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Lipoxins and new lipid mediators in the resolution of inflammation.

Schwab JM, Serhan CN (2006) Curr Opin Pharmacol.  6(4): 414-20 

Web URL: View this abstract via PubMed here

Abstract:

Lipoxins and aspirin-triggered lipoxins are lipid mediators generated from arachidonic acid that act to reduce inflammation and promote resolution.

In addition, two new families of lipid mediators were uncovered, namely resolvins (resolution phase interaction products) and protectins, which derive from omega-3 polyunsaturated fatty acid. They possess potent anti-inflammatory, neuroprotective and pro-resolving properties.

Eicosapentaenoic acid-derived mediators are denoted resolvins of the E series, and those biosynthesized from docosahexaenoic acid are resolvins of the D series (RvDs) and protectins.

Aspirin impinges on these systems, triggering formation of the epimeric 17R-series RvDs - denoted as 'aspirin-triggered-RvDs' - which possess bioactivity in vivo equivalent to that evoked by their 17S-series counterparts (i.e. RvDs).

These bioactive molecules open new avenues and approaches to therapeutic interventions via accelerated resolution of inflammation.

FAB RESEARCH COMMENT:

Omega-3 and omega-6 fatty acids are the two main types of polyunsaturated fats, and the only types of fat that are essential nutrients. (They are critical for brain and body health, but humans cannot make them, so they must be provided by the diet).

Both omega-3 and omega-6 are needed not only for the normal structure and function of all cell membranes (particularly those in the brain and nervous system), but also as vital raw materials for a huge array of regulatory substances that influence almost every aspect of our biochemistry and physiology, from gene expression and regulation to blood flow, hormonal balance and the functioning of our immune systems.

Some of these substances dervided from omega-3 and omega-6 fats (including prostaglandins, leukotrienes and thromboxanes) have been known and studied for decades. 

For example, both aspirin and the non-steroidal anti-inflammatory drugs (NSAIDs) used to treat inflammatory conditions work by reducing the activity of enzymes that make pro-inflammatory substances from arachidonic acid (AA) - the main long-chain omega-6 fatty acid (found in meat. eggs and dairy produce, or derived from the simpler omega-6 found in all vegetable oils).  These drugs also help trigger the production of other substances made from AA (lipoxins) that help to resolve inflammation.
   
However, far less inflammatory substances would be made in the first place if more of the long-chain omega-3 EPA, rather than omega-6 AA, were available for the very same enzymes to work on.
  • This means that simply reducing the huge excess of omega-6 vs omega-3 fats found in typical modern, western-type diets - leading to less AA and more EPA in the body and brain - can reduce inflammation, and in some cases may reduce the need for anti-inflammatory drugs, which can often have negative side-effects.

This new study reviews the most recent discoveries of yet more regulatory substances made from the long-chain omega-3 fatty acids EPA and DHA, which actively help to resolve inflammation and reduce the associated cellular damage. 

These newly-discovered substances effectively quench inflammation - in much the same way that water can help extinguish a fire.  Until their discovery, it was not fully recognised that resolving inflammation, i.e. bringing it to an end, is an active process.  And it requires substances made from omega-3 EPA and DHA - wich have to be provided by the diet.

Appropriately, some of these newly discovered 'lipid mediators' have been named 'resolvins' and 'protectins'.

The ongoing study of these and other derivatives of the long-chain omega-3 and omega-6 fatty acids clearly offers important new avenues for developing better treatments for inflammatory disorders.

It also acts as a reminder that good health depends very fundamentally on nutrition and diet.