Anti‑inflammatory effect of metformin against an experimental model of LPS‑induced cytokine storm
Dr Ibrahim Taher, Eman El‑masry, Mohamed Abouelkheir, Ahmed E Taha
Experimental and Therapeutic Medicine, doi:10.3892/etm.2023.12114
Cytokine storm is one of the leading causes of death in patients with COVID-19. Metformin has been shown to inhibit the action of a wide range of proinflammatory cytokines such as IL-6, and TNF-α which may ultimately affect cytokine storm due to Covid-19. The present study analyzed the anti-inflammatory effect of oral and intraperitoneal (IP) metformin administration routes in a mouse model of lipopolysaccharide (LPS)-induced cytokine storm. A total of 60 female BALB/c mice were randomly assigned to one of six groups: i) Control; ii) LPS model; iii) oral saline + LPS; iv) oral metformin + LPS; v) IP saline + LPS; and vi) IP metformin + LPS. Metformin or saline were administered to the mice for 30 days, after which an IP injection of 0.5 mg/kg LPS induced a cytokine storm in the five treatment groups. Mice were sacrificed and serum cytokine levels were measured. Pretreatment of mice with either oral or IP metformin significantly reduced the increase in IL-1, IL-6 and TNF-α following LPS injection. Both metformin administration routes significantly reduced IL-1 and TNF-α levels, although IP metformin appeared to be significantly more effective at reducing IL-6 levels compared with oral metformin. Neither the oral or IP route of administration of metformin demonstrated a significant effect on IL-17 levels. Based on its ability to suppress the proinflammatory LPS-induced cytokine storm, metformin may have future potential benefits in ameliorating human diseases caused by elevated cytokine levels.
Authors' contributions All of the authors have made substantial contributions towards the completion of the present study. MA and AET conceived the present study, performed the experiments, were project administrators and prepared the draft manuscript. IAT, EAEM, MA and AET collected the data, obtained resources, performed data analysis and critically reviewed and edited the manuscript. IAT and EAEM acquired funding. IAT, MA and AET supervised the project. IAT and AET confirm the authenticity of the raw data. All authors read and approved the final version of the manuscript.
Ethics approval and consent to participate Ethical approval was obtained from the Local Committee of Bioethics of Jouf University (approval no. 07-08-42; Sakaka, Saudi Arabia).
Patient consent for publication Not applicable.
Competing interests The authors declare that they have no competing interests.
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