On 1 March 1987, thousands of runners took to the streets of Los Angeles for the annual city marathon, unaware that many of them were about to provide crucial evidence for a study that would inspire three decades of research into the relationship between exercise and the immune system.

Monitoring the race closely was David Nieman, a scientist at Appalachian State University in North Carolina, and a keen marathon runner himself with a PB of 2:37. Nieman had become interested in the connection between intense exercise and our susceptibility to colds or viruses some years earlier after suffering a debilitating bout of flu while at the peak of his training for an upcoming race.

Intrigued as to whether there was a link, he got in touch with the organisers in Los Angeles, detailing his plans to set up a study monitoring the competitors and recording how many fell foul of infection both before and after the race, compared to non-runners in the same city at the same time.

Over 2,000 of the competitors that year took part in his study, and the results seemed to confirm Nieman’s suspicions: nearly 13% fell ill in the week following the race compared to just 2% of the normal population.

Nieman’s results paved the way for a theory called the “elite athlete paradox”. While exercise is good for physical and mental health, extremely intense exercise can actually lead to a suppression of the immune system for a couple of hours – an open window for infection.

When Nieman published his findings in 1990, the elite athlete paradox was a groundbreaking new idea, leading to a wealth of interest from human performance experts to immunologists who began researching the underlying molecular processes in more detail than ever before.

They found that exercise actually stimulates a powerful anti-inflammatory response, a key part of the body’s naturally built-in healing processes. While intense, long duration exercise sends this response into overdrive – thus temporarily compromising the body’s ability to defend itself – regular moderate-intensity exercise can combat the low-grade inflammation underpinning many chronic diseases ranging from diabetes and cardiovascular disease to dementia, various cancers and depression.

From an evolutionary perspective, it’s thought that this anti-inflammatory reaction occurs because our bodies have evolved with movement. Regular bursts of moderate-to-high intensity exercise have formed part of our daily lives for most of the past 200,000 years, acting as a natural cleansing mechanism from any lingering inflammation.

Inflammation has developed a bad name in recent years but, as a natural response to injury or illness, it’s a controlled, protective process that keeps us alive. In the short term, it induces symptoms such as heat, pain and swelling, but this kills dangerous microbes and simultaneously stimulates bodily repair and regeneration.

The silent, more dangerous form is chronic, low-level inflammation, which can arise due to a combination of factors. Genetic predisposition, stress, disrupted sleep patterns, modern diets and lifestyle elements such as smoking and alcohol abuse have all been implicated. And with 21st century life more sedentary than any previous time in human history, this is typically allowed to smoulder away unfettered. As a result, over time, the very processes designed to protect us begin to malfunction.

While at the University of Loughborough, João Viana researched the impact of exercise on chronic kidney disease, an incurable condition that affects around 6% of men and 7% of women, often leading to cardiovascular problems.

“Inflammation underpins most of these chronic diseases,” he says. “And it makes these patients very vulnerable to small, minor infections. Because their cells are so inflamed, their immune system is constantly switched on and, when it has to actually respond to a bacteria or a virus, it doesn’t handle it so well. In healthy individuals, the effect of exercise is to give a boost to the immune system, but for someone with a chronic condition, they first have to get their immune system back to normal and the anti-inflammatory effect can help with that. In our studies, we see the beginnings of this after just 30 minutes of walking on a treadmill. Big improvements then follow after six months of regular exercise.”

To fully understand the anti-inflammatory benefits of exercise, we need to look at the intricate signalling processes taking place down at the molecular level. The key players in these chains of events are proteins called cytokines: messengers that interact with the cells of the immune system and regulate the body’s pro- and anti-inflammatory responses.

One of the most important consequences of exercise is the release of large quantities of a particular protein called Interleukin-6, a multi-functional cytokine that is derived specifically from muscle tissue. The greater the duration and intensity of the workout, the more Interleukin-6 is produced. In this instance, Interleukin-6 acts as a powerful hub, switching off other cytokines involved in inflammation and stimulating those that control anti-inflammatory responses.

It also works in conjunction with the motor centres in the brain to stimulate the adrenal glands via the activation of different pathways in the nervous system. These glands, located above the kidneys, release a hormone called cortisol into the bloodstream, which stops the immune cells producing pro-inflammatory cytokines.

As well as affecting which proteins are turned off and on in the bloodstream, exercise also affects the movement and abundance of immune cells in the fat tissue, a particularly important role as the accumulation of fat leads to the production of pro-inflammatory fat molecules called adipokines. These maintain a persistent level of inflammation that is enhanced further by the movement of immune cells – such as white blood cells, which wrongly assume the inflammation is a sign of injury or infection – into the fat tissue. Exercise stops this migration in its tracks and reduces the amount of fat stored in the abdominal regions, and thus the production of adipokines.

But why do athletes who complete marathons or undergo consistently intense training regimes experience a momentary weakening of the immune system? This is because for such durations of exercise, the natural anti-inflammatory response is amplified far beyond usual levels. Large amounts of an anti-inflammatory cytokine called Interleukin-10 are released and, in these quantities, this molecule weakens the body’s defences to bacterial or viral pathogens.

However, this simply means that these athletes have to be slightly more cautious about their health during training and competition. Nieman and others also now believe there are ways of counteracting the effects of Interleukin-10, through natural plant molecules such as quercetin. This is a powerful antioxidant contained in apples, blueberries, onions, kale and broccoli, and it is five times more powerful than vitamin C. One study of 40 cyclists who took 1000mg of quercetin daily before, during and after a particularly intense training camp, showed they had a much lower incidence of illness in the weeks after the camp.

“Marathon running can also lead to the production of too much cortisol,” Viana says. “Like Interleukin-10, this can suppress the immune system, but there’s evidence you can blunt its effects by making sure you maintain your carbohydrate levels as much as possible during and after exercise. But these things are also related to psychological stress – you have to try to keep that to a minimum and make sure you get adequate sleep as the circadian rhythms can have a big effect on your immune response.”