Inflammation and health

Mike Gleeson
13 minutes ago
6 min read

Inflammation has long been portrayed as something inherently bad; a process that needs to be fought or suppressed. In popular media, it’s associated with pain, chronic disease, and poor health. Yet, within the body, inflammation is also an essential initial component of the immune response. Inflammation is a tightly regulated system that evolved to protect us from infection and promote healing. The problem is not inflammation itself, but when this finely tuned biological mechanism becomes dysregulated and persistent. Understanding when inflammation is beneficial and when it becomes harmful is fundamental not only to medicine but also to exercise science and performance nutrition.

Inflammation is a normal physiological response

The body’s inflammatory response is part of a highly orchestrated defence mechanism designed to recognise injury or infection and initiate repair. When tissues are damaged, say through trauma, infection, or intense exercise, local immune cells release chemical mediators such as histamine, prostaglandins, and cytokines. These substances increase blood flow to the affected tissue, allowing immune cells to access the site of injury. This local response, known as acute inflammation, is the redness, heat, swelling, and soreness familiar to anyone who has suffered a muscle strain or infection. It is a short-term, self-limiting process that enables the removal of pathogens and debris while setting the stage for tissue regeneration. Without inflammation, healing would not occur.

Chronic low-grade inflammation

However, when inflammation fails to resolve, or when the stimuli that provoke it are persistent, the process becomes maladaptive. Chronic low-grade inflammation represents a state in which the immune system is continually activated, but at a low level that is often imperceptible. It may persist for years, quietly damaging cells, tissues, and organs. Unlike acute inflammation, which is a necessary and protective event, chronic inflammation is now recognised as a key feature in the pathophysiology of many non-communicable diseases, including cardiovascular disease, type 2 diabetes, certain cancers, arthritis, and neurodegenerative disorders.

The prevalence of chronic low-grade inflammation in modern society is alarmingly high. Estimates suggest that more than half of adults exhibit elevated inflammatory biomarkers, even in the absence of overt disease. This persistent immune activation is closely linked to excess adiposity, particularly the accumulation of visceral fat, which is the metabolically active fat stored deep within the abdominal cavity. Adipose tissue was once thought to be merely an inert energy reservoir, but research over the last two decades has revealed that it acts as an endocrine organ, secreting numerous hormones and cytokines that influence metabolism, immune function, and inflammation. When fat cells (adipocytes) enlarge due to chronic energy surplus, they become stressed and begin to release signals that attract immune cells, especially macrophages, into the tissue. These macrophages shift from an anti-inflammatory (M2) to a pro-inflammatory (M1) phenotype, releasing cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6).

This process transforms adipose tissue from a benign energy store into a source of chronic inflammatory signals that can spread systemically. The resulting “metaflammation” — metabolic inflammation — interferes with insulin signalling, promotes endothelial dysfunction, and contributes to atherosclerosis. Elevated levels of circulating inflammatory biomarkers such as C-reactive protein (CRP), TNF-α, and IL-6 are predictive of future cardiovascular events and metabolic disease. Importantly, this form of inflammation is largely silent: there is no pain, no swelling, no fever. It progresses quietly but steadily, eroding metabolic health over time.

The consequences of chronic inflammation for health

The consequences of chronic inflammation extend beyond metabolism. Chronic inflammation alters immune regulation, leading to exaggerated or inappropriate responses to infection. This became tragically evident during the COVID-19 pandemic, when individuals with obesity and metabolic syndrome were more likely to develop severe inflammatory complications such as acute respiratory distress syndrome. The combination of a pro-inflammatory baseline state and an over-reactive immune system created a “perfect storm” of dysregulated inflammation. In essence, the same process that evolved to protect the body was now contributing to its injury.

The anti-inflammatory effects of exercise

So what can be done to counter this chronic inflammatory load? The answer, supported by decades of research, is exercise. Regular physical activity is one of the most potent anti-inflammatory strategies available. These benefits are not necessarily through suppression of the immune system, but by restoring balance within it. The evidence for this is compelling. A recent meta-analysis encompassing 25 systematic reviews concluded that structured exercise interventions consistently reduce systemic inflammation, as reflected by lower circulating levels of CRP, IL-6, and TNF-α. These effects are seen across various populations, from individuals with metabolic disease to healthy but sedentary overweight adults.

