The Anti-Inflammatory Potential of Levosimendan in Sepsis: An Experimental Study Using an LPS-Induced Rat Model

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Abstract

Sepsis is a major cause of morbidity and mortality, with cytokine dysregulation. Levosimendan, a calcium sensitizer with cardioprotective and anti-inflammatory properties. This study investigates the effects of levosimendan on early inflammatory cytokine levels and clinical outcomes in an experimental sepsis model. A murine sepsis model was established using lipopolysaccharide administration. Animals were divided into Sham, Sepsis Control, Low-Dose Levosimendan, and High-Dose Levosimendan groups. Serum cytokine levels (TNF-α, IL-1β, IL-6, IL-8, IL-17, and MCP-1) were measured at the 5th and 10th hours. Sepsis severity was assessed using Murine Sepsis Scores (MSS). TNF-α, IL-1β, IL-6, and MCP-1 levels were significantly elevated in the sepsis control group. Both low- and high-dose levosimendan groups exhibited an initial rise in IL-17 and IL-6, followed by a significant reduction at the 10th hour. High-dose levosimendan demonstrated the most pronounced anti-inflammatory effect, with significant reductions in TNF-α, IL-1β, and MCP-1 levels. MSS scores were significantly lower in levosimendan-treated groups, with high-dose treatment showing the greatest improvement. Levosimendan exerts a dose-dependent immunomodulatory effect in experimental sepsis, with high doses effectively suppressing pro-inflammatory cytokine levels and improving clinical outcomes. These findings highlight the potential therapeutic role of levosimendan in sepsis management, warranting further investigation in clinical settings.

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