Low-grade Chronic Inflammation as a Common Pathway for Chronic Diseases: A Review from a Public Health Perspective

Low-grade chronic inflammation is increasingly invoked as a shared biological pathway linking diverse chronic diseases, yet the phrase often compresses distinct tissue processes, biomarkers and causal relationships into a single explanatory label. This critical narrative review evaluates when chronic systemic inflammatory activity functions as a mechanistic contributor, when it is primarily a marker of disease burden, and when disease-specific pathways limit the usefulness of a unifying model. Literature published from 1 January 1990 to 31 May 2026 was selected through searches of PubMed/MEDLINE and OpenAlex, supplemented by citation tracing and bibliographic verification against authoritative records. Evidence was appraised across experimental studies, longitudinal cohorts, genetic analyses, systematic reviews and outcome-driven clinical trials. The strongest support for a causal inflammatory pathway occurs in atherosclerotic cardiovascular disease, where interleukin-1/interleukin-6 signalling, clonal haematopoiesis and randomised anti-inflammatory trials converge. In obesity, type 2 diabetes and metabolic dysfunction-associated steatotic liver disease, nutrient excess, adipose immune remodelling, inflammasome activation and impaired resolution form reciprocal loops with insulin resistance and tissue injury. In chronic kidney disease, cancer and neurodegeneration, inflammation is biologically important but more context-dependent, frequently acting as both cause and consequence. Ageing, senescent-cell secretomes, trained immunity, gut-barrier disturbance, sleep loss and psychosocial adversity can amplify inflammatory tone across organ systems. Nevertheless, single measurements of C-reactive protein or interleukin-6 are temporally variable, biologically non-specific and insufficient to identify the relevant tissue source or therapeutic target. Lifestyle interventions can reduce inflammatory biomarkers, but biomarker improvement does not automatically establish reduced clinical risk. Broad immunosuppression is therefore an unsuitable population strategy; benefit depends on disease stage, pathway selection and baseline inflammatory risk. A defensible common-pathway model treats low-grade inflammation as a network amplifier within multimorbidity rather than a universal initiating cause. Progress requires repeated and tissue-informed phenotyping, causal triangulation, diverse longitudinal cohorts and trials that connect pathway modulation to patient-important outcomes.