Efficacy of Anti-Tumor Necrosis Factor-Alpha Antibody as an Adjunctive Therapy in Experimental <i>Escherichia coli</i> Meningitis in the Newborn Piglet

Abstract

This study was done to evaluate the efficacy of anti-tumor necrosis factor alpha (anti-TNF-α) antibody as an adjunctive therapy in neonatal bacterial meningitis. Newborn piglets were divided into three groups: 8 in the control group, 13 in the meningitis group (MG), and 10 in the meningitis with anti-TNF-α antibody group (AG). Meningitis was induced by intracisternal injection of 10⁸ colony-forming units of Escherichia coli in 100 μl of saline. In the AG, 200 μl of anti-TNF-α antibody was also given intracisternally. In the AG, the elevated cerebrospinal fluid TNF-α level observed in the MG was completely abolished, and increased intracranial pressure, hypoglycorrhachia, and CSF pleocytosis observed in the MG were downmodulated. But blood, brain, and CSF lactate levels remained elevated in both MG and AG. Increased brain cell membrane lipid peroxidation products and decreased Na⁺,K⁺-ATPase activity observed in the MG were not attenuated in the AG. These results indicate that anti-TNF-α antibody was not particularly effective as an adjunctive therapy in attenuating acute inflammatory responses and ameliorating brain damage in neonatal bacterial meningitis.

The Efficacy of Pentoxifylline as an Anti-Inflammatory Agent in Experimental <i>Escherichia coli</i> Meningitis in the Newborn Piglet

“…However, in our previous [37] and present studies, although we were able to block the increased TNF-· concentration in the CSF by administering anti-TNF-· antibody or pentoxifylline, meningeal inflammatory responses were not particularly down-modulated. In our another previous study [25], although induced hyperglycemia significantly attenuated the inflammatory responses of meningitis, CSF TNF-· level was not downmodulated.…”

7-Nitroindazole, but Not Aminoguanidine, Attenuates the Acute Inflammatory Responses and Brain Injury during the Early Phase of <i>Escherichia coli</i> Meningitis in the Newborn Piglet

“…In the present study, aminoguanidine, but not 7-nitroindazole, significantly attenuated the meningitis-induced increase in the CSF TNF-· level, suggesting a positive regulatory link between iNOS and TNF-· in bacterial meningitis. However, since the inflammatory responses were not attenuated with aminoguanidine treatment, the role of TNF-· in mediating the acute inflammation during bacterial meningitis might not be essential [25].…”

“…A well-characterized newborn piglet model of neonatal bacterial meningitis described previously in detail [24][25][26] was used in this study. Briefly, newborn piglets less than 3 days old were anesthetized with sodium thiopental (5 mg/kg i.v.…”

Enhancement of Neonatal Innate Defense: Effects of Adding an N-Terminal Recombinant Fragment of Bactericidal/Permeability-Increasing Protein on Growth and Tumor Necrosis Factor-Inducing Activity of Gram-Negative Bacteria Tested in Neonatal Cord Blood Ex Vivo

“…5). Excessive TNF release has been implicated in the pathophysiology of neonatal septic shock (23), and agents that reduce TNF-␣ release have been shown to have beneficial effects in newborn animal models of gram-negative infection in vivo (9,25). In contrast, the tendency to have low ex vivo TNF production in response to endotoxin challenge increases the risk of fatal bacterial infection (35).…”