Cardio Curbs Excessive Inflammation in Surprising Ways

Although exercise physiologists have known for a long time that doing cardio tempers the body's inflammatory responses, until recently researchers weren't sure exactly how aerobic exercise tones down excessive inflammation.

New research in mice gives some fresh clues about how long-term physical activity tempers inflammatory responses after a few weeks of consistent exercise. The findings (Murugathasan et al., 2023), by a team of researchers from York University's School of Kinesiology and Health Science, were published on June 12 in the American Journal of Physiology-Cell Physiology (AJP-Cell).

Using a mouse model, the Canadian researchers found that moderate-intensity aerobic exercise reprograms the metabolic activity of bone-marrow-derived macrophages (BMDMs), which triggers anti-inflammatory responses. BMDMs are large white blood cells that have many functions involving the immune system and inflammatory responses.

Humans and Mice Have Similar Inflammatory Responses

Because the inflammatory response is very similar across mammals, the researchers posit that their findings in mice will be similar to those in humans. In humans and mice, bone-marrow-derived macrophages play a vital role in initiating and resolving inflammation.

"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," senior author Ali Abdul-Sater said in a June 2023 news release. "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."

Although acute, short-term inflammatory responses play an important role in healthy immunity, long-term chronic inflammation is problematic. As Abdul-Sater explains, "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 the study on how moderate exercise influences the inflammatory response in macrophages, the researchers compared BMDMs in a group of exercised mice, which regularly ran on running wheels for a few months, with those of a control group of sedentary mice, which didn't exercise regularly during the time period.

Six to Eight Weeks of Daily Cardio Reprograms Macrophages

After about six to eight weeks, changes in how the bone-marrow-derived macrophages tempered the inflammatory response in exercised mice—but not in the control group of sedentary mice—became "really apparent" to the researchers.

As the authors explain, "[Our findings] show that chronic moderate-intensity training of mice leads to persistent metabolic rewiring and changes to chromatin accessibility in bone-marrow-derived macrophages, which, in turn, tempers their inflammatory responses."

Notably, the BMDMs from exercised mice exhibited a decrease in pro-inflammatory gene expression along with an increase in debris-removing associated genes. Compared to BMDMs from sedentary mice, the macrophage changes in the exercised mice were also associated with improved mitochondrial quality and reduced mitochondrial reactive oxygen species production.

Based on the findings, the authors conclude: "Overall, our data suggest that chronic moderate exercise can influence the inflammatory responses of macrophages by reprogramming their metabolic and epigenetic landscape."

Human Studies Are Needed to Confirm the Findings in Mice

For the next phase of their research into the effects of exercise on immunity in macrophages, Abdul-Sater and colleagues will have human volunteers do cardio workouts at various intensities and durations. Then they'll collect and analyze their immune cells to pinpoint the precise "dose" of aerobic exercise that's most beneficial to our inflammatory responses.