Secretion of tumor necrosis factor by endotoxin-treated equine mammary exudate macrophages: effect of dexamethasone and pentoxifylline.

The study investigates the secretion of tumor necrosis factor (TNF) by equine mammary exudate macrophages (MEM phi) when exposed to bacterial lipopolysaccharide (LPS) and the effects of dexamethasone and pentoxifylline on this process. It was found that dexamethasone and pentoxifylline significantly inhibit TNF production when applied before or up to several hours after LPS exposure, this inhibition was not due to reduced macrophage viability or interference at the TNF bioassay level.

Research Methods

• The research involved exposing equine mammary exudate macrophages (MEM phi) to different concentrations of bacterial lipopolysaccharide (LPS) and measuring the secretion of tumor necrosis factor (TNF).
• Various concentrations of dexamethasone were tested for their effects on TNF production by MEM phi when added an hour before LPS.
• The effect of pretreatment with pentoxifylline at concentrations greater than 3 micrograms/ml on TNF secretion by MEM phi was also assessed.

Key Findings

• Tumor necrosis factor secretion was found to be dose-dependent on LPS exposure
• All concentrations of dexamethasone tested significantly inhibited TNF production when added an hour before LPS exposure.
• Pretreatment with pentoxifylline also significantly reduced TNF secretion.

Further Observations

• The inhibitory effect of dexamethasone was observed from 30 minutes before until 4 hours after LPS exposure.
• Pentoxifylline suppressed TNF production when added from 2 hours before until 2 hours after LPS exposure. However, when the addition was delayed until 8 hours post-LPS, TNF production was enhanced.
• The inhibitory effects observed from both dexamethasone and pentoxifylline were not due to reduced macrophage viability or interference at the TNF bioassay level.

Implications

• The study provides insights into the mechanisms of TNF production during a bacterial infection and highlights regulators of this process, potentially pointing to new therapeutic targets for certain conditions.
• The findings also suggest that timing of dexamethasone and pentoxifylline administration could be crucial in modulating the immune response, with late administration of pentoxifylline potentially having the opposite effect.