Inhaled LPS challenge in healthy subjects: a dose escalation study

Abstract

Background: Lipopolysaccharide (LPS) inhalation causes rapid activation of the innate immune response and has been used as an experimental model of acute neutrophilic lung disease. Previous studies have used various LPS doses making it difficult to compare results due to the potential variability in biological response. Aims and Objectives: We used LPS produced to Good Manufacturing Practice standards to characterise the dose response to a standardised inhalation material in healthy subjects. Methods: 15 healthy non-smoking subjects inhaled 5, 15 and 50µg LPS. Whole blood cell counts, serum CRP, sputum cell counts and sputum IL-1β, IL-6 and TNFα levels were measured at baseline and post-LPS. Results: LPS inhalation with all doses was well tolerated. Blood neutrophil count was significantly increased at 6 hours post-LPS with all doses, while CRP increased with 15µg and 50µg LPS. Sputum neutrophils increased with all LPS doses and levels of IL-1β, IL-6 and TNFα all increased with 50µg LPS (Table 1). Data: mean (SEM) Baseline V post-LPS *p Conclusions: Inhaled GMP grade LPS was well tolerated and caused a dose response effect in healthy volunteers. The lower doses of LPS caused neutrophilic inflammation but generally the effects on other biomarkers were much less consistent. Challenge with 50µg GMP grade LPS induced significant inflammation in the lungs and circulation and we propose that this dose should be used in future challenge studies.