Inflammation can manifest in two forms: acute and chronic. While acute inflammation is a necessary response to injury or infection, chronic inflammation, on the other hand, can be detrimental as it affects healthy tissues or persists for an extended duration. Inflammation is associated with many diseases, including cardiovascular diseases, gastrointestinal disorders, lung diseases, mental illnesses, certain types of cancer, and more.
While researchers have recognized for a considerable time that moderate exercise positively affects the body’s inflammatory response, the precise underlying mechanisms have remained unclear. In this article, we will explore the reasons behind the beneficial impact of exercise on inflammation.
The Connection Between Exercise and Inflammation
Scientists have been aware for a while that moderate exercise has positive effects on how the body deals with inflammation. However, the reasons behind this have remained unclear. Recent research conducted at York University using mice suggests that the explanation may involve the production of macrophages. These are special white blood cells that play a crucial role in fighting infections, promoting healing, and acting as the body’s first line of defense.
Ali Abdul-Sater, an Associate Professor in the Faculty of Health and York Research Chair at the School of Kinesiology and Health Science said “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.”
While numerous studies investigate the impermanent immune system enhancements following exercise, the findings of this study, published in the journal AJP-Cell, demonstrate that these changes persist even after a week, indicating their long-term nature.
A certain degree of inflammation is essential and beneficial for the body. Emphasizing this statement Abdul-Sater said “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.”
According to his observations, noticeable changes in the mice occurred approximately six to eight weeks into the exercise regimen, highlighting a clear contrast with sedentary mice, “There’s a lot of rewiring that’s taking place in the circuitry of how the cells breathe, how the cells metabolize glucose, how the cells then access DNA. So all that just takes time.”
Future Directions in Research
Abdul-Sater highlights the universality of the inflammatory response across mammals due to its ancient nature, indicating that the findings are likely to be applicable to humans as well. In the upcoming phase of their research, Abdul-Sater and other collaborators plan to gather immune cells from human volunteers who will engage in exercises of different intensities. This investigation aims to determine which workout routines are most effective in achieving a balanced inflammatory response. Additionally, they will explore inflammation in mice models that simulate more intricate infectious diseases like COVID-19 and autoimmune disorders, where excessive inflammatory responses contribute to unfavorable outcomes.
“People that got seriously ill from COVID-19, 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.”
Although it may not be unexpected to learn that exercise offers benefits, Abdul-Sater expresses the aspiration of utilizing the understanding of the underlying mechanisms behind these positive effects for practical purposes.
“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.”
Moderate Exercise: Inducing Trained Immunity in Macrophages
In a study, it was demonstrated that long-term moderate-intensity training in mice results in enduring metabolic adaptations and alterations in chromatin accessibility within bone marrow-derived macrophages (BMDMs). As a result, these changes modulate the inflammatory responses exhibited by the BMDMs.
In the findings, it was indicated that BMDMs derived from mice that underwent exercise displayed reduced activation of NF-kB and decreased expression of pro-inflammatory genes when exposed to lipopolysaccharide (LPS), in contrast to BMDMs from sedentary mice. Additionally, the BMDMs from exercised mice exhibited an increase in genes associated with the M2-like phenotype. These effects were linked to enhanced mitochondrial quality, greater reliance on oxidative phosphorylation, and a reduction in mitochondrial ROS production.
By employing ATAC-seq analysis, alterations in the chromatin accessibility of genes linked to both inflammatory and metabolic pathways were observed, providing mechanistic insights into the observed changes.
Takeaway
Through this research, we have gained insights into the ways in which moderate exercise can alleviate inflammation. Evidence suggests that the inflammatory responses of macrophages can be influenced by regular moderate exercise through the reprogramming of their metabolic and epigenetic landscape. This study provided an explanation for why exercise is beneficial in reducing inflammation.
