INHIBITORY EFFECTS OF LOW-DOSE POLYMYXIN-B ON HEMORRHAGE-INDUCED ENDOTOXIN BACTERIAL TRANSLOCATION AND CYTOKINE FORMATION IN RATS/

The current experiments were performed to determine the effects of a s ubtherapeutic dose of polymyxin B sulfate on gut origin endotoxemia/ba cterial translocation, and tumor necrosis factor (TNF) and interleukin -1 (IL-1) release following hemorrhagic shock (30 mm Hg, 90 min) in ra ts. The results showed that significant portal and systemic endotoxemi a rook place in the control group (portal, 0.269 to 0.845 endotoxin un its (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). Conco mitantly, the incidence of bacterial translocation to the mesenteric l ymph 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 tr anslocating bacteria between the two groups (p > 0.05). Marked elevati on of plasma TNF levels and IL-1 activities of peritoneal macrophages mere also found in untreated controls at 0.5 ro 2 hours (p < 0.05) and 6 to 24 hours (p < 0.05 to 0.01), respectively, but prevented by admi nistration of low-dose polymyxin B. The 48-hour survival rate was impr oved 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 d ose of polymyxin B is effective to inhibit hemorrhage-induced endotoxi n/bacterial translocation from the gut and excessive TNF and IL-1 prod uction.