Inflammation

Although intermittent increases in inflammation are critical for survival during physical injury and infection, certain social, environmental and lifestyle factors can promote systemic chronic inflammation that can lead to several diseases representing the leading causes of disability and mortality worldwide. ^[1] Chronic low-grade inflammation is now recognized as important in the pathology of numerous age-related chronic conditions, in which an unresolved inflammatory response is likely involved from the early stages of disease development. ^[2]

Systemic chronic inflammation is promoted by risk factors including infections, physical inactivity, poor diet, environmental and industrial toxicants, and psychological stress. ^[1] Microvascular endothelial cells at a site of inflammation are both active participants in and regulators of inflammatory processes, and their properties change during the transition from acute to chronic inflammation and from innate to adaptive immunity. ^[3] Macrophages are dynamic cells that play critical roles in the induction and resolution of sterile inflammation, and they can undergo M1 classical or M2 alternative polarized activation in response to signals such as interferons, Toll-like receptor engagement, or IL-4/IL-13. ^{[4] [5]}

Chronic inflammation is one of the twelve proposed hallmarks of aging, which are interconnected among each other and jointly drive the aging process. ^[6] Cellular senescence promotes chronic inflammation, and the senescence response is thought to drive both the degenerative and hyperplastic pathologies of aging largely through this mechanism. ^[7]

The evidence linking inflammation with atherosclerotic cardiovascular disease is described as compelling and clinically actionable, and residual inflammation measured with high-sensitivity C-reactive protein remains strongly predictive of recurrent events even in statin-treated patients. ^[8] Not all trials of anti-inflammatory therapy in secondary prevention have been successful, so such trial evidence is needed before broad recommendations for other agents can be made. ^[8] Because macrophages promote the re-balancing of pro-inflammatory responses towards pro-resolution responses, targeting regulators of macrophage plasticity is being pursued as a therapeutic strategy in inflammatory diseases. ^[4]