Coping with modern life can sometimes feel like a remorseless treadmill. Many of us end up exhausted, with a vague feeling that all this pressure can’t be doing us any good. But we do it anyway, driven by the notion that stress is for wimps. And there’s always a glass of wine and a takeaway to look forward to at the end of the week. Big mistake. Far from being for wimps, physical and psychological stress are major triggers of a modern scourge that has been linked with every malady from heart disease, depression and chronic pain to neurodegenerative diseases.
That scourge is inflammation. Until recently, we have known little about how what starts as a protective immune process in the body goes awry, and there have been frustratingly few evidence-based suggestions on what we should do about it. But now we are starting to learn more about how the process works, how it connects body and mind, and what we might do to keep it in check. This new understanding is leading to treatments that may finally let us douse this constant fire — not by stopping it from happening, but by turning it off when it is no longer useful.
Such treatments could benefit the millions of people around the world who have chronic inflammatory conditions like rheumatoid arthritis, asthma and celiac disease. They could also assist those of us who want to have our cake, eat it and not end up inflamed. Finding a way to manage inflammation could help prevent modern life from damaging our long-term physical health.
“There’s no question, inflammation is everything,” says Charles Serhan, an immunologist at Harvard Medical School. “In the post-genomic era, understanding inflammation is the next frontier.”
Inflammation is the body’s first line of defense. Without it, we would be at the mercy of every pathogen going. When the body’s protective barrier has been breached by injury or infection, the classic inflammatory response brings redness, heat, swelling and pain. First, damaged cells secrete chemicals known as cytokines, which increase blood flow to the affected area and alert the rest of the immune system to prepare for a fight. Heat comes as a side effect of increased blood flow, redness as blood vessels dilate, bringing blood closer to the surface of the skin, and swelling happens as blood vessels become more permeable, allowing fluid and white blood cells to leak out and flood the tissue. These cells then attack and gobble up any invading pathogens, and later clear up the debris.
This basic response comes in different flavours, depending on what challenge the body is facing. If you sprain your ankle, for example, the joint swells and becomes hot, painful and difficult to move. If you have a cold, it is the blood vessels in the airways that swell, blocking the nose while inflammatory histamines stimulate mucus production, which in turn sets off coughs and sneezes. If you have flu, you get all of this, plus inflammation spreads throughout the body, causing joints and muscles to ache.
Throughout our evolutionary history, acute inflammation has mostly worked just fine, flaring up, tackling the problem and dying away again when the danger has passed. But now modern life is stacked against this delicate balance. Obesity, stress, pollution, bad diet and ageing can all tip us into a low-level state of inflammation that, rather than being confined to a specific tissue, keeps the entire body in a perpetual state of readiness for a threat that never comes.
This persistent background inflammation might not always make us feel ill, but it can store up problems for the future, from heart disease to type 2 diabetes and neurodegenerative disease. In 2008, immunobiologist Ruslan Medzhitov of Yale University dubbed this “para-inflammation” and argued that it is an unfortunate consequence of our longer, calorie-rich lives.
Stress is a particular problem. The hormone noradrenaline, which is released in anticipation of an impending life-or-death situation, sets off the same chain of events as an infection or injury. Yet although stresses passed quickly in our evolutionary past, these days many of us are walking around with a ticking time bomb of stress-induced inflammation that never quite goes away. “Chronic, low-grade inflammation is being discussed in our field as one of the main pathways linking stressful life conditions with disease,” says Nicolas Rohleder of Brandeis University in Massachusetts. Over the past few years, for example, Rohleder has found that the long-term strains of caring for a seriously ill family member, and a series of short-term stresses, both increase levels of inflammatory markers in otherwise healthy people.
Obesity is another inflammation-inducing modern disease. A small amount of body fat is healthy, and in fact necessary for regulating not just the immune system, but also appetite, mood and metabolism. Once the scales tip past 25 to 30 per cent body fat, however, the balance shifts. Body fat stores large quantities of inflammatory cytokines, and if there is too much fat on board, particularly around the organs, they can seep out, leading to ongoing, low-level inflammation. “Fat in large amounts is an inflammatory tissue,” says Derek Gilroy, an immunologist at University College London. “So you can envisage that lifestyle — eating the wrong food — throws these checks and balances out of kilter.”
Modern, high-sugar diets can also lead to gum disease. This can push the body into an inflammatory state that has been linked to an increased risk of atherosclerosis: fatty deposits in the arteries that are one of the main risk factors for heart attacks and strokes.
The longer these inflammatory markers hang around, the more likely they are to cause problems. These can be relatively minor, prolonging colds by keeping up the response when it is no longer needed, for instance. Or they can be life-threatening. A recent study of nearly 300 people found that inflammation is directly linked to the early stages of heart disease. Over the course of three years, people with higher levels of reported stress and stress-related brain activity, not only had higher levels of C-reactive protein, a marker of inflammation, but also had a greater risk of cardiovascular disease.
It seems that when there are higher levels of white blood cells in circulation, they get attracted to any fatty plaques accumulating in the arteries, making these more likely to build up and eventually rupture. This can lead the vessel wall to bleed and form a clot, which could go on to cause a heart attack or stroke.
Chronic inflammation might also increase the risk of depression. Many of the psychological symptoms that come with such inflammation — tiredness, malaise and a loss of appetite — look a lot like depression. Some people are beginning to wonder if a rumbling level of inflammation is behind at least some cases of depression and other mental health problems. This might be the reason why antidepressant drugs, which don’t reduce inflammation, are often ineffective.
The key then seems to be to keep the life-saving properties of the acute inflammatory response without allowing it to become chronic. But how?
One clue came in 2000 when Serhan and his team revealed that inflammation has an off switch. Until then, the reaction was thought to peter out as the immune cells that secrete cytokines gradually reduced in number and their effects became diluted. In fact, Serhan found that neutrophils and macrophages, the types of white blood cell that kick off the process, actively change tack once it has got going, releasing a second set of chemicals — called resolvins — that help mop up any remaining cytokines and sweep away any debris.