Cytokine Networks in Alcohol Use Disorder: A Narrative Review Highlighting Research Gaps and Future Priorities.

Background/Objectives: Alcohol Use Disorder (AUD) represents a significant global public health challenge that is associated with cognitive deficits, immune dysfunction, and increased susceptibility to different comorbidities. Recent evidence suggests that neuroimmune signalling, particularly microglial activation and cytokine-mediated pathways, plays a critical role in the development, persistence, and relapse vulnerability of AUD. This narrative review aims to synthesize current evidence on the role of cytokines and interleukins (ILs) in AUD, emphasizing their modulation during alcohol exposure, withdrawal, and abstinence. Methods: A comprehensive narrative review methodology was employed, including a search in PubMed, Scopus, and Web of Science using relevant keywords. Peer-reviewed studies published in English that examined cytokine and interleukin profiles in adults with AUD were included. The main findings were synthesized into thematic domains to identify recurring patterns, inconsistencies, and research gaps. Results: AUD is associated with significant alterations in cytokine profiles. Pro-inflammatory markers such as IL-1β, IL-6, tumour necrosis factor alpha (TNF-α), IL-8, and IL-18 are elevated during active alcohol use and early abstinence, while anti-inflammatory markers like IL-10 show fluctuations. These immune changes are linked to systemic inflammation, neurotoxicity, and AUD severity. Cytokine levels tend to normalize with sustained abstinence, although severe AUD may lead to prolonged immune dysregulation. Associations between inflammatory markers and psychiatric symptoms, including anxiety and depression, were also observed. Conclusions: Immune dysregulation plays a central role in AUD pathophysiology, with cytokines serving as potential biomarkers for disease progression and treatment response. Future research should focus on longitudinal studies, diverse patient populations, and mechanistic investigations to refine biomarker utility and develop targeted immunomodulatory therapies. Addressing inflammation and neuroplasticity may enhance clinical outcomes in AUD management.