Shahed University Immunoregulation 2588_5200 7 1 2024 03 01 Effect of Melatonin on Interleukin-6 and Inflammatory Markers in Premature Infants With Documented Sepsis: A Pilot Study 4942 10.32598/Immunoregulation.7.14 EN Reza Saeidi Neonatal Health Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Maryam Veysizadeh Pediatric Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran. Elnaz Nobakht Mofid Childern’s Hospital, Tehran, Iran. Parinaz Alizadeh Neonatal Health Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Farnosh Keshavarzi Neonatal Intensive Care Unit, Mofid Childern’s Hospital, Tehran, Iran. Mohammad Kordkatouli Department of Genetics, Faculty of Advanced Sciences and Technology, TeMS.C, Islamic Azad University, Tehran, Iran. 0009-0006-3008-6820 Journal Article 2025 09 08 <strong>Background</strong>: Premature neonates with documented sepsis who undergo surgery face heightened systemic inflammation, crucially mediated by interleukin-6 (IL-6). Given their low endogenous melatonin levels and melatonin’s known anti-inflammatory properties, this study aimed to evaluate the impact of adjunctive melatonin on IL-6 and other inflammatory markers in premature neonates with positive blood cultures or documented sepsis undergoing surgery.<br /><strong>Materials and Methods</strong>: This randomized controlled pilot study at Mofid Children’s Hospital (2023-2024) included 9 preterm neonates with positive blood cultures who were scheduled for surgery. They were randomized to receive either melatonin (0.1 mg/kg/day, n=6) or a placebo (n=3) orally for three days (pre- to post-surgery). Blood samples at baseline (T0) and two days post-surgery (T1) were collected to assess serum IL-6 and C-reactive protein (CRP) levels and white blood cell (WBC) counts. Repeat blood cultures were also performed. Data were analyzed using SPSS software, version 26 at a significance level of P<0.05. <br /><strong>Results</strong>: Baseline (T0) characteristics were comparable. Post-intervention (T1), the melatonin group showed significant reductions in CRP levels (T0: 9.333±7.828 mg/dL vs T1: 2.167±0.831 mg/dL; P=0.027) and WBC counts (T0: 13.933±3.741×103/μL vs T1: 9.933±2.196 ×103/μL; P=0.027), while the placebo group showed no significant changes. Although IL-6 decreased in both groups, it did not reach statistical significance. All melatonin-treated neonates achieved negative blood cultures, compared to 33% in the placebo group. <br /><strong>Conclusion</strong>: The use of adjunctive melatonin in preterm neonates with documented sepsis undergoing surgery suggests a reduction in systemic inflammation (CRP, WBC) and lower bloodstream infection rates. While the reduction in IL-6 was not statistically significant, these findings indicate melatonin’s potential as a safe and effective adjunctive therapy; however, further large-scale studies are warranted.  https://immunoreg.shahed.ac.ir/article_4942_31bd51a7403b980bf1039518120712e0.pdf