Neuroimmune Crosstalk in Systemic Disease: An Interdisciplinary Perspective Between Neurology and Internal Medicine

Resumen

Neuroinflammation has emerged as a fundamental pathophysiological mechanism linking neurological disorders with systemic inflammatory diseases. Increasing evidence demonstrates that chronic immune activation contributes significantly to neuronal dysfunction, cognitive impairment, neurodegeneration, and multisystem clinical manifestations through complex interactions involving microglial activation, cytokine signaling, oxidative stress, endothelial dysfunction, mitochondrial injury, and blood–brain barrier disruption. The objective of this review was to analyze the role of neuroinflammation as an interdisciplinary bridge between neurology, immunology, and internal medicine while evaluating its clinical, molecular, and translational implications. A narrative review methodology based on the Scientific Method and Process-Based Methodology was employed. Scientific literature indexed in international databases including PubMed, Scopus, ScienceDirect, SpringerLink, and Frontiers was analyzed. The review prioritized peer-reviewed studies published primarily between 2020 and 2025 addressing neuroimmune communication, neurodegeneration, metabolic disorders, autoimmune diseases, infectious syndromes, and gut–brain axis interactions. The analyzed evidence demonstrated that neuroinflammatory mechanisms are strongly associated with metabolic diseases such as obesity and type 2 diabetes mellitus, autoimmune disorders including systemic lupus erythematosus, infectious conditions such as sepsis and long COVID syndrome, and neurodegenerative diseases. Persistent inflammatory activation was consistently related to cognitive impairment, chronic fatigue, depression, autonomic dysfunction, chronic pain, and progressive neuronal injury. Furthermore, the gut–brain axis emerged as a major regulator of neuroimmune communication, reinforcing the systemic nature of neuroinflammation.