Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 06 1 13 EN Rahimeh Mohseni Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Sara Soudi Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Arezou Rahimi Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Majid Sadeghizadeh Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran Arezou Khosrojerdi Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran 2025 08 11 2025 12 28 Sepsis is a life-threatening condition characterized by a dysregulated immune response leading to organ failure. This study examines the immunomodulatory effects of the M13 bacteriophage in a cecal ligation and puncture (CLP) mouse model of sepsis, comparing intravenous and intraperitoneal delivery routes. Key outcomes included cytokine responses, bacterial burden, organ injury, and survival. Sepsis was induced using the CLP model. M13 phages were verified by transmission electron microscopy and administered via IV or IP injection. Blood samples were collected at 24 hours, 72 hours, and day 5 for white blood cell, cytokine, and liver enzyme analysis. Bacterial burden was assessed by colony counts, liver injury by hematoxylin and eosin histology, and survival was monitored for 14 days. CLP induction caused marked increases in WBC counts, cytokines, C-reactive protein (CRP), bacterial load, and liver damage. Following phage treatment, inflammatory markers, bacterial burden, and tissue injury declined substantially. IV administration more effectively reduced systemic inflammation, whereas IP administration provided stronger protection of liver and kidney function and resulted in higher survival rates. M13 phage therapy demonstrates promising immunomodulatory and organ-protective effects in septic mice. The superior organ protection and survival benefits observed with IP delivery suggest potential translational value for targeted phage administration in sepsis management. Future studies should explore dose optimization, combination therapy, and mechanistic pathways to support clinical development. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4543 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4543/2335