Repetitive Pneumoperitoneum with Ozonized Oxygen as a Preventive in Lethal Polymicrobial Sepsis in Rats

AbstractFluid resuscitation following severe inflammation-induced hypoperfusion is critical for the restoration of hemodynamics and the prevention of multiorgan dysfunction syndrome during septic shock. Fluid resuscitation with commercially available crystalloid and colloid solutions only provides transient benefits, followed by fluid extravasation and tissue edema through the inflamed endothelium. The increased molecular weight (M.W.) of polymerized human serum albumin (PolyHSA) can limit fluid extravasation, leading to restoration of hemodynamics. In this prospective study, we evaluated how fluid resuscitation with PolyHSA impacts the hemodynamic and immune response in a lipopolysaccharide (LPS) induced endotoxemia mouse model. Additionally, we evaluated fluid resuscitation with PolyHSA in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Resuscitation with PolyHSA attenuated the immune response and improved the maintenance of systemic hemodynamics and restoration of microcirculatory hemodynamics. This decrease in inflammatory immune response and maintenance of vascular wall shear stress likely contributes to the maintenance of vascular integrity following fluid resuscitation with PolyHSA. The sustained restoration of perfusion, decrease in pro-inflammatory immune response, and improved vascular integrity that results from the high M.W. of PolyHSA indicates that a PolyHSA based solution is a potential resuscitation fluid for endotoxic and septic shock.

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Bone Marrow Mesenchymal Stromal Cells on Silk Fibroin Scaffolds to Attenuate Polymicrobial Sepsis Induced by Cecal Ligation and Puncture

Polymers ◽

10.3390/polym13091433 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1433

Author(s):

Ok-Hyeon Kim ◽

Jun-Hyung Park ◽

Jong-In Son ◽

Ok-Ja Yoon ◽

Hyun-Jung Lee

Keyword(s):

Bone Marrow ◽

Cecal Ligation ◽

Biological Properties ◽

Pge2 Production ◽

Polymicrobial Sepsis ◽

Control Surface ◽

Related Factors ◽

Cox 2 ◽

Anti Inflammatory

Suitable scaffolds with appropriate mechanical and biological properties can improve mesenchymal stromal cell (MSC) therapy. Because silk fibroins (SFs) are biocompatible materials, they were electrospun and applied as scaffolds for MSC therapy. Consequently, interferon (IFN)-primed human bone marrow MSCs on SF nanofibers were administered into a polymicrobial sepsis murine model. The IL-6 level gradually decreased from 40 ng/mL at 6 h after sepsis to 35 ng/mL at 24 h after sepsis. The IL-6 level was significantly low as 5 ng/mL in primed MSCs on SF nanofibers, and 15 ng/mL in primed MSCs on the control surface. In contrast to the acute response, inflammation-related factors, including HO-1 and COX-2 in chronic liver tissue, were effectively inhibited by MSCs on both SF nanofibers and the control surface at the 5-day mark after sepsis. An in vitro study indicated that the anti-inflammatory function of MSCs on SF nanofibers was mediated through enhanced COX-2-PGE2 production, as indomethacin completely abrogated PGE2 production and decreased the survival rate of septic mice. Thus, SF nanofiber scaffolds potentiated the anti-inflammatory and immunomodulatory functions of MSCs, and were beneficial as a culture platform for the cell therapy of inflammatory disorders.

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GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation

Antioxidants ◽

10.3390/antiox10081175 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1175

Author(s):

Johanna Helmstädter ◽

Karin Keppeler ◽

Franziska Aust ◽

Leonie Küster ◽

Katie Frenis ◽

...

Keyword(s):

Oxidative Stress ◽

Vascular Function ◽

Vascular Inflammation ◽

Cecal Ligation ◽

Isometric Tension ◽

Polymicrobial Sepsis ◽

Dot Blot ◽

Markers Of Inflammation ◽

Anti Inflammatory ◽

And Oxidative Stress

Sepsis causes high mortality in the setting of septic shock. LEADER and other trials revealed cardioprotective and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) analogs like liraglutide (Lira). We previously demonstrated improved survival in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of GLP-1 degradation. Here we investigate the effects of Lira in the polymicrobial sepsis model of cecal ligation and puncture (CLP). C57BL/6J mice were intraperitoneally injected with Lira (200 µg/kg/d; 3 days) and sepsis induced by CLP after one day of GLP-1 analog treatment. Survival and body temperature were monitored. Aortic vascular function (isometric tension recording), protein expression (immunohistochemistry and dot blot) and gene expression (qRT-PCR) were determined. Endothelium-dependent relaxation in the aorta was impaired by CLP and correlated with markers of inflammation (e.g., interleukin 6 and inducible nitric oxide synthase) and oxidative stress (e.g., 3-nitrotyrosine) was higher in septic mice, all of which was almost completely normalized by Lira therapy. We demonstrate that the GLP-1 analog Lira ameliorates sepsis-induced endothelial dysfunction by the reduction of vascular inflammation and oxidative stress. Accordingly, the findings suggest that the antioxidant and anti-inflammatory effects of GLP-1 analogs may be a valuable tool to protect the cardiovascular system from dysbalanced inflammation in polymicrobial sepsis.

