Dedeler Ertanıdır Elif, Duman Ipek, Eryavuz Duygu Onmaz, Ünlü Ali, Ertanıdır Mehmet, Duman Ateş
Department of Anesthesiology and Reanimation, Faculty of Medicine, Selcuk University, Konya 42130, Türkiye.
Department of Medical Pharmacology, Faculty of Medicine, Necmettin Erbakan University, Konya 42080, Türkiye.
Life (Basel). 2025 Jun 9;15(6):928. doi: 10.3390/life15060928.
Sepsis is a life-threatening condition driven by a dysregulated host immune response to infection, with cytokine overproduction contributing to organ dysfunction and high mortality. Levosimendan, a calcium sensitizer used in acute heart failure, has been proposed to exert anti-inflammatory effects, but information on its immunomodulatory effects in early sepsis remains scarce. This study aimed to investigate the dose- and time-dependent effects of levosimendan on cytokine profiles in a rat model of lipopolysaccharide (LPS)-induced sepsis. Thirty-two male Wistar albino rats were randomly assigned to four groups: sham, sepsis control, low-dose levosimendan (1 mg/kg), and high-dose levosimendan (2 mg/kg). Cytokine levels (TNF-α, IL-1β, IL-6, IL-8, IL-17, MCP-1) were measured at 5 and 10 h post-LPS administration. High-dose levosimendan significantly reduced TNF-α, IL-1β, IL-6, and MCP-1 levels by the 10th hour, accompanied by improved Murine Sepsis Scores. IL-17 and IL-6 showed biphasic responses, increasing initially and decreasing significantly later, particularly with high-dose treatment. IL-8 reduction was observed only in the high-dose group. These findings support levosimendan's dose and time-dependent anti-inflammatory effects and suggest it may modulate both early and late-phase cytokines in sepsis. Further studies are warranted to clarify its potential role in clinical sepsis management.
脓毒症是一种由宿主对感染的免疫反应失调所驱动的危及生命的病症，细胞因子过度产生会导致器官功能障碍和高死亡率。左西孟旦是一种用于急性心力衰竭的钙增敏剂，已被提出具有抗炎作用，但关于其在早期脓毒症中免疫调节作用的信息仍然匮乏。本研究旨在探讨左西孟旦在脂多糖（LPS）诱导的脓毒症大鼠模型中对细胞因子谱的剂量和时间依赖性影响。32只雄性Wistar白化大鼠被随机分为四组：假手术组、脓毒症对照组、低剂量左西孟旦组（1 mg/kg）和高剂量左西孟旦组（2 mg/kg）。在给予LPS后5小时和10小时测量细胞因子水平（TNF-α、IL-1β、IL-6、IL-8、IL-17、MCP-1）。到第10小时，高剂量左西孟旦显著降低了TNF-α、IL-1β、IL-6和MCP-1水平，同时小鼠脓毒症评分得到改善。IL-17和IL-6表现出双相反应，最初升高，随后显著降低，尤其是高剂量治疗时。仅在高剂量组观察到IL-8水平降低。这些发现支持左西孟旦的剂量和时间依赖性抗炎作用，并表明它可能调节脓毒症早期和晚期的细胞因子。有必要进行进一步研究以阐明其在临床脓毒症管理中的潜在作用。
