The efficacy of pentoxifylline as an anti-inflammatory agent in experimental Escherichia coli meningitis in the newborn piglet.
This study was done to evaluate the anti-inflammatory effect and the ensuing neuroprotective effect of pentoxifylline in neonatal experimental bacterial meningitis. Newborn piglets were divided into three groups: 10 in the control group (CG), 13 in the meningitis group (MG), and 13 in the meningitis with pentoxifylline group (PG). Meningitis was induced by intracisternal injection of 10(8) colony-forming units of Escherichia coli in 100 microl of saline. In PG, 20 mg/kg of pentoxifylline was given as a bolus intravenous injection 30 min before induction of meningitis and 6 mg/kg/h was given continuously throughout the experiment. In PG, the increase of CSF TNF-alpha level observed in MG was abolished. Reduced brain glucose and ATP concentrations observed in MG were significantly increased in PG. However, other parameters of inflammatory responses such as increased intracranial pressure, reduced glucose and increased lactate concentrations in the CSF observed in MG were not significantly down-modulated. The extent of CSF leukocytosis was even higher in PG than in MG. Increased cerebral cortical cell membrane lipid peroxidation products and decreased Na(+),K(+)-ATPase activity observed in MG, indicative of meningitis-induced brain cell membrane dysfunction, tended to improve without statistical significance in PG. In summary, although some anti-inflammatory effects have been observed, the overall anti-inflammatory effects of pentoxifylline was very weak, and it failed to significantly reduce the brain damage in experimental neonatal bacterial meningitis.
Park
W S
WS
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. wspark@smc.samsung.co.kr
Chang
Y S
YS
Lee
M
M
D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000382:microbiology; D015169:Colony Count, Microbial; D004927:Escherichia coli Infections / Q000382:microbiology; D005947:Glucose / Q000134:cerebrospinal fluid; D019344:Lactic Acid / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D007958:Leukocyte Count; D016920:Meningitis, Bacterial / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000378:metabolism; D010431:Pentoxifylline / Q000627:therapeutic use*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D005947:Glucose; D010431:Pentoxifylline