Taher Ibrahim, El-Masry Eman, Abouelkheir Mohamed, Taha Ahmed E
Microbiology and Immunology Unit, Department of Pathology, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia.
Department of Medical Microbiology and Immunology, College of Medicine, Menoufia University, Shebin El Koum 32511, Egypt.
Exp Ther Med. 2023 Jul 13;26(3):415. doi: 10.3892/etm.2023.12114. eCollection 2023 Sep.
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.
细胞因子风暴是新冠肺炎患者死亡的主要原因之一。二甲双胍已被证明能抑制多种促炎细胞因子的作用，如白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α），而这些细胞因子可能最终影响由新冠病毒引起的细胞因子风暴。本研究分析了口服和腹腔注射（IP）二甲双胍给药途径在脂多糖（LPS）诱导的细胞因子风暴小鼠模型中的抗炎作用。总共60只雌性BALB/c小鼠被随机分为六组之一：i）对照组；ii）LPS模型组；iii）口服生理盐水+LPS组；iv）口服二甲双胍+LPS组；v）腹腔注射生理盐水+LPS组；vi）腹腔注射二甲双胍+LPS组。给小鼠施用二甲双胍或生理盐水30天，之后对五个治疗组腹腔注射0.5mg/kg LPS以诱导细胞因子风暴。处死小鼠并测量血清细胞因子水平。口服或腹腔注射二甲双胍预处理均显著降低了LPS注射后白细胞介素-1（IL-1）、IL-6和TNF-α的升高。两种二甲双胍给药途径均显著降低了IL-1和TNF-α水平，尽管腹腔注射二甲双胍在降低IL-6水平方面似乎比口服二甲双胍更有效。二甲双胍的口服或腹腔注射给药途径对IL-17水平均未显示出显著影响。基于其抑制促炎性LPS诱导的细胞因子风暴的能力，二甲双胍在改善由细胞因子水平升高引起的人类疾病方面可能具有潜在的未来益处。
