Neuroimmune Regulation of Chronic Inflammation: A Systems Perspective on Acupuncture

Abstract Chronic inflammation is a central pathological feature of many contemporary diseases, including autoimmune disorders, chronic pain syndromes, neuropsychiatric conditions, and postviral sequelae. Increasing evidence indicates that inflammatory dysregulation arises from disturbed interactions among immune, neural, and endocrine systems rather than from isolated molecular abnormalities. The objective of this study is to synthesize clinical and mechanistic evidence on acupuncture's role in modulating inflammation through neuroimmune regulatory pathways, with particular emphasis on cytokine balance and systems-level mechanisms. A narrative review of experimental studies, randomized controlled trials, meta-analyses, and mechanistic investigations examining acupuncture-induced modulation of cytokines, autonomic activity, neuroendocrine signaling, and immune cell phenotypes. Across diverse disease contexts, acupuncture is associated with reductions in proinflammatory cytokines, including IL-6, TNF-α, and IL-1β, alongside increases in anti-inflammatory mediators such as IL-10 and TGF-β. Mechanistic studies demonstrate that these effects are mediated through coordinated engagement of the vagal–cholinergic anti-inflammatory reflex, normalization of hypothalamic–pituitary–adrenal axis dynamics, immune cell reprogramming, and connective tissue mechanotransduction. Rather than producing global immunosuppression, acupuncture appears to recalibrate immune responsiveness in a context-dependent manner. Viewed through a neuroimmune systems framework, acupuncture functions as a biologically active immunomodulatory intervention capable of restoring inflammatory homeostasis across multiple regulatory domains. This perspective provides a coherent biological rationale for its clinical effects and supports its integration into contemporary approaches to chronic inflammatory disease.