Investigation of the potential immunomodulatory effects of resveratrol on equine whole blood: An in vitro investigation.

Horses affected with gastrointestinal conditions such as colic or colitis are at substantial risk for translocation of bacterial components such as lipopolysaccharide (LPS, endotoxin) from the gastrointestinal tract into circulation resulting in systemic inflammation and subsequent morbidity and mortality. Therefore, there is a need for effective preventive and treatment strategies aimed at minimizing the host's inflammatory reaction to these pathogen-associated molecular patterns (PAMPs) from gastrointestinal disease. Resveratrol (RES, trans-3,5,4'-trihydroxystilbene) is a phytoalexin commonly found in fruits and beverages, including red wine. Health benefits associated with the consumption of red wine have been attributed to RES. Resveratrol has been significantly shown to exert a powerful anti-inflammatory effect in laboratory animals subjected to experimental endotoxemia/sepsis. Therefore, the objective of this study was to determine in vitro whether RES had an inhibitory effect on the production of tumor necrosis factor (TNF) in cultivated whole blood (Cwb) following stimulation by PAMPs. We hypothesized that RES would inhibit TNF production in Cwb following stimulation by LPS or lipoteichoic acid (LTA). Production of TNF bioactivity in Cwb was measured in the presence of phosphate buffered saline (control), ethanol (solvent control), dexamethasone (anti-inflammatory control), LPS, LTA, and three different concentrations of RES. Both LPS and LTA stimulated TNF production, and addition of dexamethasone was inhibitory to this effect. An anti-inflammatory effect for RES was not demonstrated under the current experimental conditions. Further studies are required to characterize the effect of RES on the equine innate immune system during systemic inflammation.

Evaluation of the anti-endotoxin effects of polymyxin B in a feline model of endotoxemia.

Directed, effective therapies for feline sepsis are needed to reduce the high morbidity and mortality associated with this disease. We investigated the anti-endotoxin effects of polymyxin B (PMB) in a blinded, placebo controlled fashion, both ex vivo in a feline whole blood culture system and in vivo, using a low-dose endotoxin infusion in cats. Serial measures of systemic inflammation, and hemodynamic stability, were compared between groups. Ex vivo, PMB significantly decreased lipopolysaccharide-induced tumor necrosis factor (TNF) production from whole blood. PMB (1mg/kg over 30min) demonstrated anti-endotoxin effects in vivo, including decreased peak plasma TNF activity (P<0.001) and increased white blood cell count (P=0.019), with no adverse effects. Given the apparent safety and anti-endotoxin effects of PMB in this endotoxemia model, a carefully designed, randomized, blinded, placebo controlled clinical trial evaluating the use of PMB in naturally occurring Gram-negative feline sepsis should be considered.