Endotoxin, interleukin-6 and tumor necrosis factor concentrations in equine acute abdominal disease: relation to clinical outcome

Abstract

Serial peri-operative plasma and serum samples from 55 horses suffering from acute abdominal disease and presented for surgical intervention were assayed for the presence of endotoxins (lipopolysaccharides; LPS), tumor necrosis factor (TNF) and interleukin-6 (IL-6). At study entry, venous blood was collected for blood cultures. Intra-operatively collected ascitic fluid samples were assayed for the presence of LPS. The clinical course of the disease was documented. Four horses were excluded from the study. At study entry, 21 of the 51 horses (41%) had increased platelet-rich plasma LPS concentrations, i.e. &ge; 5 ng/l (mean 35.5; range 7-197 ng/l), in 34 horses (67%) IL-6 concentrations were increased, i.e. exceeding 35 ng/l (mean 364; range 36&mdash;1762 ng/l). Detectable TNF was present in 5 horses (10%); 3 of them died spontaneously during surgery. In all TNF positive samples, markedly increased LPS and IL-6 concentrations were detected. Study entry IL-6 concentrations were significantly higher in non-surviving (mean 394; range < 20&mdash;1762 ng/l) than in surviving horses (mean 116; range < 20&mdash;894 ng/l; P < 0.0002). This was most evident when non-surviving horses with inflamed bowel disease were considered (mean 1096; range 650&mdash;1762 ng/l; P < 0.0001). Positive ascitic fluid LPS concentrations (&ge; 3 ng/l) were encountered in 18 horses. There was no significant correlation between the LPS concentrations in ascites and plasma. Study entry concentrations of IL-6 were significantly correlated with LPS concentrations (r = 0.62; P < 0.001) and were inversely correlated with platelet counts (r = -0.46; P < 0.002). The magnitude of a calculated LPS-cytokine score strongly correlated with mortality (P < 0.001). Receiver operating characteristic (ROC) curve analysis showed that the IL-6 assay had reasonable accuracy for the prediction of unfavorable outcome (i.e. the area under the curve equalled 0.72), in contrast to the LPS assay. The results indicate that LPS, TNF and IL-6 are predominantly released in the systemic circulation of horses suffering from inflamed and ischemic bowel disease. IL-6 concentrations have predictive value for unfavorable outcome and the simultaneous presence of increased LPS, TNF and IL-6 concentrations is especially associated with a poor clinical condition and outcome.The clinical signs culminating in equine acute abdominal disease range widely, from mild symptoms to fulminant shock with profound metabolic and respiratory acidosis, hypotension, and hypovolemia with death ocat RYERSON UNIV on June 18, 2015 ini.sagepub.com Downloaded from

Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro

“…The expression of IL-6 is associated with the concentration of TNF-α and correlated with the clinical outcome (Calandra et al 1991;Yoshimoto et al 1992). In horses, IL-6 concentrations have predictive value for unfavorable outcome and the simultaneous presence of increased LPS and TNF-α (Steverink et al 1995). Increased concentrations of IL-6 have been associated with a poor clinical condition and outcome in horses (Steverink et al 1995).…”

“…In horses, IL-6 concentrations have predictive value for unfavorable outcome and the simultaneous presence of increased LPS and TNF-α (Steverink et al 1995). Increased concentrations of IL-6 have been associated with a poor clinical condition and outcome in horses (Steverink et al 1995).…”

“…Although endotoxin stimulates an array of cytokine and inflammatory mediators, only a few key cytokines have been described in equine endotoxemia. Tumor necrosis factor-α (TNF-α), IL-1 and IL-6 are key pro-inflammatory cytokines released during endotoxemia in horses Steverink et al 1995;Veenman et al 2002). These cytokines are important in the onset and development of septic shock and a direct relationship between blood concentrations of TNF-α, IL-6 and mortality has been established in horses, humans and rodents (Steverink et al 1995;Veenman et al 2002).…”

“…In equine neonates, endotoxemia commonly results from gram negative septicemia (Lavoie et al 1990). Approximately 30-40% of horses presented to referral hospitals with clinical signs of colic and 40-50% of neonatal foals presented with septicemia have endotoxin in their systemic circulation (Barton et al 1998b;Steverink et al 1995). Endotoxemia in horses with gastrointestinal diseases is strongly correlated with outcome (Thoefner et al 2001;Tinker et al 1997) and represents a common sequel that increases morbidity and mortality (Hunt et al 1986).…”

“…High TNF-α and/or IL-6 concentrations have been associated with an unfavorable outcome (Barton and Collatos 1999;MacKay et al 1991;Steverink et al 1995). IL-10 blocks the in vitro and in vivo production of TNF-α and decreases LPS toxicity as well as LPS-induced mortality in humans and mice .…”