Low-dose intramuscular polymyxin B improves survival of septic rats.

Polymyxin B (PLB) is a cationic antibiotic that also stoichiometrically neutralizes the lipid A moiety of endotoxin. We examined effects of a small dose of PLB on the mortality of rats with cecal ligation and puncture, on LPS-stimulated nitric oxide (NO) production, and on tumor necrosis factor a (TNF±) production by isolated rat Kupffer cells. Materials and Methods: 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 group: n = 16). Plasma endotoxin was measured at 3 and 24 h after the CLP by the Endospecy test. This was compared with survival. In vitro studies: Kupffer cells were isolated from the normal rat liver. The cells were incubated with LPS or LPS+PLB. After 24 h, NO and TNF± content were measured using the Griess and ELISA methods, respectively. Results: Low dose PLB significantly decreased the endotoxin levels at both 3 and 24 h (5.5 ±2.1 pg/mL 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 control group vs. 100% in the PLB treated group on 3 days after CLP, p < .001). PLB also attenuated NO and TNF± production from the Kupffer cells. Conclusion: Intramuscular PLB administered in low doses may improve the mortality of sepsis.