title: Propylene-glycol aggravates LPS-induced sepsis through production of TNF-α and IL-6.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary, e-mail: marton.annamaria@brc.mta.hu.
authors: Annamaria
authors: A
authors: Marton
authors: Csongor
authors: C
authors: Kolozsi
authors: Erzsebet
authors: E
authors: Kusz
authors: Zoltan
authors: Z
authors: Olah
authors: Tamas
authors: T
authors: Letoha
authors: Csaba
authors: C
authors: Vizler
authors: Laszlo
authors: L
authors: Pecze
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D019946:Propylene Glycol / Q000009:adverse effects; D018805:Sepsis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000097:blood
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019946:Propylene Glycol