Immunomodulatory Effects of Acupuncture on Inflammatory Markers in Patients with Musculoskeletal Pain: A Systematic Review of Randomized Controlled Trials

Background: Musculoskeletal pain remains a major cause of disability worldwide, encompassing disorders such as rheumatoid arthritis (RA), osteoarthritis (OA) and chronic back pain. Acupuncture and dry needling are increasingly used for symptom management, yet their effects on inflammatory modulation remain unclear. This systematic review and meta-analysis evaluated the influence of acupuncture on inflammatory biomarker regulation in musculoskeletal pain. Methods: Following PRISMA and Cochrane methodological guidelines, comprehensive searches were conducted across MEDLINE (via PubMed), Web of Science, Cochrane Library, Scopus, Google Scholar, and OpenEvidence from inception to August 2025. Eligible studies were randomized controlled trials (RCTs) involving acupuncture or dry needling interventions with inflammatory biomarker outcomes. Screening, data extraction, and risk of bias assessment using ROB2 were performed by two reviewers independently. The certainty of evidence was appraised using GRADE criteria. The protocol was registered on PROSPERO (CRD420251011831). Results: Nineteen RCTs and one randomized cross-over study (n = 1492) met inclusion criteria. Some studies demonstrated reductions in CRP, ESR, IL-1β, IL-6 and TNF-α following acupuncture. Random-effects meta-analysis indicated that modified acupuncture (electroacupuncture or needle-knife therapy) significantly reduced TNF-α in knee OA compared with traditional acupuncture (SMD = −1.63, 95% CI −2.47 to −0.80, p < 0.01) but not IL-1β. However, no significant effects were observed from acupuncture versus sham acupuncture for CRP or ESR in patients with arthritis. However, the findings are limited by high heterogeneity and the small number of studies included in each meta-analysis. Conclusions: A moderate level of GRADE evidence suggests that modified acupuncture may be more effective than standard acupuncture in reducing TNF-α levels in patients with OA. Further high-quality biomarker-based RCTs are warranted to confirm these findings. This study received no external funding.