Lipofundin Mediates the Major Inhibition of Intravenous Propofol in IL-1β Secretion and Phagocytosis of Staphylococcus aureus-Infected Macrophages

Lipids. 2020 Jan;55(1):45-52. doi: 10.1002/lipd.12207. Epub 2019 Dec 15.

Abstract

Lipofundin is the solvent for propofol in the intravenous injection of Propofol-Lipuro® and is used in patients who need intravenous feeding to provide fatty acids and fat for energy. In addition to propofol, Lipofundin also affects the immune modulation of phagocytes. In a previous study, we reported that intravenous propofol effectively decreased Staphylococcus aureus-stimulated reactive oxygen species (ROS) levels, IL-1β secretion, and phagocytosis in RAW264.7 macrophages. It is important to separately assess the effects of pure propofol, Lipofundin, and Propofol-Lipuro. By using an S. aureus-infected RAW264.7 macrophage model, the levels of secreted IL-1β in cell supernatants were determined by ELISA. IL-1β mRNA in cell pellets was further analyzed by quantitative polymerase chain reaction (qPCR), and Western blotting was performed to detect pro-IL-1β synthesis. Total ROS levels were determined by a luminol chemiluminescence assay. Compared with pure propofol, treatment with clinically relevant concentrations of Propofol-Lipuro and Lipofundin obviously reduced IL-1β secretion (>85% inhibition), S. aureus-stimulated ROS production (50% inhibition), and phagocytosis (>60% inhibition) to similar levels. Treatment with pure propofol alone significantly decreased IL-1β mRNA levels and pro-IL-1β protein synthesis, and slightly inhibited phagocytosis. In contrast, treatment with Propofol-Lipuro did not influence IL-1β mRNA or pro-IL-1β protein expression, even though treatment with Lipofundin increased the levels of both IL-1β mRNA and its precursor protein. In conclusion, IL-1β secretion is regulated at the posttranslational level. Lipofundin mediated the major effect of Propofol-Lipuro on the inhibition of IL-1β secretion, ROS production, and phagocytosis in S. aureus-infected RAW264.7 cells.

Keywords: S. aureus; IL-1β; Lipofundin; Propofol; Propofol-Lipuro®; RAW264.7 macrophage.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Animals
  • Down-Regulation
  • Drug Combinations
  • Gene Expression Regulation / drug effects
  • Interleukin-1beta / genetics*
  • Interleukin-1beta / metabolism*
  • Macrophages / cytology
  • Macrophages / immunology
  • Macrophages / microbiology*
  • Mice
  • Phagocytosis / drug effects
  • Phospholipids / pharmacology*
  • Propofol / pharmacology*
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism
  • Sorbitol / pharmacology*
  • Staphylococcus aureus / immunology*

Substances

  • Drug Combinations
  • IL1B protein, mouse
  • Interleukin-1beta
  • Phospholipids
  • Reactive Oxygen Species
  • Lipofundin
  • Sorbitol
  • Propofol