Low-dose intramuscular polymyxin B improves survival of septic rats

Polymyxin B (PLB) is a cationic antibiotic that also stoichiometrically neu tralizes the lipid A moiety of endotoxin. We examined effects of a small do se of PLB on the mortality of rats with cecal ligation and puncture, on LPS -stimulated nitric oxide (NO) production, and on tumor necrosis factor alph a (TNF alpha) production by isolated rat Kupffer cells. Materials and Metho ds: In vivo studies: Cecal ligation and puncture (CLP) was performed under anesthesia in 28 rats. One hour after CLP, either 600 U/kg of PLB or saline was administered intramuscularly every 6 h (PLB group: n = 12; control gro up: n = 16). Plasma endotoxin was measured at 3 and 24 h after the CLP by t he Endospecy test. This was compared with survival. In vitro studies: Kupff er cells were isolated from the normal rat liver. The cells were incubated with LPS or LPS+PLB. After 24 h, NO and TNF alpha content were measured usi ng the Griess and ELISA methods, respectively. Results: Low dose PLB signif icantly decreased the endotoxin levels at both 3 and 24 h (5.5 +/- 2.1 pg/m L vs. 32.8 +/- 3.6 at 3 h; 26.1 +/- 6.1 vs. 49.1 +/- 5.6 at 24 h (p < .05) after CLP. PLB significantly improved survival of CLP rats (68.8% in the co ntrol group vs. 100% in the PLB treated group on 3 days after CLP, p < .001 ). PLB also attenuated NO and TNF alpha production from the Kupffer cells. Conclusion: Intramuscular PLB administered in low doses may improve the mor tality of sepsis.