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Attend almost any medical appointment today and you’ll likely hear the word inflammation hovering in the background like a confusing puzzle piece that seems important even though it isn’t the focus of diagnosis or treatment. ‘You have some longer-term damage to your gut after the infection,’ a gastroenterologist explained to me recently, ‘the technical term is that you have inflammation.’

Enquire further, and it doesn’t get any easier to pin down. The year prior, another doctor, reading a pathology report, told me: ‘Good news – this biopsy isn’t endometriosis or cancer, it’s just non-specific chronic inflammation.’ When I asked what that meant, they suggested I check with the pathologist.

The pathologist, in turn, explained that she had simply classified the tissue according to the textbook. Simple – or oversimplified? Weren’t endometriosis and cancer also inflammatory conditions? Why did all these answers mean such different things? How did they know it was ‘chronic’ specifically? Did I need to get rid of it? Would the stress of worrying about all this make my inflammation worse? Is inflammation actually good in small doses, or a specific entity at all?

Unlike chronic inflammation, the kind of acute inflammation described in medical textbooks has a long and stable history. In Western medical culture, it has been understood as our essential healing response to injury or infection – ‘the body’s unique mechanism to maintain its integrity in response to macroscopic and microscopic injuries,’ as the health psychologist Jeanette Bennett and colleagues put it. From a sprained ankle to an infected cut, acute inflammation is the main reason our bodies respond and recover. It has classically been defined by five cardinal signs: redness, swelling, heat, pain, and loss of function. Advances in microscopy, cell biology, immunology and related fields have continued to refine this paradigm, with inflammation being described as the activation of immune and non-immune cells, inflammatory mediators, and systemic energy-saving responses following injury, infection or disease, affecting a range of body systems, sleep, appetite, and behaviour.

The five cardinal signs of inflammation, designed for the International Inflammation Club by D A Willoughby and W G Spector in the 1960s. The four original signs of inflammation (calor, rubor, tumor et dolor) were described by Celsus in the 1st century CE, and a fifth (function laesa) was added by Rudolf Virchow in 1871.

This acute version of inflammation, though often painful, is protective: swelling brings immune ‘defenders’ to the wound, heat makes the environment hostile to pathogens, and pain forces rest so the body can repair itself. Ancient civilisations treated such inflammation with plants containing what science now calls salicylates, compounds used in aspirin. Musculoskeletal specialists study how to optimise healing with temperature, pressure, behaviour change, and chemical therapies. Today, the global market for anti-inflammatory drugs amounts to hundreds of billions of dollars annually. That this explanation of acute inflammation makes intuitive sense both inside and outside medicine is testament to its longstanding cultural acceptance.

Is chronic inflammation a defence gone awry, or a misguided attempt by the body to heal itself?

The anomaly on the scene is chronic inflammation. Unlike the sharp, visible signs of acute inflammation, chronic inflammation is low grade – simmering quietly but occasionally flaring up dramatically – and it’s systemic, affecting the whole body rather than staying at the site of injury. It appears to accompany many chronic diseases, both as a cause and as a consequence. Chronic inflammation has different triggers, chronicity, severity, symptoms, and biomarkers than acute inflammation – so different that the two seem unrelated at first glance. What ties them together – and explains why both are called inflammation – is the same immune response: white blood cells spring into action, releasing cytokines that send chemical signals and alter tissues. In acute inflammation, this activity is so important for healing that some branches of medicine now actively discourage use of anti-inflammatory treatments. In chronic inflammation, the process never fully turns off, leaving a persistent, smouldering state that can gradually damage the body rather than repair it.

Chronic inflammation complicates the picture. It rarely shows the familiar signs of redness, swelling or heat, and may arise without clear cause – sometimes linked to infection or injury, but often not. Some researchers suggest it’s less a disease than a ‘physiological pathway through which environments early in life shape trajectories of health in adulthood.’ In this view, early exposure to stress, poor nutrition or pollution can tune the body’s immune responses for life – priming them to overreact or stay switched on even when no threat remains. Testing offers little certainty either: blood markers such as C-reactive protein (CRP) indicate when inflammation is present but not where or why, and readings can vary depending on the type of test, its sensitivity, and how results are interpreted. As the nutritional scientist A Catharine Ross notes, using the same word inflammation for both acute and chronic forms may obscure the distinct biological processes driving each.

Still, the consequences of chronic inflammation are profound. The list of conditions that can now be grouped under ‘chronic inflammatory diseases’ is strikingly long: obesity, asthma, heart disease, irritable bowel, Alzheimer’s, cancer, arthritis, chronic obstructive pulmonary disease, endometriosis, stroke, Type 2 diabetes, HIV/AIDS, fibromyalgia, and even some forms of depression and schizophrenia. Many of these illnesses are rising worldwide, amounting to ‘some of the most significant biomedical urgencies of our time’, as the immunologist Martin Trapecar puts it. When aggregated, chronic inflammatory conditions today represent ‘the most significant cause of death in the world’, in the words of the longevity researcher David Furman and colleagues.

Little wonder commentators now

© Aeon