A new study has shown that human muscle can ward off the damaging effects of chronic inflammation when exercised.
Carried out by biomedical engineers at Duke University, the study used lab-grown, engineered human muscle to show that it autonomously blocks the damaging effects of a pro-inflammatory molecule – interferon gamma – which has been associated with various types of muscle wasting and dysfunction.
Low-level inflammation can be created when the body is injured to clear away debris and rebuild tissue, however, sometimes the immune system overreacts and creates an inflammatory response that causes damage, like the often deadly cytokine storms brought on by some cases of COVID-19. There are also diseases that lead to chronic inflammation, such as rheumatoid arthritis and sarcopenia, which can cause muscle to waste away and weaken its ability to contract.
The study has been published in Science Advances.
Interferon gamma
Previous research in humans and animals has shown that exercise can help mitigate the effects of inflammation in general, it has been difficult to distinguish what role the muscle cells themselves might play, let alone how they interact with specific offending molecules, such as interferon gamma.
For the study, the researchers took the fully functional, lab-grown muscles and inundated them with relatively high levels of interferon gamma for seven days to mimic the effects of a long-lasting chronic inflammation, which caused damage, then applied interferon gamma again, but this time also put the muscle through a simulated exercise regime by stimulating it with a pair of electrodes.
The findings showed that it almost completely prevented the effects of the chronic inflammation. They then showed that simulated exercise inhibited a specific molecular pathway in muscle cells, and that two drugs used to treat rheumatoid arthritis, tofacitinib, and baricitinib, which block the same pathway, had the same anti-inflammatory effect.
Nenad Bursac, professor of biomedical engineering at Duke, said: “Lots of processes are taking place throughout the human body during exercise, and it is difficult to tease apart which systems and cells are doing what inside an active person. Our engineered muscle platform is modular, meaning we can mix and match various types of cells and tissue components if we want to. But in this case, we discovered that the muscle cells were capable of taking anti-inflammatory actions all on their own.”
“We know that chronic inflammatory diseases induce muscle atrophy, but we wanted to see if the same thing would happen to our engineered human muscles grown in a Petri dish,” said Zhaowei Chen, a postdoctoral researcher in Bursac’s laboratory and first author of the paper. “Not only did we confirm that interferon gamma primarily works through a specific signalling pathway, we showed that exercising muscle cells can directly counter this pro-inflammatory signalling independent of the presence of other cell types or tissues.”
“When exercising, the muscle cells themselves were directly opposing the pro-inflammatory signal induced by interferon gamma, which we did not expect to happen,” added Bursac. “These results show just how valuable lab-grown human muscles might be in discovering new mechanisms of disease and potential treatments. There are notions out there that optimal levels and regimes of exercise could fight chronic inflammation while not overstressing the cells. Maybe with our engineered muscle, we can help find out if such notions are true.”
