Vascular endothelial growth factor blockade reduces plasma cytokines in a murine model of polymicrobial sepsis

Anna Nolan, Michael D. Weiden, Gavin Thurston, Jeffrey (Jeff) Gold

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Numerous cytokines, including vascular endothelial growth factor (VEGF), are implicated in the pathogenesis of sepsis. While overexpression of VEGF produces pulmonary capillary leak, the role of VEGF in sepsis is less clear. We investigated VEGF in sepsis, utilizing a VEGF trap (VEGFT). Polymicrobial sepsis was induced in C57BL/6 mice by cecal ligation and puncture (CLP) and resulted in significantly increased plasma VEGF levels (234 vs. 46 pg/mL; p = 0.03). Inhibition of VEGF had no effect on mortality or lung leak but did attenuate plasma IL-6 (120 vs. 236 ng/mL; p = 0.02) and IL-10 (16 vs. 41 ng/mL; p = 0.03). These alterations in inflammatory cytokines were associated with increased levels of the dominant negative inhibitory C/EBPβ. In vitro, VEGF stimulated IL-6, IL-10 and reduced the inhibitory isoform of C/EBPβ in cultured macrophages. Together these data suggest VEGF can regulate inflammatory cytokine production in murine polymicrobial sepsis, via regulation of C/EBPβ.

Original languageEnglish (US)
Pages (from-to)271-278
Number of pages8
JournalInflammation
Volume28
Issue number5
DOIs
StatePublished - Oct 2004
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor A
Sepsis
Cytokines
Interleukin-10
Interleukin-6
Interleukin-16
Lung
Inbred C57BL Mouse
Punctures
Ligation
Protein Isoforms
Macrophages
Mortality

Keywords

  • C/EBPβ
  • IL-10
  • IL-6
  • Sepsis
  • VEGF

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology
  • Cell Biology

Cite this

Vascular endothelial growth factor blockade reduces plasma cytokines in a murine model of polymicrobial sepsis. / Nolan, Anna; Weiden, Michael D.; Thurston, Gavin; Gold, Jeffrey (Jeff).

In: Inflammation, Vol. 28, No. 5, 10.2004, p. 271-278.

Research output: Contribution to journalArticle

Nolan, Anna ; Weiden, Michael D. ; Thurston, Gavin ; Gold, Jeffrey (Jeff). / Vascular endothelial growth factor blockade reduces plasma cytokines in a murine model of polymicrobial sepsis. In: Inflammation. 2004 ; Vol. 28, No. 5. pp. 271-278.
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