be working together?
Subsequent research by Serhan and his colleagues has suggested that they do. Their work in human cells and in mice showed that omega-3 fatty acids in the fish oil are converted into lipids that seem to suppress inflammation. Aspirin speeds up that conversion.
The researchers have now pinned down the effect even further by focusing on one of the lipids, called resolvin E1. First they found that healthy human volunteers fed both aspirin and fish oil had resolvin E1 in their bloodstream. Then they created a synthetic form of the lipid and tested its properties.
The lipid inhibited the migration of particular human immune cells and dramatically reduced inflammation on the skin of rabbits. Serhan and his team believe that resolvin E1 works in the body to tone down inflammation, and report their results in The Journal of Experimental Medicine1.
"This is a really attractive and interesting hypothesis at this stage," says Prescott. Raymond DuBois, a lipid researcher at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, echoes that sentiment, calling the work "a great move forward".
Serhan is now working to prove that resolvin E1 does actually help to treat disease. His unpublished data so far show that the synthetic version works in a mouse model of periodontal gum disease. Such disease is driven by inflammation, which weakens the gums and causes teeth to fall out. Resolvin E1 counteracts the process, he says.
Serhan now aims to scale up and modify the manufacture of synthetic resolvin E1 so that it can be made cheaply in bulk, and he hopes to start human trials soon.
It's a powerful substance, comments Prescott. "All you need to do is make a little bit, and bang, you have an effect."
But resolvin E1 is "just the tip of the iceberg", Serhan adds. His group is also looking at the other lipids that derive from fish oil. He suspects that each one has a part to play in orchestrating the inflammatory response. Understanding how they work could lead to the development of a range of new drugs to counteract inflammation, he predicts.
Arita, et al. J. Exp.l Med. 201, 713 - 722 (2005).