EFFECT OF A RECOMBINANT N-TERMINAL FRAGMENT OF BACTERICIDAL/PERMEABILITY-INCREASING PROTEIN (RBPI(23)) 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 (rBPI(23)) 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 rBPI(23) 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 rBPI(23), Concentrations of rBPI(23) in CSF were high after ic administration but low or undetectable after systemic administration, Thus, high concentrations of rBPI(23) 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.