Effect of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein (rBPI23) on cerebrospinal fluid inflammation induced by endotoxin.
Endotoxin triggers the subarachnoid inflammation of gram-negative meningitis. This study examined the ability of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein (rBPI23) to block endotoxin-induced meningitis in rabbits. Intracisternal (ic) injection of 10-20 ng of meningococcal endotoxin induced high cerebrospinal fluid (CSF) concentrations of tumor necrosis factor (TNF) and CSF pleocytosis and increased CSF lactate concentrations. ic administration of rBPI23 significantly reduced meningococcal endotoxin-induced TNF release into CSF (P < .005), lactate concentrations (P < .001), and CSF white blood cell counts (P < .01). No such effect was observed in animals receiving intravenous rBPI23. Concentrations of rBPI23 in CSF were high after ic administration but low or undetectable after systemic administration. Thus, high concentrations of rBPI23 can effectively neutralize meningococcal endotoxin in CSF, but low CSF concentrations after systemic administration currently limit its potential usefulness as adjunctive drug treatment in gram-negative meningitis.
Kartalija
M
M
Infectious Diseases Laboratory, San Francisco General Hospital, California.
Kim
Y
Y
White
M L
ML
Nau
R
R
Tureen
J H
JH
Täuber
M G
MG
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D002555:Cerebrospinal Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D007773:Lactates / Q000134:cerebrospinal fluid; D019344:Lactic Acid; D008565:Membrane Proteins; D008585:Meningitis, Meningococcal / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D009345:Neisseria meningitidis; D010446:Peptide Fragments / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000627:therapeutic use; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D004731:Endotoxins; D007773:Lactates; D008565:Membrane Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C021623:bactericidal permeability increasing protein; D019344:Lactic Acid