Connections between exercise, diet, obesity and inflammation

The anti-inflammatory actions of exercise are mediated through several interconnected mechanisms. First, regular exercise reduces visceral fat mass by increasing energy expenditure and enhancing fat oxidation. This alone attenuates the production of pro-inflammatory signals. Second, exercise influences immune cell behaviour directly. Within adipose tissue, it promotes a shift from M1 to M2 macrophages, restoring an anti-inflammatory environment. At the systemic level, exercise modulates the expression of genes involved in inflammation: after an exercise bout, circulating immune cells show upregulation of anti-inflammatory genes and downregulation of pro-inflammatory ones, even when challenged with bacterial components in vitro.

Skeletal muscle as an endocrine organ

Perhaps most fascinating is the role of skeletal muscle as an endocrine organ. Contracting muscles release signalling molecules known as myokines, which communicate with distant tissues and organs. Among these, interleukin-6 (IL-6) plays a central role. Unlike the IL-6 released from immune cells during infection, which contributes to a pro-inflammatory cascade, muscle-derived IL-6 acts in an anti-inflammatory and metabolic regulatory capacity. It is produced in proportion to exercise intensity and duration, particularly as muscle glycogen stores decline. Once released, it stimulates fat oxidation and glucose mobilisation from the liver, ensuring fuel availability for working muscles. Simultaneously, IL-6 induces the production of anti-inflammatory cytokines such as IL-10 and IL-1 receptor antagonist (IL-1ra), while suppressing TNF-α. It also triggers the release of cortisol through the hypothalamic–pituitary–adrenal axis, providing further immunoregulatory control.

This elegant physiological response contrasts sharply with the cytokine profile seen in sepsis or infection, where IL-6 follows a surge of pro-inflammatory mediators. During exercise, IL-6 acts as a metabolic messenger and an anti-inflammatory signal — a biological demonstration of why exercise truly functions as medicine.

The influence of exercise on inflammation extends beyond cytokines. Regular physical activity downregulates Toll-like receptors (TLRs) on immune cells, reducing their sensitivity to inflammatory stimuli such as bacterial endotoxins. This “dampening” of acquired immune activation contributes to lower baseline inflammation without compromising immune defence. In other words, exercise recalibrates the system: ready to respond when needed, but not perpetually activated.

The anti-inflammatory effects of diet

While exercise exerts a profound influence on inflammation, it does not act in isolation. Diet is an equally powerful modulator. The modern Western dietary pattern — rich in refined carbohydrates, processed meats, saturated fats, and added sugars — promotes weight gain and amplifies inflammatory processes. Conversely, dietary patterns such as the Mediterranean diet and DASH diet are consistently associated with lower inflammatory biomarkers and reduced incidence of cardiovascular disease. These diets share key characteristics: a high intake of fruits, vegetables, legumes, whole grains, nuts, and oily fish, and the use of olive oil as a principal fat source. The common denominator is nutrient density, fibre, antioxidants and the predominance of unsaturated fats, particularly omega-3 fatty acids, which exert well-documented anti-inflammatory effects through modulation of eicosanoid pathways and cell membrane composition.

Combined effects of exercise and diet on inflammation and health

Recent analyses using data from the U.S. National Health and Nutrition Examination Survey (NHANES) illustrate the synergy between diet and physical activity. Individuals adhering to an anti-inflammatory dietary pattern who also engaged in regular vigorous exercise had significantly less visceral and subcutaneous adipose tissue. The relationship between vigorous activity and fat reduction followed an L-shaped curve: the largest benefit occurred when people moved from near inactivity to around 75 minutes per week of vigorous activity — a relatively modest but physiologically meaningful threshold. Beyond this, further benefits accrued at a slower rate, reinforcing the message that doing something is vastly better than doing nothing.

Together, these findings underscore a central theme: chronic low-grade inflammation is not an inevitable consequence of aging or modern life. It is a modifiable condition — one that responds profoundly to behavioural change. By combining regular physical activity with a nutrient-rich, anti-inflammatory diet, we can alter the trajectory of health and performance. These lifestyle factors act through converging biological mechanisms: reducing visceral fat, modulating cytokine networks, improving mitochondrial efficiency, and restoring immune balance.

Summary

The takeaway is clear. Inflammation is neither wholly good nor bad. It is a necessary process that, when properly regulated, protects and heals. Yet when the system is chronically activated, for example through excess energy intake, inactivity, and poor diet, inflammation becomes the driver of disease rather than the remedy. The scientific evidence now leaves little doubt that exercise and diet are not merely complementary tools but powerful therapeutic agents capable of reshaping inflammatory physiology. Managing inflammation is not about suppression; it is about balance, and the choices we make each day determine on which side of that balance we live.