Chronic Inflammation as an Underlying Pathogenetic Mechanism of Chronic Non-Communicable Diseases: Molecular, Cellular, and Therapeutic Dimensions

Chronic non-communicable diseases (NCDs) constitute the leading cause of global morbidity and mortality. Over recent decades, chronic inflammation has been increasingly recognized not merely as an epiphenomenon of distinct clinical entities, but rather as an overarching pathogenetic mechanism uniting neurodegenerative, metabolic, oncological, autoimmune, allergic, and age-related disorders. This underscores the imperative for a comprehensive analysis across its molecular, cellular, and therapeutic facets. Consequently, this review aims to map and synthesize contemporary data concerning molecular pathways, cellular effectors, and therapeutic modalities for the modulation of chronic inflammation through a literature-based approach. A narrative review of the scientific literature – encompassing experimental, clinical, and review studies – was conducted to elucidate the role of inflammation in the pathogenesis of chronic diseases. The findings establish chronic inflammation as a universal pathogenetic mechanism underlying various chronic non-communicable diseases. Its molecular architecture encompasses the NF-κB, JAK-STAT, MAPK, PI3K/Akt/mTOR, HIF-1α, and AMPK/SIRT1/PPARγ signaling pathways, the NLRP3 inflammasome, and a complex cytokine network (TNF-α, IL-1β, IL-6, IL-17, IL-18, IL-33, TGF-β, and IL-10). Key cellular effectors span immune populations – including macrophages, neutrophils, dendritic cells, natural killer (NK) cells, T and B lymphocytes, and group 2 innate lymphoid cells (ILC2s) – as well as non-immune and parenchymal cell lineages, such as adipocytes, hepatocytes, myocytes, fibroblasts, and senescent cells, all demonstrating marked phenotypic plasticity. Therapeutic modalities – spanning anti-cytokine agents, NLRP3 inflammasome inhibitors, Janus kinase (JAK) inhibitors, metabolic modulators, antioxidants, natural phytochemicals, microbiome-directed therapies, senolytics, and targeted delivery platforms – exhibit substantial promise, yet demand a precision medicine framework owing to the context-dependent, pleiotropic nature of specific mediators and the inherent heterogeneity of inflammatory phenotypes. Chronic inflammation represents a pivotal pathogenetic driver underlying various chronic non-communicable diseases. Its molecular and cellular components form an integrated, highly dynamic network, offering a viable and high-value target for therapeutic intervention. High-priority research directions encompass multi-omics studies, the discovery and validation of robust inflammatory biomarkers, and the formulation of personalized and combinatorial therapeutic frameworks.