Effect of Polymyxin B on Experimental Shock from Meningococcal and Escherichia coli Endotoxins

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Abstract
Meningococcemia is the most frequent cause of septic shock in healthy children. To determine whether polymyxin B (PMB) might improve mortality from meningococcal shock, its protective activity was evaluated in rabbits challenged with an LD90 of meningococcallipooligosaccharide (LOS) and compared with an LD80 of Escherichia coli 0111:B4 lipopolysaccharide (LPS). PMB (5 mg/kg) administered intravenously 30 min before meningococcal LOS challenge had no significant effect on heart rate, mean arterial pressure, serum bicarbonate, serum tumor necrosis factor (TNF) levels, or survival relative to controls. However, PMB premixed with LOS in vitro increased serum bicarbonate levels (P < .05) and improved 24-h survival (P < .05). In contrast, PMB given before E. coli LPS challenge increased serum bicarbonate levels, decreased TNF levels,and improved 24-h survival (all, P E. coli .05). In vitro studies confirmed that PMB at 10 µg/ml neutralized E. coli LPS but not meningococcal LOS activity. Thus, pretreatment with PMB apparently protects rabbits against shock induced by E. coli LPS but not by meningococcal LOS.

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