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Microparticle Activity Is Increased In Murine Polymicrobial Sepsis

10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a1375 ◽

2010 ◽

Author(s):

Bushra Naveed ◽

Michael D. Weiden ◽

Ashley L. Comfort ◽

Yingdi Chen ◽

Sophia Kwon ◽

...

Keyword(s):

Polymicrobial Sepsis

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Blood-Brain Barrier Deterioration and Hippocampal Gene Expression in Polymicrobial Sepsis: An Evaluation of Endothelial MyD88 and the Vagus Nerve

PLoS ONE ◽

10.1371/journal.pone.0144215 ◽

2016 ◽

Vol 11 (1) ◽

pp. e0144215 ◽

Cited By ~ 9

Author(s):

Gerard Honig ◽

Simone Mader ◽

Huiyi Chen ◽

Amit Porat ◽

Mahendar Ochani ◽

...

Keyword(s):

Gene Expression ◽

Vagus Nerve ◽

Blood Brain Barrier ◽

Polymicrobial Sepsis ◽

Brain Barrier ◽

Blood Brain

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Polymicrobial Sepsis Alters Antigen-Dependent and -Independent Memory CD8 T Cell Functions

The Journal of Immunology ◽

10.4049/jimmunol.1303460 ◽

2014 ◽

Vol 192 (8) ◽

pp. 3618-3625 ◽

Cited By ~ 29

Author(s):

Sean Duong ◽

Stephanie A. Condotta ◽

Deepa Rai ◽

Matthew D. Martin ◽

Thomas S. Griffith ◽

...

Keyword(s):

T Cell ◽

Cd8 T Cell ◽

Polymicrobial Sepsis ◽

Cell Functions ◽

Memory Cd8 T Cell

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Modulation of tissue Toll-like receptor 2 and 4 during the early phases of polymicrobial sepsis correlates with mortality*

Critical Care Medicine ◽

10.1097/01.ccm.0000069343.27691.f3 ◽

2003 ◽

Vol 31 (6) ◽

pp. 1808-1818 ◽

Cited By ~ 113

Author(s):

David L. Williams ◽

Tuanzhu Ha ◽

Chuanfu Li ◽

John H. Kalbfleisch ◽

John Schweitzer ◽

...

Keyword(s):

Polymicrobial Sepsis ◽

Toll Like Receptor ◽

Toll Like Receptor 2 ◽

Early Phases

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Critical Role for CXC Ligand 10/CXC Receptor 3 Signaling in the Murine Neonatal Response to Sepsis

Infection and Immunity ◽

10.1128/iai.01291-10 ◽

2011 ◽

Vol 79 (7) ◽

pp. 2746-2754 ◽

Cited By ~ 27

Author(s):

Alex G. Cuenca ◽

James L. Wynn ◽

Kindra M. Kelly-Scumpia ◽

Philip O. Scumpia ◽

Lizette Vila ◽

...

Keyword(s):

Neonatal Sepsis ◽

Bacterial Infections ◽

Critical Role ◽

Peritoneal Macrophages ◽

Polymicrobial Sepsis ◽

Adjuvant Effect ◽

Toll Like Receptor 4 ◽

Cxcr3 Expression ◽

Neonatal Response ◽

Granulocyte Function

ABSTRACTPrevious studies have suggested that neonates rely heavily on innate immunity for their antimicrobial response to bacterial infections. However, the innate immune response by neonates to bacterial infection remains poorly characterized. Here, we show that in a murine model of neonatal polymicrobial sepsis, CXC ligand 10 (CXCL10) concentrations increase in the blood and peritoneum concordant with the peritoneal recruitment of granulocytes and macrophages. Additionally, CXC receptor 3 (CXCR3) expression on elicited peritoneal macrophages and granulocytes increases following sepsis. Blockade of CXCL10 worsens not only recruitment and phagocytic function of peritoneal granulocytes and macrophages but also survival. Deletion of CXCR3 also significantly increases mortality to a septic challenge. Finally, we demonstrate that the protective adjuvant effect of pretreatment with a Toll-like receptor 4 agonist to neonatal sepsis is dependent on an endogenous CXCL10 response and that pretreatment of neonates with CXCL10 can also significantly improve macrophage and granulocyte function and modestly improve outcome to polymicrobial sepsis. Together, these data suggest a critical role for CXCL10 signaling during neonatal sepsis.

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