Limulus antilipopolysaccharide factor protects rabbits from meningococcal endotoxin shock.
Limulus antilipopolysaccharide factor (LALF), an 11.8-kDa peptide isolated from amebocytes of Limulus polyphemus, neutralizes meningococcal lipooligosaccharide (LOS)-induced gelation of limulus amebocyte lysate. Rabbits challenged with an LD90 of LOS (10 micrograms/kg) premixed with LALF in vitro (n = 10) had significantly higher mean arterial pressure, arterial pH, serum bicarbonate concentrations, and survival (90% vs. 8%, P = .005) than did rabbits challenged with LOS alone. Relative to untreated controls, rabbits pretreated with LALF intravenously (iv) at 1.2 mg/kg (n = 21) also had significant improvements in physiologic measurements and higher survival (52% vs. 8%, P = .003). Even when LALF (1.2 mg/kg iv) was given 1/2 h after LOS challenge, animals showed significant improvements in physiologic measurements and survival (33% vs. 8% in untreated controls P = .028). LALF-treated animals also had significantly lower circulating endotoxin activity and tumor necrosis factor concentrations. Thus, LALF attenuates the toxic effects of meningococcal LOS in rabbits even when administered after LOS challenge and deserves further evaluation as a potential therapeutic agent for treating gram-negative septic shock.
Alpert
G
G
Department of Medicine (Division of Emergency Medicine), Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Baldwin
G
G
Thompson
C
C
Wainwright
N
N
Novitsky
T J
TJ
Gillis
Z
Z
Parsonnet
J
J
Fleisher
G R
GR
Siber
G R
GR
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D000925:Anticoagulants / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D001639:Bicarbonates / Q000097:blood; D001794:Blood Pressure; D004195:Disease Models, Animal; D004731:Endotoxins / Q000276:immunology; D006737:Horseshoe Crabs; D006863:Hydrogen-Ion Concentration; D007447:Invertebrate Hormones / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008589:Meningococcal Infections / Q000188:drug therapy / Q000517:prevention & control*; D011817:Rabbits; D012772:Shock, Septic / Q000188:drug therapy / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000890:Anti-Infective Agents; D000925:Anticoagulants; D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D001639:Bicarbonates; D004731:Endotoxins; D007447:Invertebrate Hormones; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C034705:antilipopolysaccharide factor (Limulus); C023023:lipid-linked oligosaccharides