Effects of polymyxin-B on TNF-α production in equine whole blood stimulated with three different bacterial toxins

J Vet Pharmacol Ther. 2018 Feb;41(1):e35-e39. doi: 10.1111/jvp.12445. Epub 2017 Aug 14.

Abstract

Polymyxin-B is used to treat equine systemic inflammation. Bacterial toxins other than lipopolysaccharide (LPS) contribute to systemic inflammation but the effects of polymyxin-B on these are poorly defined. Whole blood aliquots from six healthy horses diluted 1:1 with RPMI were incubated for 21 hr with 1 μg/ml of LPS, lipoteichoic acid (LTA) or peptidoglycan (PGN) in the presence of increasing concentrations of polymyxin-B (10-3000 μg/ml). A murine L929 fibroblast bioassay was used to measure TNF-α activity. Polymyxin-B significantly inhibited the effects of all three bacterial toxins. Analysis of variance showed the IC50 value for polymyxin-B for TNF-α inhibition caused by LTA (11.19 ± 2.89 μg/ml polymyxin-B) was significantly lower (p = .009) than the values for LPS (46.48 ± 9.93 μg/ml) and PGN (54.44 ± 8.97 μg/ml). There was no significant difference in IC50 values between LPS and PGN (p > .05). Maximum inhibition of TNF-α was 77.4%, 73.0% and 82.7% for LPS, PGN and LTA, respectively and was not significantly different between toxins. At the two highest concentrations of polymyxin-B, TNF-α began to increase. These data suggest that polymyxin-B may inhibit the effects of bacterial toxins other than LPS and might be a more potent inhibitor of LTA than LPS or PGN.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Toxins / antagonists & inhibitors
  • Bacterial Toxins / pharmacology*
  • Dose-Response Relationship, Drug
  • Horses / blood
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Peptidoglycan / pharmacology*
  • Polymyxin B / administration & dosage
  • Polymyxin B / pharmacology*
  • Teichoic Acids / antagonists & inhibitors
  • Teichoic Acids / pharmacology*
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Toxins
  • Lipopolysaccharides
  • Peptidoglycan
  • Teichoic Acids
  • Tumor Necrosis Factor-alpha
  • lipoteichoic acid
  • Polymyxin B