Early effects of lipopolysaccharide on cytokine release, hemodynamic and renal function in newborn piglets

Eunice John*, Priya Pais, Nicholas Furtado, Anthony Chin, Jayant Radhakrishnan, Linda Fornell, Adisorn Lumpaopong, Ulf H. Beier

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Gram-negative sepsis in newborns is associated with high mortality and morbidity. Lipopolysaccharide (LPS) and cytokines released upon exposure to gram-negative sepsis are well known to be involved in the pathophysiology. Objective: In this report we investigate cytokine release, hemodynamic, and renal function induced by LPS in a newborn animal model with the intention to further examine early changes in gram-negative sepsis. Methods: Five 7- to 10-day-old domestic piglets were anesthetized and catheters placed in the jugular veins, left ventricle, and femoral artery. Urine output was monitored via suprapubic cystostomy. Mean arterial pressure, heart rate, and arterial blood gases were continuously monitored. Thirty minutes after line placement and obtaining baseline values, 0.06 μg/kg LPS were administered intravenously. One, 2, and 3 h later samples were taken to monitor tumor necrosis factor (TNF)-α, interleukin (IL)-1β, endothelin, and nitric oxide (NO)/nitrate via ELISA. In addition, blood flow was assessed by the microsphere method. Results: Our data show an initial surge of TNF-α and IL-1β at 1 h after exposure to LPS. NO/nitrate, endothelin, and hemodynamic as well as metabolic changes became apparent mostly 3 h after exposure, by which time TNF-α and IL-1β fell back to baseline. Conclusions: Our sepsis model suggests a brief initial TNF-α and IL-1β surge following LPS challenge; however, their effects become apparent by the time the levels are already subsiding. The emergence of vasoactive substances, NO and endothelin, precedes the first substantial clinical symptoms.

Original languageEnglish (US)
Pages (from-to)106-112
Number of pages7
JournalNeonatology
Volume93
Issue number2
DOIs
StatePublished - Feb 1 2008

Keywords

  • Early cytokine response
  • Endotoxin
  • Gram-negative sepsis
  • Renal function

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental Biology

Fingerprint Dive into the research topics of 'Early effects of lipopolysaccharide on cytokine release, hemodynamic and renal function in newborn piglets'. Together they form a unique fingerprint.

Cite this