Early Effects of Lipopolysaccharide on Cytokine Release, Hemodynamic and Renal Function in Newborn Piglets

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 mug/kg LPS were administered intravenously. One, 2, and 3 h later samples were taken to monitor tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, 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-alpha and IL-1beta 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-alpha and IL-1beta fell back to baseline.

Conclusions: Our sepsis model suggests a brief initial TNF-alpha and IL-1beta 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.