In mice with severe infection, adding electroacupuncture at a specific back point to antibiotics helped them survive longer, reduced inflammation, and lowered stress‑hormone activity in the brain. The benefit came from turning down CRH‑producing neurons and turning up oxytocin‑producing neurons in a brain region that controls stress, which also raised adrenaline‑type chemicals that help control inflammation.

Sepsis, a life-threatening condition caused by a dysregulated host response to infection, continues to be a major cause of mortality in critical care despite medical advancements. This study aimed to investigate the therapeutic effects and neuroimmune mechanisms of electroacupuncture (EA) at the Shenshu (BL23) acupoint combined with antibiotic therapy in sepsis management. A cecal ligation and puncture (CLP)-induced murine sepsis model was used to evaluate the combined therapy. The study employed enzyme-linked immunosorbent assays (ELISA) and histological analysis to assess systemic inflammation and intestinal damage. Three-dimensional immunolabeling of c-Fos neurons and chemogenetic modulation of hypothalamic paraventricular nucleus (PVN) neurons were performed to investigate neural mechanisms. Additionally, serum catecholamine levels were measured using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The combination of EA and antibiotics significantly improved survival rates and reduced sepsis-induced weight loss. The therapy lowered systemic levels of proinflammatory cytokines (TNF-α and IL-6) and mitigated intestinal inflammatory infiltration. EA at BL23 suppressed neuronal activation in the PVN by reducing c-Fos expression. Chemogenetic inhibition of corticotropin-releasing hormone (CRH) neurons replicated the anti-inflammatory effects of the therapy, while their activation diminished therapeutic benefits. Conversely, activation of oxytocin (OXT) neurons reproduced the anti-inflammatory effects, and their inhibition reversed these benefits. The combined therapy also elevated serum catecholamine levels, indicating sympathetic-mediated immunomodulation. This study demonstrates that EA at BL23 enhances antibiotic efficacy in sepsis by modulating PVN activity-suppressing CRH neurons and activating OXT neurons-leading to increased catecholamine secretion and systemic inflammation control. These findings reveal a novel neuroimmunological pathway for acupuncture's therapeutic role in sepsis, supporting its potential as a noninvasive adjunctive therapy in critical care.