Platelet-activating factor augments meningeal inflammation elicited by Haemophilus influenzae lipooligosaccharide in an animal model of meningitis.
Research into the pathophysiology of bacterial meningitis has suggested a role for various endogenous inflammatory mediators, such as platelet-activating factor (PAF). In the present study, rats were inoculated intracisternally with various doses of PAF, with Haemophilus influenzae lipooligosaccharide (LOS) in high doses (20 ng) alone, and with a low dose of LOS (200 pg) with or without low doses of PAF (25 ng to 2.5 micrograms). Values for cerebrospinal fluid leukocytosis and percent blood-brain barrier permeability to systemically administered 125I-labeled albumin observed after inoculation of low-dose LOS with PAF were greater (P < 0.05) than those observed after inoculation of low-dose LOS alone and not statistically different from those observed after inoculation of high-dose LOS. PAF alone elicited an inflammatory response only at high doses (25 micrograms). These results support the hypothesis that low cerebrospinal fluid PAF concentrations, such as those observed in children with bacterial meningitis, may augment the inflammatory response to the presence of bacteria in the subarachnoid space.
Townsend
G C
GC
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
Scheld
W M
WM
D000818:Animals; D001812:Blood-Brain Barrier; D004195:Disease Models, Animal; D005260:Female; D008070:Lipopolysaccharides / Q000633:toxicity*; D008583:Meningitis, Haemophilus / Q000134:cerebrospinal fluid / Q000209:etiology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; C023023:lipid-linked oligosaccharides