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 meni ngitis, This study examined the ability of a recombinant N-terminal fr agment of bactericidal/permeability increasing protein (rBPI(23)) to b lock endotoxin-induced meningitis in rabbits, Intracisternal (ic) inje ction of 10-20 ng of meningococcal endotoxin induced high cerebrospina l fluid (CSF) concentrations of tumor necrosis factor (TNF) and CSF pl eocytosis 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 wh ite 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 a dministration, Thus, high concentrations of rBPI(23) can effectively n eutralize meningococcal endotoxin in CSF, but low CSF concentrations a fter systemic administration currently limit its potential usefulness as adjunctive drug treatment in gram-negative meningitis.