Lipopolysaccharide-induced nasal cytokine response: a dose-response evaluation

Information on the dose-response relationship is a prerequisite to defining the non-response threshold of exposure. We investigated whether nasal lipopolysaccharide (LPS) challenges induce an inflammatory response in a dose-dependent way. In three settings nasal lavage was performed before, and 20 min, 1, 6, 23, and 29 h after instillation of 0 microg, 10 microg, and 40 microg LPS for 10 s, in seven healthy subjects. Lavage fluids were analysed for concentrations of interleukin-6 (IL-6), IL-8, tumour necrosis factor-alpha (TNF-alpha), histamine, and albumin. Symptoms were recorded by questionnaire and spirometric lung function was assessed after each lavage. The instillation of 40 microg LPS caused a small increase in nasal symptoms. TNF-alpha was below the detection limit (0.5 pg/ml) in most subjects and, like IL-8 and albumin, showed no relation to the LPS challenge. IL-6 increased over twofold with 10 microg LPS and over 13-fold with 40 microg LPS, with a peak at 6 h after LPS provocation, and the repeated design ANOVA was significant for dose and for time. Six hours after the 40 microg LPS challenge the histamine level significantly increased compared to the saline treatment. We conclude that short-lasting instillation of LPS causes a dose-dependent IL-6 release in the upper airways and minor nasal symptoms.