Operationalizing Chronic Inflammation: An Endotype-to-Care Framework for Precision and Equity.

Area of Science:

• Immunology
• Metabolic Science
• Systems Biology

Background:

• Chronic inflammation involves complex immune-metabolic circuits: pattern-recognition signaling, inflammasome activation, cytokine networks, immunometabolic reprogramming, barrier-microbiome disruption, cellular senescence, and neuro-immune-endocrine crosstalk.
• These interconnected axes drive various diseases, necessitating a unified understanding.

Purpose of the Study:

• To synthesize mechanistic insights into chronic inflammation across diseases.
• To introduce an operational endotype-to-care framework for precision-based, scalable, and equitable interventions.

Main Methods:

• A narrative, mechanism-focused review of recent literature on immune-metabolic circuits.
• Integration of pattern-recognition receptors, inflammasome pathways, cytokine modules, metabolic reprogramming, barrier-microbiome dynamics, senescence, and neuro-immune-endocrine signaling.
• Mapping low-cost screening biomarkers (hs-CRP, NLR, fibrinogen) to phenotype-guided endotyping panels and therapeutic modules with monitoring targets.

Main Results:

• A stepwise pathway from broad inflammatory screening to phenotype-specific endotyping (e.g., IL-6/TNF for metaflammation, ISG/IFN for autoimmunity).
• Paired targeted interventions with prespecified treat-to-target outcomes (e.g., ~40% hs-CRP reduction in 8-12 weeks).
• A tiered implementation model (essential, expanded, comprehensive) for adaptability and equity across clinical settings.

Conclusions:

• This framework operationalizes chronic inflammation management with numeric triage thresholds, minimal endotype panels, and objective monitoring criteria.
• It embeds principles of precision, equity, and stewardship for iterative, evidence-driven implementation.
• Enables real-world application of mechanistic insights for improved patient care.