Inhibitory Effects of Low-Dose Polymyxin B on Hemorrhage-Induced Endotoxin/Bacterial Translocation and Cytokine Formation in Rats

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Abstract
The current experiments were performed to determine the effects of a subtherapeutic dose of polymyxin B sulfate on gut origin endotoxemia/bacterial translocation, and tumor necrosis factor (TNF) and interleukin-1 (IL-1) release following hemorrhagic shock (30 mm Hg, 90 min) in rats. The results showed that significant portal and systemic endotoxemia took place in the control group (portal, 0.269 to 0.845 endotoxin units (EU)/mL; systemic, 0.164 to 0.655 EU/mL), but not in the treatment group (except 0.5 hour in portal blood: 0.207 +/- 0.094 EU/mL). Concomitantly, the incidence of bacterial translocation to the mesenteric lymph nodes and viscera were reduced significantly at 0.5, 2, 6, and 24 hours postresuscitation in animals receiving polymyxin B (p < 0.05 to 0.01), whereas there were no differences with respect to number of translocating bacteria between the two groups (p > 0.05). Marked elevation of plasma TNF levels and IL-1 activities of peritoneal macrophages were also found in untreated controls at 0.5 to 2 hours (p < 0.05) and 6 to 24 hours (p < 0.05 to 0.01), respectively, but prevented by administration of low-dose polymyxin B. The 48-hour survival rate was improved from 41.7% in the control group to 75.0% in the treatment ones (p > 0.05). These data suggest that pretreatment with a subtherapeutic dose of polymyxin B is effective to inhibit hemorrhage-induced endotoxin/bacterial translocation from the gut and excessive TNF and IL-1 production.