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

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.

In vivo porcine lipopolysaccharide inflammation models to study immunomodulation of drugs

“…LPS infusion started at a rate of 0.625 g/kg/h. On the other hand, John et al (2008) observed a 9-fold increase in TNF-␣ levels p.a. of an i.v.…”

“…In this respect, it has been suggested that IL-1␤ production is less sensitive to the effects of endotoxin compared to TNF-␣ and IL-6 (Myers et al, 2003). Nevertheless, John et al (2008) determined a 5-fold increase in the concentration of IL-1␤ at 1 h p.a. of an LPS dose as low as 0.06 g/kg BW.…”

“…infusion. While a single LPS bolus administration better reflects the sequence of events following LPS challenge, a continuous LPS infusion would imitate more accurately a clinical endotoxemia/septicemia, since endotoxin remains in circulation for a longer period (Fink and Heard, 1990;Olson et al, 1995;John et al, 2008). As described, endotoxin is continuously produced and released by surviving bacteria in Gram-negative bacterial sepsis (Schrauwen et al, 1988).…”

Protective Effect of Naringenin Against Lipopolysaccharide-Induced Injury in Normal Human Bronchial Epithelium via Suppression of MAPK Signaling

“…Lipopolysaccharide (LPS) is a potent inflammatory stimulant which induced airway inflammation in normal subjects and to enhance airway reactivity in asthmatics [4,5]. LPS induces HBEC from asthmatics secreting higher amounts of pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), and chemokines, such as interleukin-6 (IL-6), to promoting the recruitment of various leukocytes, primarily neutrophils, to the site of infection [6,7].…”

Indomethacin abolishes core temperature, but not cardiovascular or renal, responses to lipopolysaccharide in conscious lambs

“…Similar responses were observed by the same group in a different study in piglets administered LPS. 12 However, to date there have been no studies performed in young animals in the absence of the confounding effects of surgery and anaesthesia on the measured variables evaluating cardiovascular or renal responses to LPS or the role for prostaglandins in mediating these responses. Therefore, in the present experiments, we investigated the effects of LPS on systemic and renal haemodynamics, as well as on several parameters of renal function and core temperature (Tc), in conscious, chronically instrumented lambs.…”