Propylene-glycol aggravates LPS-induced sepsis through production of TNF-α and IL-6

Iran J Immunol. 2014 Jun;11(2):113-22.


Background: Propylene glycol (1,2-propanediol, PG) is a commonly used solvent for oral, intravenous, as well as topical pharmaceutical preparations. While PG is generally considered to be safe, it has been known that large intravenous doses given over a short period of time can be toxic.

Objective: To evaluate the effect of PG in sepsis induced by the bacterial endotoxin lipopolysaccharide (LPS).

Methods: Balb/c mice were treated with LPS (1 mg/kg b.w., i.p.) with or without PG (5 g/kg b.w. i.v.). The survival rate and the production of inflammatory cytokines were measured. In RAW264.7 mouse macrophages encoding NF-kB-luc reporter gene, the nuclear transcription factor kappa-B (NF-kB) activation was measured.

Results: We found that intravenous PG increased the mortality rate in sepsis induced by the bacterial endotoxin lipopolysaccharide (LPS) in mice. In accordance with that, PG enhanced LPS-induced production of inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in vivo. PG also increased the LPS-induced macrophage activation in vitro as detected by measuring NF-kB activation.

Conclusion: Our results indicate that drugs containing high doses of PG can pose a risk when administered to patients suffering from or prone to Gram negative bacterial infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cytokines / biosynthesis
  • Cytokines / blood
  • Disease Models, Animal
  • Enzyme Activation
  • Female
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / blood
  • Lipopolysaccharides / adverse effects
  • Lipopolysaccharides / immunology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Mice
  • NF-kappa B / metabolism
  • Propylene Glycol / adverse effects
  • Sepsis / chemically induced
  • Sepsis / immunology
  • Sepsis / metabolism*
  • Sepsis / mortality
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / blood


  • Cytokines
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Propylene Glycol