Acupuncture may warrant systematic investigation as an adjunctive host-directed therapy in neuroinfectious diseases, where neurologic injury can be driven not only by pathogen burden but also by dysregulated host immune responses, according to a Perspective published in Frontiers in Medicine.
The article, written by Yun Jin Kim, PhD, of the College of Medicine and Health Sciences at United Arab Emirates University, proposed that acupuncture’s reported effects on neuroimmune signaling, blood-brain barrier (BBB) integrity, and oxidative stress align with key mechanisms underlying central nervous system infection-related injury. However, the author emphasized that existing evidence derives predominantly from noninfectious models and requires cautious interpretation.
Neuroinfectious diseases — including viral encephalitis, bacterial meningitis, sepsis-associated encephalopathy, and neuro-COVID — continue to cause substantial morbidity and mortality despite advances in antimicrobial therapy. Survivors frequently experience long-term neurologic sequelae, including cognitive impairment, epilepsy, and psychiatric disorders. The author noted that current host-directed approaches remain limited and largely rely on broad immunomodulatory therapies such as corticosteroids. Interventions including interferon-gamma immunotherapy in HIV-associated cryptococcal meningitis and interleukin-6 receptor blockade in COVID-19-associated hyperinflammatory encephalopathy have demonstrated growing interest in targeting host responses alongside pathogens.
Rather than presenting new experimental findings, the Perspective synthesized evidence from preclinical and clinical literature examining acupuncture’s effects on pathways implicated in neuroinflammation. Across multiple experimental models, electroacupuncture at acupoints including ST36 and GV20 was associated with suppression of Toll-like receptor 4, nuclear factor kappa B, and NLRP3 inflammasome signaling, accompanied by reductions in interleukin-1 beta, interleukin-6, tumor necrosis factor alpha, and microglial activation.
Among the most relevant, though still indirect, infection-related evidence reviewed were studies of sepsis-associated encephalopathy, a condition characterized by infection-driven neuroinflammation, BBB dysfunction, and cognitive impairment. In these models, electroacupuncture attenuated hippocampal neuroinflammation, reduced microglial activation, suppressed high-mobility group box 1/Toll-like receptor 4/nuclear factor kappa B signaling, and improved working memory performance. Additional studies reported increased acetylcholine and alpha-7 nicotinic acetylcholine receptor expression, alongside reductions in oxidative stress and inflammatory activity within the hippocampus.
The Perspective also highlighted preclinical evidence that electroacupuncture preserved BBB integrity by reducing high-mobility group box 1 release, lowering receptor for advanced glycation end products and Toll-like receptor 4 expression, and maintaining tight-junction proteins including occludin, claudin-5, and zonula occludens-1. A preclinical meta-analysis cited in the article reported reduced pathological BBB permeability across multiple models of brain injury, accompanied by reductions in inflammatory mediators and glial activation. These mechanisms may be relevant given the established role of BBB disruption in bacterial meningitis, viral encephalitis, and other neuroinfectious diseases.
Additional preclinical studies cited in the article linked acupuncture to activation of antioxidant pathways involving nuclear factor erythroid 2-related factor 2, heme oxygenase-1, and glutathione peroxidase 4 — the latter a key enzyme whose depletion can trigger ferroptosis, an iron-dependent form of regulated cell death. These pathways were associated with reduced reactive oxygen species production, inhibition of ferroptosis, preservation of mitochondrial function, and improved neurologic outcomes in experimental models.
The author cautioned that direct evidence supporting acupuncture in neuroinfectious diseases remains limited. Most available data come from noninfectious neurologic models or indirect infection-related models, limiting conclusions regarding clinical efficacy. Key gaps include heterogeneity in acupuncture protocols, uncertainty about how acupuncture-induced immunomodulation might affect pathogen clearance, the lack of standardized infection-specific models, and the need to define appropriate timing, safety, and biomarker endpoints.
The author was explicit that acupuncture should be viewed not as an established therapy for neuroinfectious diseases, but as a mechanistically plausible adjunctive strategy requiring rigorous infection-specific validation. Future investigations will require infection-specific animal models, standardized acupuncture protocols, biomarker-driven randomized controlled trials, and integration of advanced approaches such as neuroimaging, single-cell transcriptomics, and spatial profiling to determine whether the observed neuroimmune effects translate into meaningful clinical benefit.
Disclosures: The author reported no external funding, no commercial or financial conflicts of interest, and no generative artificial intelligence use in manuscript creation.
Source: Frontiers in Medicine
