Selective decontamination of the digestive tract in severe CHF eradicated intestinal AGNB (P<0.00001), decreased monocyte CD14 expression (P=0.03), and improved flow-mediated dilation (P=0.002).
Does selective decontamination of the digestive tract (SDD) reduce monocyte activation and improve endothelial function in patients with severe chronic heart failure?
Selective intestinal decontamination reduces monocyte activation and improves peripheral endothelial function in patients with severe chronic heart failure, suggesting a potential anti-inflammatory benefit.
BACKGROUND AND AIMS: Endotoxin, derived from intestinal aerobic Gram-negative bacilli (AGNB), could be an important monocyte activator in chronic heart failure (CHF). The effect of selective decontamination of the digestive tract (SDD) on intracellular monocyte cytokine production, monocyte CD14 expression, circulating endotoxin and cytokines, and flow-mediated dilation (FMD) was studied in patients with severe CHF. METHODS AND RESULTS: Ten patients with CHF (NYHA class III-IV) were enrolled in a non-placebo controlled pilot trial involving the administration of SDD (polymyxin B, tobramycin) for 8 weeks. One patient was later excluded due to cardiac transplantation. Before treatment, after 4 and 8 weeks therapy, and 6 weeks post-treatment, monocyte CD14 expression, intracellular monocyte production of interleukin-1beta IL-1beta, interleukin-6 IL-6, tumour necrosis factor (TNF)-alpha with and without lipopolysaccharide (LPS) stimulation were measured. Concentrations of endotoxin and cytokines (IL-1beta, IL-6, TNF-alpha) were also determined. AGNB in faeces, intestinal endotoxin and FMD were assessed at baseline, after 4 weeks of treatment and 6 weeks post-treatment. SDD eradicated intestinal AGNB (P<0.00001) and decreased faecal endotoxin concentrations (P<0.00001). There was a significant decline in monocyte CD14 expression (P=0.03) and in IL-1beta (P=0.0001), IL-6 (P=0.02) and TNF-alpha (P=0.0002) production after 4 and 8 weeks of treatment in the basal state and for IL-1beta (P=0.008) and IL-6 (P=0.005) after LPS stimulation. FMD significantly improved at 4 weeks and returned to baseline after treatment discontinuation (P=0.002). Circulating concentrations of endotoxin and cytokines remained unchanged. CONCLUSION: Reduction of the intestinal endotoxin pool led to a decrease in monocyte CD14 expression and intracellular cytokine production in patients with severe CHF. The improvement of peripheral endothelial function could be a marker of the anti-inflammatory effect of SDD.
Conraads et al. (2004) studied Advanced Chronic Heart Failure (n=10). Selective decontamination of the digestive tract (polymyxin B, tobramycin) vs. Baseline (no placebo control) was evaluated on Intracellular monocyte cytokine production, monocyte CD14 expression, circulating endotoxin and cytokines, and flow-mediated dilation. Selective decontamination of the digestive tract in severe CHF eradicated intestinal AGNB (P<0.00001), decreased monocyte CD14 expression (P=0.03), and improved flow-mediated dilation (P=0.002).
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