"Better to stimulate its resolution than to prevent its triggering …"

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For Charles Serhan of Harvard Medical School, the discovery of the SPM family – resolvin, protectins … – offers the hope of controlling inflammation in a precise and safe way.

Interviewed by Florence Rosier Posted yesterday at 10h09, updated yesterday at 18h48

Time to Reading 5 min.

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Charles Serhan is Professor of Anesthesia at the Harvard School of Medicine and Immunology at Harvard School of Dentistry (Massachusetts, USA). He also runs a center for experimental therapy for ischemia-reperfusion injury at Boston's Brigham and Women's Hospital. For twenty-five years, he has been exploring the cellular and molecular mechanisms of inflammation resolution. He discovered a superfamily of molecules, the SPMs, produced by the body after the acute phase of inflammation. Their mission: to extinguish this fire.

You have discovered a whole family of molecules "firefighters of inflammation". When and how do they intervene?

Normally, the inflammatory response is protective: its role is to defend the body against aggression (infection, trauma …). Once this mission accomplished, in principle, it solves spontaneously. It has long been thought that this process was passive, but it is not: it involves an active and coordinated program. My research focused on the molecules that control it. In the 2000s, my team discovered resolvin, then protectins and marines. With lipoxins, they form a superfamily, the SPM ("specialized pro-resolving mediators"). They stimulate the resolution of inflammation and reduce the associated pain. Many also help to resolve infections and regenerate tissue. All are lipids (fat molecules), which makes it a separate signaling mode.

What happens when the inflammation persists with low noise?

It happens indeed – it is even frequent – that the inflammation does not resorb. Why ? The possible causes are numerous. It may be because the aggression factor persists itself (latent infection, excess of fat and sweet food, chronic exposure to toxins …). Or the SPMs are overwhelmed, ineffective, or they are not produced. Certain diseases or deficiencies of the immune system also come into play.

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What are the medical promises related to the discovery of PMS?

The discovery of these molecules opens the hope of controlling inflammation in a more precise and safer way. Because rather than preventing inflammation, it is better to stimulate the resolution. Today anti-inflammatory drugs are widely used. But they block our natural defenses: hence their many adverse effects – immunosuppression and infections, especially. In contrast, PMS allow inflammation to accomplish its defense mission, then they terminate the process and clear the battlefield. Their use could thus avoid the long-term sequelae of persistent inflammation, without the undesirable effects of conventional anti-inflammatory drugs.

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