Exercise, lifestyle activity and immune-mediated chronic inflammation

Inflammation is part of the body’s defence mechanism and is broken down into acute and chronic inflammation. Acute inflammation refers to rapid inflammation that lasts for a few days, usually due to tissue damage or infection, and results in symptoms such as coughing and sneezing. Acute inflammation helps fight infection and clear local tissue damage, such as muscle damage that can occur after strenuous unaccustomed exercise.

Chronic inflammation is slow, long-term inflammation lasting for months, years or a lifetime. It can result from unresolved episodes of acute inflammation, caused by: sustained exposure to a low level of irritant - such as high levels of circulating fats or pollutants such as those from smoking; low levels of oxygen in tissue as can happen in fat tissue in cases of obesity; autoimmune disorders where the immune systems attack healthy tissue due to miscategorising it as an issue; and unresolved infections.

Importantly, chronic inflammation is associated with a small, yet persistent increase in circulating inflammatory proteins, which is present over months and years and can be assessed to evaluate the impact of interventions to lower chronic inflammation. Conventional drugs such as statins, non-steroidal anti-inflammatory drugs, and corticosteroids can block pro-inflammatory mechanisms within the body. However, it has also been shown that physical exercise has anti-inflammatory effects on the body, even with small amounts of activity, and without weight loss.

Chronic inflammation and obesity

Fat tissue is a major source of the pro-inflammatory proteins that go around the body causing harm. Excessive movement of immune cells into fat tissue underpins the release of the pro-inflammatory proteins. We have reported that this movement of cells into the tissue is higher in people with obesity, but this was reduced in those with obesity who were also regularly active.

This shows that physical activity is an important method to reduce migration of immune cells into surrounding tissue in people with obesity, which may reduce the amount of pro-inflammatory proteins that the fat tissue produces, reducing inflammation and decreasing disease risk.

We are now conducting ongoing research to see if this is more prevalent in those of South Asian ethnicity, given this group has a high-risk for cardiovascular disease and diabetes.

Chronic inflammation and kidney disease

Most people with kidney disease die from cardiovascular disease, rather than kidney failure. This is a consequence of the kidneys not working properly, resulting in higher levels of toxins in the blood that can stimulate the development of chronic inflammation, which in turn increases the risk of cardiovascular disease.

Working with colleagues from the University of Leicester and University Hospital’s Leicester NHS Trust, we have shown that walking regularly for people with early stage (non-dialysis) chronic kidney disease lowers the activation of inflammatory immune cells, as well as the amount of pro-inflammatory proteins in the blood.

We have also looked at effects of exercising while receiving haemodialysis treatment and are involved in ongoing work looking at the effect of home-based exercise programmes on chronic inflammation in people who have received a kidney transplant. Our work in this area has contributed to the recently published Renal Association Clinical Practice Guideline for Exercise in Chronic Kidney Disease.

Inflammatory arthritis

Axial spondyloarthropathy (AS) is a painful, progressive form of inflammatory arthritis, which mainly affects the spine, hips and pelvis, but can also influence peripheral joints such as the fingers and ankles. In extreme cases, the vertebra of the spine can fuse together significantly reducing mobility.

The condition effects around 0.8% of the UK population, making it more prevalent than Parkinson's and Multiple sclerosis (MS), and is associated with severe pain, fatigue, mental health issues, and other diseases such as cardiovascular disease. However, it is thought to be underdiagnosed, with the average age of symptom onset just 26 and an average delay of diagnosis of 8.5 years. This delay costs the UK economy £18.7 billion a year.

The main treatment for the condition is anti-inflammatory medication. However, the effects of physical activity on immune cells in this population are unknown.

Academics at Loughborough are currently running a pilot project, funded by the National Axial Spondyloarthropathy Society (NASS), to investigate whether the use physical activity can reduce the proportion of pro-inflammatory immune cells and improve symptom burden. Ten patients have been randomly assigned into a usual care (control) group, and 10 into an exercise group where they are asked to walk for 30 minutes, 5 times per week, at a pace which is somewhat hard.

Preliminary results suggest that physical activity does reduce the proportion of pro-inflammatory immune cells and reduces spinal pain and disease activity. These results were recently presented at the British Society of Spondyloarthropathy, winning the annual basic science prize.

Feedback from the participants is also reassuring. There has been a 0% drop out so far and participants have been positive about the project, stating that it has helped them learn about AS, and has also made their families more aware of what AS is. The results of the project will be published in 2023.

Physical activity, sedentary behaviour, acute stress and inflammatory responses

In addition to physical inactivity, sedentary behaviour and psychological stress are also risk factors for cardiovascular disease that are characterised by chronic inflammation.

Members of our team are conducting an on-going programme of research investigating these interrelationships to look at how inflammatory responses to acute stress are affected by differing levels of sedentary behaviour and physical activity, as well as the effect of breaking up sitting time with resistance exercise.