propylene-glycol aggravates lps-induced sepsis through production of tnf-α 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- b-luc reporter gene, the nuclear transcription factor kappa- b (nf- 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-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- 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.