Effect of polymyxin B on experimental shock from meningococcal and Escherichia coli endotoxins.
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 meningococcal lipooligosaccharide (LOS) and compared with an LD80 of Escherichia coli O111: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 less than .05) and improved 24-h survival (P less than .05). In contrast, PMB given before E. coli LPS challenge increased serum bicarbonate levels, decreased TNF levels, and improved 24-h survival (all, P less than .05). In vitro studies confirmed that PMB at 10 micrograms/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.
Baldwin
G
G
Department of Medicine, Children's Hospital, Boston, MA 02115.
Alpert
G
G
Caputo
G L
GL
Baskin
M
M
Parsonnet
J
J
Gillis
Z A
ZA
Thompson
C
C
Siber
G R
GR
Fleisher
G R
GR
D000818:Animals; D001639:Bicarbonates / Q000097:blood; D001794:Blood Pressure; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli; D006339:Heart Rate; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D009345:Neisseria meningitidis; D011112:Polymyxin B / Q000627:therapeutic use*; D011817:Rabbits; D012772:Shock, Septic / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000503:physiopathology
D001639:Bicarbonates; D004731:Endotoxins; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides; C044101:endotoxin, Escherichia coli; D011112:Polymyxin B