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

Abstract

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 10⁸ colony-forming units of Escherichia coli in 100 μl 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-α 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.

Comparison of the performance of targeted mitochondrial antioxidant mitoquinone and non-targeted antioxidant pentoxifylline in improving rooster sperm parameters during freezing and thawing

“…PTX increases cAMP levels in the cell by inhibiting the phosphodiesterase enzyme. This increase leads to ATP enhancement, which in turn results in cellular glycolysis, energy production, increased sperm motility, and increased ATP production ( Park et al, 2000 ), which can be satisfactory explanation for the results in the present study. The present results affirm that adding PTX to the extender could increase progressive motility before cryopreservation.…”

Tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 in the cerebrospinal fluid of newborn with meningitis

“…The brain of the newborn, in a phase of accelerated growth, contains high concentrations of polyunsaturated fatty acids, thus is particularly suscepti- ble to the lesion induced by O 2 free radicals. In addition, these factors coincide also with the fact that the lowest levels of oxygen free radical scavengers and antioxidant enzymes are occurring in the neonatal period 12 . Experimental studies have demonstrated the sequential emergence of the bioactivity of TNF-α, IL-1β and IL-6 in CSF after injection of PLS or viable meningococci in the subarachnoid space 13 .…”

“…Experimental studies have demonstrated the sequential emergence of the bioactivity of TNF-α, IL-1β and IL-6 in CSF after injection of PLS or viable meningococci in the subarachnoid space 13 . Probably the increase of the production of TNF-α at the beginning of the inflammatory reaction 12,14 induces the secretion of IL-1β, both cytokines being responsible for the first steps of the inflammation cascade that leads to the destruction of tissue.…”

Reprogramming the Host Response in Bacterial Meningitis: How Best To Improve Outcome?

“…Degradation of intracellular cAMP can be inhibitid by phosphodiesterase inhibitors, such as the type IV phosphodiesterase inhibitor rolipram. In addition, the phophodiesterase inhibitor pentoxifylline (a methylxanthine derivative) reduced inflammation in the subarachnoid space in several models of bacte- rial meningitis but had no significant effect on blood-brain barrier permeability or neuronal damage (106,133,175). New xanthine derivatives such as lisofylline, which have a similar mode of action, are less toxic, making their clinical use more feasible (165).…”