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Early enhanced local neutrophil recruitment in peritonitis-induced sepsis improves bacterial clearance and survival.

Abstract
Neutrophils are critical for the rapid eradication of bacterial pathogens, but they also contribute to the development of multiple organ failure in sepsis. We hypothesized that increasing early recruitment of neutrophils to the focus of infection will increase bacterial clearance and improve survival. Sepsis was induced in mice, using cecal ligation and puncture (CLP); blood samples were collected at 6 and 24 h; and survival was followed for 28 d. In separate experiments, peritoneal bacteria and inflammatory cells were measured. Septic mice predicted to die based on IL-6 levels (Die-P) had higher concentrations of CXCL1 and CXCL2 in the peritoneum and plasma compared with those predicted to live (Live-P). At 6 h, Live-P and Die-P had equivalent numbers of peritoneal neutrophils and bacteria. In Die-P mice the number of peritoneal bacteria increased between 6 and 24 h post-CLP, whereas in Live-P it decreased. The i.p. injection of CXCL1 and CXCL2 in naive mice resulted in local neutrophil recruitment. When given immediately after CLP, CXC chemokines increased peritoneal neutrophil recruitment at 6 h after CLP. This early increase in neutrophils induced by exogenous chemokines resulted in significantly fewer peritoneal bacteria by 24 h [CFU (log) = 6.04 versus 4.99 for vehicle versus chemokine treatment; p < 0.05]. Chemokine treatment significantly improved survival at both 5 d (40 versus 72%) and 28 d (27 versus 52%; p < 0.02 vehicle versus chemokines). These data demonstrate that early, local treatment with CXC chemokines enhances neutrophil recruitment and clearance of bacteria as well as improves survival in the CLP model of sepsis.
AuthorsFlorin L Craciun, Elizabeth R Schuller, Daniel G Remick
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 185 Issue 11 Pg. 6930-8 (Dec 01 2010) ISSN: 1550-6606 [Electronic] United States
PMID21041722 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Cytokines
  • Inflammation Mediators
Topics
  • Animals
  • Bacteria (growth & development, immunology, pathogenicity)
  • Cecum
  • Cytokines (biosynthesis, metabolism)
  • Disease Models, Animal
  • Female
  • Inflammation Mediators (administration & dosage, metabolism)
  • Ligation
  • Mice
  • Mice, Inbred ICR
  • Neutrophil Infiltration (immunology)
  • Neutrophils (immunology, microbiology, pathology)
  • Peritonitis (immunology, microbiology, mortality)
  • Predictive Value of Tests
  • Punctures
  • Sepsis (immunology, microbiology, mortality)
  • Survival Analysis

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