Polyunsaturated fats linked to impaired immune response in burn victims

Certain derivatives of dietary fats are associated with negative, inflammatory outcomes

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For decades, Western society has hailed polyunsaturated fats, or PUFAs, as a pillar of a heart-healthy diet. While these fats offer numerous human health benefits, new research raises concerns over the breakdown of PUFAs in the body and its consequential impact on immune cell function.

Research published in the Proceedings of the National Academy of Sciences earlier this year by Dr. Cindy McReynolds and colleagues reveals that DiHOME, a metabolized version of the PUFA linoleic acid, can exacerbate burn injury by overstimulating the body’s biological defense system while blocking other critical functions.

Polyunsaturated fats are common in plant-based oils, nuts, and fish and are increasingly prominent in our diet through the consumption of corn-based processed foods. When we consume these food products, the body integrates and distributes dietary fats in different ways. Linoleic acid, the focus of McReynolds’s study, becomes highly concentrated in skin tissues, where it provides structure for cell membranes.

When these membranes come into contact with excessive heat or other disturbances, linoleic acid breaks down into various compounds known as metabolites. One important class of metabolites is dihydroxyoctadecenoic acid, colloquially referred to as DiHOME.

As far back as the 1990s, scientists have documented a link between burn injury and accelerated metabolism of linoleic acid. Furthermore, past studies correlate this fatty acid with reduced survival.

Yet, until McReynolds and her team entered the scene, the mechanism behind linoleic acid’s adverse effect on immune response had remained largely elusive.

“Nobody looked at the DiHOMEs,” stated McReynolds as she explained the motivation for her study during an undergraduate Q&A session.

Using mice as a proxy for the human body, the researchers tested DiHOME’s impact on immune response, hypothesizing that this downstream metabolite is responsible for poor burn injury recovery.

When comparing scalded to burn-free mice, McReynolds discovered that not only were more DiHOMEs present in the burn victims, but these compounds also hijacked the immune response, causing the body to wage war on itself.

Normally, white blood cells known as neutrophils serve as the first line of defense in the battle against infection. Afterward, monocytes and macrophages, other flavors of immune cells, swoop in to clean up the carnage.

“[The neutrophils] come in like a tank and blow the infection away,” McReynolds explained.

However, when present in high concentrations, DiHOMEs overstimulate the neutrophilic response. Like overzealous militants, the neutrophils madly fire in all directions, preventing their fellow monocytes and macrophages from safely performing their immunological duties.

Such results provide critical insight into the body’s response to severe injury and the modulating impact of dietary fats. Although further study is necessary with human subjects, this research paves the way for pharmaceutical solutions to enhance burn injury recovery.

Already, McReynolds and colleagues have explored the effect of halting DiHOME production in the first place, with promising results for eventual therapeutic use in humans.

Because PUFAS are so engrained into Western foods and dietary patterns and provide protective benefits at lower concentrations, limiting their consumption is an unlikely solution. As such, examining the linoleic acid metabolic pathway and the impact of individual constituents on burn injury and even other diseases that elicit an immune response will reap enormous health benefits.

Academic Citations

Bergmann, C. B., McReynolds, C. B., Wan, D., Singh, N., Goetzman, H., Caldwell, C. C., Supp, D. M., & Hammock, B. D. (2022). sEH-derived metabolites of linoleic acid drive pathologic inflammation while impairing key innate immune cell function in burn injury. Proceedings of the National Academy of Sciences, 119(13). https://doi.org/10.1073/pnas.2120691119