Histological Survey of the Effect of Granulocyte-colony-stimulating Factor(G-CSF) on Bacterial Translocation and Wound Healing in Burned Mice


1 Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran

2 Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases; Eye Research Center, The Five Senses Institute, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran

3 Department of Veterinary Medicine, Azad University, Abhar Branch, Abhar, Iran

4 Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

5 Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran


Background: Burn wound is an important cause of morbidity and mortality worldwide. Improving the host's immune system and removing the infection can be effective in healing wounds caused by burns. Granulocyte-colony-stimulating factor (G-CSF) stimulates both the bone marrow to produce granulocytes and the function of neutrophil precursors. The aim of this study was to examine the effect of G-CSF on removing infection and healing wound. Materials and Methods: A burn model was used to induce burns in 18 adult Balb/c mice, and their wounds were infected by Acinetobacter baumannii strains. Burned mice were divided into two groups (control and G-CSF) and treated daily by subcutaneous injections of normal saline (0.1 mL) and G-CSF (10 μg/kg). The wound healing process was evaluated by the morphological and histological assessments. Results: In morphological assay, the mean size of the wounds in the 3rd and 7th days of the treatment was significantly lower in the G-CSF treated group compared to the control group. Some of the histological parameters were evaluated, including the level of inflammation, re-epithelialization, angiogenesis, collagen deposition, the amount of granulation tissue, and fibroblast maturation. The results showed that inflammation was reduced in the G-CSF-treated group, and re-epithelialization and collagen deposition were increased insignificantly compared to the normal saline-treated group. Furthermore, bacterial translocation was reduced significantly in the G-CSF-treated group. Conclusion: G-CSF enhances wound closure and helps in wound healing by improving the immune system. It has also an anti-inflammatory role and reduces bacterial translocation.


