Harvard Magazine

IN 2007, associate professor of medicine Samia Mora and colleagues published a study of exercise that sought to understand why physical activity is salutary. They already knew that exercise reduces the risk of cardiovascular disease as much as cholesterol-lowering statin drugs do. By analyzing biomarkers in the blood of 27,055 women participating in a long-term study, and other objective measures, they hoped to tease out the source of this effect. How much of the benefit was attributable to improved blood pressure? To lower body weight? Or to something else? The women had donated blood in the 1990s when they entered the study. Eleven years later, the researchers analyzed this frozen blood to see if they could find anything that correlated with long-term cardiovascular outcomes such as heart attack and stroke. “We were actually surprised that reduced inflammation was the biggest explainer, the biggest contributor to the benefit of activity,” says Mora, “because we hadn’t hypothesized that. We knew that regular exercise does reduce inflammation over the long term, but we also knew that acute exercise transiently increasesinflammatory biomarkers during and immediately after exertion.” About a third of the benefit of regular exercise, they found, is attributable to reduced inflammation.

The anti-inflammatory effect of exercise was much greater than most people had expected. That raised another question: whether inflammation might also play a dominant role in other lifestyle illnesses that have been linked to cardiovascular disease, such as diabetes and dementia.

In 2017, two cardiologists at Brigham and Women’s Hospital in Boston, who suspected such a link, published the results of a human clinical trial that will forever change the way people think about inflammation. The trial, which involved more than 10,000 patients in 39 countries, was primarily designed to determine whether an anti-inflammatory drug, by itself, could lower rates of cardiovascular disease in a large population, without simultaneously lowering levels of cholesterol, as statin drugs do. The answer was yes. But the researchers went a step further, building into the trial additional tests seeking to clarify what effect the same anti-inflammatory drug, canakinumab, might have on illnesses seemingly unrelated to cardiovascular disease: arthritis, gout, and cancer. Only the researchers themselves, and their scientific colleagues, were unsurprised by the outcome. Lung cancer mortality dropped by as much as 77 percent. Reports of arthritis and gout also fell significantly.

In medicine, believing something is true is not the same as being able to prove it. Because the idea that inflammation—constant, low-level, immune-system activation —could be at the root of many noncommunicable diseases is a startling claim, it requires extraordinary proof. Can seemingly unconnected illnesses of the brain, the vasculature, lungs, liver, and joints really share a deep biological link? Evidence has been mounting that these common chronic conditions—including Alzheimer’s, cancer, arthritis, asthma, gout, psoriasis, anemia, Parkinson’s disease, multiple sclerosis, diabetes, and depression among them—are indeed triggered by low-grade, long-term inflammation. But it took that large-scale human clinical trial to dispel any lingering doubt: the immune system’s inflammatory response is killing people by degrees.

Now the pertinent question is why, and what can be done about it. The pharmaceutical industry is deeply interested in finding ways to stop inflammation with medicines like canakinumab, an orphan drug that blocks a specific pro-inflammatory pathway called IL-1beta. But some researchers suggest that the inflammatory process—a normal and necessary part of the natural immune response—has itself has been misunderstood. Scientists know that the process can be turned on and off, but have only recently understood that this doesn’t mean normal physiology will resume once the inflammation caused by infection, injury, or irritant has been shut down. Instead, the restoration of health is an active phase of the inflammatory process itself, facilitated by a little-known class of molecules called pro-resolving mediators—the protectins, resolvins, maresins, and lipoxins—brimming with marvelous, untapped, regenerative capacities…Read More at

Harvard Magazine