Experimental TLR4 inhibition improves intestinal microcirculation in endotoxemic rats

Juan Zhou, Marieke Soltow, Katrin Zimmermann, Dragan Pavlovic, Brent Johnston, Christian Lehmann

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

7 Citas (Scopus)

Resumen

Introduction: Toll like receptor 4 (TLR4) represents a critical cellular link for endotoxin-induced pathology. The aim of this study was to evaluate the potential role of TLR4 inhibition on the intestinal microcirculation during experimental endotoxemia. Materials and methods: The intestinal microcirculation was studied by intravital microscopy in four groups of Lewis rats (n = 10 per group): healthy controls (CON group), endotoxemic animals (15. mg/kg lipopolysaccharide, LPS group), endotoxemic animals treated with a TLR4 antagonist (1. mg/kg CRX-526, LPS. +. CRX526 group), and controls treated with CRX-526 (C-CRX526 group). Plasma samples were obtained for cytokine measurements at the end of the experiments. Results: Endotoxemia significantly increased leukocyte adhesion in intestinal submucosal venules (e.g., V1 venules: CON 20.4±6.5n/mm2, LPS 237.5±36.2n/mm2, p<0.05) and reduced capillary perfusion of the intestinal wall (e.g., longitudinal muscular layer: CON 112.5±5.9cm/cm2, LPS 71.3±11.0cm/cm2, p<0.05) at 2h. TLR4 inhibition significantly reduced endotoxemia-associated leukocyte adhesion (V1 venules: 104.3±7.8n/mm2) and improved capillary perfusion (longitudinal muscular layer: 111.0±12.3cm/cm2). Cytokine release was not significantly affected. Conclusions: The TLR4 pathway may be a target in clinical Gram-negative sepsis since administration of the TLR4 antagonist CRX-526 improved intestinal microcirculation parameters in experimental endotoxemia.

Idioma originalEnglish
Páginas (desde-hasta)33-37
Número de páginas5
PublicaciónMicrovascular Research
Volumen101
DOI
EstadoPublished - sep. 1 2015

Nota bibliográfica

Publisher Copyright:
© 2015 Elsevier Inc..

ASJC Scopus Subject Areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

PubMed: MeSH publication types

  • Journal Article

Huella

Profundice en los temas de investigación de 'Experimental TLR4 inhibition improves intestinal microcirculation in endotoxemic rats'. En conjunto forman una huella única.

Citar esto