Propylene-Glycol Aggravates LPS-Induced Sepsis through Production of TNF-alpha and IL-6

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-kappa B-luc reporter gene, the nuclear transcription factor kappaB (NF-kappa B) 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-a (TNF-alpha) and interleukin-6 (IL-6) in vivo. PG also increased the LPS-induced macrophage activation in vitro as detected by measuring NF-kappa B 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.