Abstract

BackgroundAn imbalance between overwhelming inflammation and lymphocyte apoptosis is the main cause of high mortality in patients with sepsis. Baicalin, the main active ingredient of the Scutellaria root, exerts anti-inflammatory, anti-apoptotic, and even antibacterial properties in inflammatory and infectious diseases. However, the therapeutic effect of baicalin on polymicrobial sepsis remains unknown.Methodology/Principal FindingsPolymicrobial sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice. Mice were infused with baicalin intraperitoneally at 1 h, 6 h and 12 h after CLP. Survival rates were assessed over the subsequent 8 days. Bacterial burdens in blood and peritoneal cavity were calculated to assess the bacterial clearance. Neutrophil count in peritoneal lavage fluid was also calculated. Injuries to the lung and liver were detected by hematoxylin and eosin staining. Levels of cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10 and IL-17, in blood and peritoneum were measured by enzyme-linked immunosorbent assay. Adaptive immune function was assessed by apoptosis of lymphocytes in the thymus and counts of different cell types in the spleen. Baicalin significantly enhanced bacterial clearance and improved survival of septic mice. The number of neutrophils in peritoneal lavage fluid was reduced by baicalin. Less neutrophil infiltration of the lung and liver in baicalin-treated mice was associated with attenuated injuries to these organs. Baicalin significantly reduced the levels of proinflammatory cytokines but increased the level of anti-inflammatory cytokine in blood and peritoneum. Apoptosis of CD3+ T cell was inhibited in the thymus. The numbers of CD4+, CD8+ T lymphocytes and dendritic cells (DCs) were higher, while the number of CD4+CD25+ regulatory T cells was lower in the baicalin group compared with the CLP group.Conclusions/SignificanceBaicalin improves survival of mice with polymicrobial sepsis, and this may be attributed to its antibacterial property as well as its anti-inflammatory and anti-apoptotic effects.

Highlights

  • Sepsis and sequential multiple organ failure/dysfunction syndrome (MOF/MODS) remain to be the leading cause of death in intensive care units, despite the progression of medical care [1,2]

  • In order to investigate whether baicalin was benefit to cecal ligation and puncture (CLP) mice, survival was first assessed at day 8 after CLP

  • This study for the first time examined the effects of baicalin on polymicrobial sepsis induced by CLP

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Summary

Introduction

Sepsis and sequential multiple organ failure/dysfunction syndrome (MOF/MODS) remain to be the leading cause of death in intensive care units, despite the progression of medical care [1,2]. In the early phase of sepsis, overwhelming inflammatory response is initiated after microbial infection [3]. During this stage, cytokine storm is triggered, as well as excessive neutrophils recruitment in multiple organs, complement system activation and coagulation dysfunction. Cytokine storm is triggered, as well as excessive neutrophils recruitment in multiple organs, complement system activation and coagulation dysfunction This proinflammatory state has been defined as being a systemic inflammatory response syndrome (SIRS) [4]. The therapeutic effect of baicalin on polymicrobial sepsis remains unknown

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