The biologic cascade of events that form the body's natural defenses against injury or infection is a vital part of the immune system. Ordinarily, this process is an acute response resulting in rapid, major increases in inflammatory mediators released into the circulation.1,2
In healthy, lean, non-elderly people, for example, blood concentrations of the acute-phase reactant C-reactive protein (CRP), which are normally less than 2 mg/L in men3
and less than 2.5 mg/ L in women,4
can increase more than 1000-fold in response to infection or trauma.2,5,6
Typically, a CRP value of 10 mg/L or more is considered indicative of clinically significant inflammation.7
However, recent evidence indicates that persistent elevations in circulating markers of inflammation, even when within the clinically normal range, are risk factors for cardiovascular disease in both middle-aged8,9,10,11,12,13
people. Recently, the US Centers for Disease Control and Prevention and the American Heart Association have stated that people with CRP values in the upper tertile of the adult population (> 3.0 mg/L) have a risk of cardiovascular disease that is double that of people whose CRP concentrations are less than 1.0 mg/L.20
In addition to CRP, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), along with several other acute-phase reactant proteins, cytokines and cytokine-soluble receptors, are strongly associated with increased risk for several chronic diseases, including cardiovascular disease,12,17,21,22
IL-6 and TNF-α are both stimulators of CRP release from hepatocytes.27,28
It is not yet known which of these factors might be the most robust indicator of underlying inflammation, or whether the effects of these biomarkers are additive for risk prediction.
As illustrated in , behavioural factors are associated with chronic, low-grade states of inflammation (as measured by slightly elevated inflammatory biomarkers), and therefore with the several chronic diseases that are associated with inflammatory states. Since the risk estimates associated with elevated inflammation appear to be linear (e.g., the CRP category cut-offs for assessment of cardiovascular disease risk20
are low risk < 1.0 mg/L, medium risk 1.0–3.0 mg/L and high risk > 3.0 mg/L), behavioural interventions that produce even slight reductions in inflammation may have clinically significant benefits. A few pharmacologic interventions such as use of angiotensin-converting-enzyme inhibitors and statins decrease inflammation, as evidenced by lowered CRP concentrations in prospective clinical trials.29,30,31,32
Moreover, there are very promising data suggesting that decreasing body weight and increasing physical activity are just as effective as medication for reducing overall inflammation. The published effects of behavioural interventions involving weight loss and exercise training on inflammatory markers are reviewed here.
Fig. 1: Reported behavioural factors associated with chronic subclinical inflammation, and diseases and adverse health conditions for which inflammation is a risk factor. ↓ = decreased; BMI = body mass index.