Neuro-Endocrine-Immune Crosstalk in Chronic Diseases: An Integrative Review of Molecular Mechanisms, Biomarkers, and Preventive Strategies

Background: The growing burden of chronic non-communicable diseases has highlighted the importance of the neuro-endocrine-immune (NEI) axis as a central regulatory network integrating neural, endocrine, and immune signaling to maintain physiological homeostasis and coordinate adaptive responses to internal and environmental challenges. Increasing evidence indicates that disruption of this bidirectional communication contributes to chronic low-grade inflammation, impaired stress adaptation, and the development of multiple chronic diseases. Objective: This integrative review aims to synthesize current evidence on the molecular mechanisms, regulatory networks, biomarkers, and translational implications of neuro-endocrine-immune crosstalk, with particular emphasis on its relevance for preventive strategies and personalized medicine. Materials and Methods: An integrative review of peer-reviewed literature indexed in PubMed, Scopus, and Web of Science was conducted. The available evidence was synthesized to identify key molecular pathways, neuroimmune regulatory mechanisms, environmental sensing pathways, and clinically relevant biomarkers associated with neuro-endocrine-immune (NEI) dysregulation. Results: The available evidence indicates that disruption of NEI crosstalk promotes persistent inflammatory activation, autonomic imbalance, impaired glucocorticoid signaling, and immune dysregulation, thereby contributing to the initiation and progression of major chronic diseases. Inflammatory mediators, cortisol dynamics, autonomic indices, microbiota-derived metabolites, and environmental sensing pathways have emerged as promising biomarkers and therapeutic targets for disease prevention and risk stratification. Conclusions: The NEI axis represents a fundamental systems-level interface linking environmental exposures, stress responses, and chronic disease development. A deeper understanding of NEI crosstalk provides a scientific basis for identifying clinically relevant biomarkers and supports the development of predictive, preventive, personalized, and participatory strategies for chronic disease prevention and management.