The Systemic Inflammation Cascade describes the complex, widespread, and self-perpetuating sequence of biochemical events initiated by a chronic, low-grade inflammatory stimulus, often originating from excess visceral adipose tissue or gut dysbiosis, leading to the sustained release of pro-inflammatory cytokines like IL-6, TNF-alpha, and CRP into the general circulation. This persistent, non-resolving inflammatory state is a core pathological driver that directly impairs insulin signaling, accelerates cellular senescence, and disrupts the hypothalamic-pituitary-adrenal (HPA) axis, contributing significantly to metabolic and hormonal disease.
Origin
The term combines Systemic Inflammation, referring to inflammation affecting the entire body, with Cascade, denoting a chain of reactions. Its foundation is in immunology and metabolic research, recognizing that chronic inflammation is not merely a symptom but a central, active mechanism of disease. The concept is crucial in understanding the crosstalk between the immune system and the endocrine system.
Mechanism
The cascade is perpetuated by the activation of key inflammatory transcription factors, such as NF-κB, which upregulate the gene expression of pro-inflammatory cytokines in various tissues, including immune cells and adipocytes. These circulating cytokines then interfere with the insulin receptor signaling pathway, leading to insulin resistance, and they also contribute to hypothalamic dysfunction, thereby disrupting the finely tuned hormonal feedback loops. Breaking this cascade is a primary therapeutic target in longevity and metabolic health.
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