Colistin reduces LPS-triggered inflammation in a human sepsis model in vivo: A randomized controlled trial

Objectives: The previously described anti-endotoxin effect of colistin was not investigated in humans yet. We performed a randomized, double-blind, placebo-controlled crossover trial to determine the degree of colistin-driven modulation of inflammatory response in blood of lipopolysaccharide (LPS) - challenged healthy volunteers in a human endotoxemia model. Methods: After a single intravenous dose of 2.5 million IU colistin methanesulfonate, IL-6, IL-8, TNF-α and IL-1β concentrations as well as other biomarkers of inflammation such as C-reactive protein, differential leukocyte counts and body temperature were measured up to 24 hours post-dose. Results: Colistin significantly decreased the inflammatory cytokine response to LPS in blood of healthy volunteers. This effect was most evident for IL-6, IL-8 and TNF-α. Conclusions: This study is the first to confirm the anti-endotoxin effect of colistin in humans in vivo. Further studies might increase our knowledge on the interaction between colistin and the effectors of the immune system. This article is protected by copyright. All rights reserved.