Low-grade inflammation, also clinically termed chronic systemic inflammation, is a persistent, subclinical elevation of circulating pro-inflammatory mediators, such as C-reactive protein (CRP) and various cytokines, without the overt, localized signs of acute infection or injury. This subtle, continuous immune activation is a fundamental, non-infectious driver of numerous age-related chronic pathologies, including cardiovascular disease, insulin resistance, and neurodegenerative disorders. It represents a maladaptive, sustained activation of the innate immune system.
Origin
The concept emerged from the recognition that many chronic, non-communicable diseases share a common inflammatory basis, linking metabolic dysfunction directly to immune cell signaling. The term “low-grade” distinguishes this chronic, metabolically-driven state from the intense, short-lived response of classical acute inflammation. This paradigm shift placed chronic immune dysregulation at the center of the pathogenesis of many hormonal and metabolic diseases.
Mechanism
This chronic state is often triggered by factors like excessive visceral adiposity, gut barrier dysfunction, or chronic psychological stress. Adipose tissue, particularly, functions as an endocrine organ that releases pro-inflammatory cytokines, which interfere with the insulin signaling cascade in target tissues, thereby driving systemic insulin resistance. Concurrently, chronic HPA axis activation and subsequent cortisol dysregulation further impair the immune system’s ability to resolve inflammation, perpetuating the low-grade inflammatory cycle.
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