1. Singh P, Harish D. Incidence of post burn septicemia at a tertiary care hospital. JIAFM Oct-Dec2011. 2011;33:319-23.
2. Agbenorku P, Aboah K, Akpaloo J, Amankwa R, Farhat B, Turkson E, et al. Epidemiological studies of burn patients in a burn center in Ghana: any clues for prevention? Burns & trauma. 2016;4:21. 
3. Deotare U, Al-Dawsari G, Couban S, Lipton J. G-CSF-primed bone marrow as a source of stem cells for allografting: revisiting the concept. Bone marrow transplantation. 2015;50:1150. 
4. Wiest R. Bacterial translocation. Bioscience and microflora. 2005;24:61-90. 5. Tekin R, Dal T, Bozkurt F, Deveci Ö, Palancı Y, Arslan E, et al. Risk factors for nosocomial burn wound infection caused by multidrug resistant Acinetobacter baumannii. Journal of Burn Care & Research. 2014;35:e73-e80. 6. Dasari H, Kumar A, Sharma B. Burns Septicemia–The Leading cause of burn mortality. Journal of Punjab Academy of Forensic Medicine & Toxicology. 2008;8:10-6. 
7. Harrison C. Innate immunity as a key element in host defense against methicillin resistant Staphylococcus aureus. Minerva pediatrica. 2009;61:503-14. 
8. Horiuchi T, Shimizu K, Sasaki K, Kato A, Homma Y. Granulocytecolony stimulating factor producing infiltrating urothelial carcinoma of the left renal pelvis: a case report. Urology case reports. 2017;10:11-3. 
9. Kramer GC, Lund T, Herndon D. Pathophysiology of burn shock and burn edema. In Total Burn Care (Herndon DN, 4th ed). 2012:103-13. 
10. Yalçin O, Soybir G, Köksoy F, Köse H, Öztürk R, Çokne B. Effects of granulocyte colony-stimulating factor on bacterial translocation due to burn wound sepsis. Surgery today. 1997;27:154-8. 
11. Chen CH, Sereti KI, Wu BM, Ardehali R. Translational aspects of cardiac cell therapy. Journal of cellular and molecular medicine. 2015;19:1757-72. 12. Lee M, Aoki M, Kondo T, Kobayashi K, Okumura K, Komori K, et al. Therapeutic angiogenesis with intramuscular injection of low-dose recombinant granulocyte-colony stimulating factor. Arteriosclerosis, thrombosis, and vascular biology. 2005;25:2535-41. 
13. Huang H, Zhang Q, Liu J, Hao H, Jiang C, Han W. Granulocyte-colony stimulating factor (G-CSF) accelerates wound healing in hemorrhagic shock rats by enhancing angiogenesis and attenuating apoptosis. Medical science monitor: international medical journal of experimental and clinical research. 2017;23:2644. 
14. Brubaker AL, Kovacs EJ. G-CSF enhances resolution of Staphylococcus aureus wound infection in an age-dependent manner. Shock (Augusta, Ga). 2013;40:327. 
15. Greenhalgh DG, Sprugel KH, Murray MJ, Ross R. PDGF and FGF stimulate wound healing in the genetically diabetic mouse. The American journal of pathology. 1990;136:1235. 
16. Eroglu E, Agalar F, Altuntas I, Eroglu F. Effects of granulocyte-colony stimulating factor on wound healing in a mouse model of burn trauma. The Tohoku journal of experimental medicine. 2004;204:11-6. 
17. Thompson MG, Black CC, Pavlicek RL, Honnold CL, Wise MC, Alamneh YA, et al. Validation of a novel murine wound model of Acinetobacter baumannii infection. Antimicrobial agents and chemotherapy. 2014;58:1332-42. 
18. Abramov Y, Golden B, Sullivan M, Botros SM, Miller JJR, Alshahrour A, et al. Histologic characterization of vaginal vs. abdominal surgical wound healing in a rabbit model. Wound repair and regeneration. 2007;15:80-6. 
19. Gardner JC, Noel JG, Nikolaidis NM, Karns R, Aronow BJ, Ogle CK, et al. G-CSF drives a posttraumatic immune program that protects the host from infection. The Journal of Immunology. 2014;192:2405-17. 
20. Cohen AM, Hines DK, Korach ES, Ratzkin BJ. In vivo activation of neutrophil function in hamsters by recombinant human granulocyte colony-stimulating factor. Infection and immunity. 1988;56:2861-5. 
21. Martins A, Han J, Kim SO. The multifaceted effects of granulocyte colony-stimulating factor in immunomodulation and potential roles in intestinal immune homeostasis. IUBMB life. 2010;62:611-7. 
22. Fine J-D, Manes B, Frangoul H. Systemic granulocyte colonystimulating factor (G-CSF) enhances wound healing in dystrophic epidermolysis bullosa (DEB): Results of a pilot trial. Journal of the American Academy of Dermatology. 2015;73:56-61. 
23. Roberts AW. G-CSF: a key regulator of neutrophil production, but that’s not all! Growth factors. 2005;23:33-41. 
24. Petit I, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L, et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF1 and up-regulating CXCR4. Nature immunology. 2002;3:687. 
25. Hartung T. Anti-inflammatory effects of granulocyte colony-stimulating factor. Current opinion in hematology. 1998;5:221-5. 
26. Liao M-F, Yeh S-R, Lo A-L, Chao P-K, Lee Y-L, Hung Y-H, et al. An early granulocyte colony-stimulating factor treatment attenuates neuropathic pain through activation of mu opioid receptors on the injured nerve. Scientific reports. 2016;6:25490. 
27. Wallner S, Peters S, Pitzer C, Resch H, Bogdahn U, Schneider A. The granulocyte-colony stimulating factor has a dual role in neuronal and vascular plasticity. Frontiers in cell and developmental biology. 2015;3:48. 
28. Sato D, Otani H, Fujita M, Shimazu T, Yoshioka K, Enoki C, et al. Granulocyte colony-stimulating factor does not enhance recruitment of bone marrow-derived cells in rats with acute myocardial infarction. Experimental & Clinical Cardiology. 2012;17:83. 
29. Tuo H-F, Peng Y-H, Bao L, Zhang W-X. Effects of Granulocyte ColonyStimulating Factor on Opsonin Receptor Expression and Neutrophil Antibacterial Activity in a Mouse Model of Severe Acute Pancreatitis. Advances in Hygiene & Experimental Medicine/Postepy Higieny i Medycyny Doswiadczalnej. 2017;71. 
30. Park S, Rich J, Hanses F, Lee JC. Defects in innate immunity predispose C57BL/6J-Leprdb/Leprdb mice to infection by Staphylococcus aureus. Infection and immunity. 2009;77:1008-14. 
31. Moghadam SS, Aghmiyuni ZF, Zaheri H, Arianpour N, Danaeifard MR, Roham M, et al. Comparative effects of granulocyte-colony stimulating factor and colistin-alone or in combination on burn wound healing in Acinetobacter baumannii infected mice. Iranian journal of microbiology. 2018;10:371. 
32. Martino M, Fedele R, Massara E, Recchia AG, Irrera G, Morabito F. Longterm safety of granulocyte colony-stimulating factor in normal donors: is it all clear? Expert opinion on biological therapy. 2012;12:609-21.