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

Abstract

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