Researchers and health practitioners have known that regular, moderate exercise has a positive impact on the body’s response to inflammation; but the exact cause for this effect has remained a mystery.
Now, a new study, from researchers of York University’s School of Kinesiology and Health Science in Canada, has discovered that answers may lie in the production level of macrophages—white blood cells that are responsible for killing infections and healing injuries. Published in Cell Physiology, this study has found that exercise of moderate intensity trains the precursors of macrophages in bone marrow.
Dr Ali Abdul-Sater, associate professor and York research chair explained, “Much like if you train your muscles through exercise, we showed that exercise of moderate intensity ended up training the precursors of those macrophages in the bone marrow. The way that exercise is doing this is by changing the way those cells breathe, essentially, how they use oxygen to generate energy and then changing the way they access their DNA.”
Inflammation is the body’s response to infection and other stressors. While we often hear about inflammation in the context of its negative effects, it’s actually a natural response that is necessary and desirable. As Dr Abdul-Sater explains, “Inflammation is amazing; it's a very important part of our normal immune response. What we're concerned about is excessive inflammation. Heart disease, diabetes, many cancers and autoimmune diseases, all essentially begin because there was an inappropriate inflammatory response."
For this study, researchers split female mice into two groups—one that exercised on a treadmill for one hour per day and the other that did not exercise at all. Both exercise regimes lasted for eight weeks, after which bone marrow-derived macrophages (BMDMs) from both groups were collected. These samples were put through various tests to assess their inflammatory and antiviral responses.
Analysis of the results showed that gene expression of inflammatory genes in exercised mice’s BMDM’s, was significantly lower than in sedentary mice, due to changes in the accessibility of those genes for transcription. Researchers also noted that exercise inhibited other pathways linked to inflammation compared to the control group.
To understand whether these effects could be maintained in the long term, the researchers examined BMDM’s from exercised mice after they stopped the exercise regimen. As expected, the inflammation levels were found to be at the same level of the sedentary mice, leading the researchers to infer that exercise was an important factor.
“There's a lot of rewiring that's taking place in the circuitry of how the cells breathe, how the cells metabolise glucose, how the cells then access DNA. So all that just takes time,” explained Dr Abdul-Sater regarding the eight-week period of exercise which the mice were put through.
As the inflammatory response is a very ancient one, this aspect of the immune system is generally very similar across mammals. Dr Abdul-Sater expects that the research would translate well to humans. In the next phase, researchers from the university will collect immune cells from human volunteers who will do exercises of various intensities to see which workout routines are most beneficial to balance the inflammatory response. They will also look at inflammation in mice in more complex infectious diseases similar to COVID and other auto-immune diseases, where overactive inflammatory responses lead to poor outcomes.
“People that got seriously ill from COVID, went into what is called a cytokine storm, essentially they released this massive number of cytokines, those mediators that are produced by inflammatory cells, which then cause that accumulation of fluid in lungs,” Dr Abdul-Sater said. “The thing with humans is there's no intervention that will work on everyone. We know that, but what this study suggests is that moderate and persistent exercise not only improves metabolic health, but also will improve immune health in the long run.”
While the findings that exercise is beneficial will not come as a surprise, Dr Abdul-Sater hopes that, by finding the underlying mechanisms of the beneficial impact, this knowledge would, in turn, be put to good use.
