Colistin Reduces LPS-Triggered Inflammation in a Human Sepsis Model In Vivo: A Randomized Controlled Trial

The previously described anti-endotoxin effect of colistin has not been 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 endotoxemiamodel. After a single intravenous dose of 2.5million IU colistinmethanesulfonate, interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-a), and IL-1b concentrations as well as other biomarkers of inflammation such as C-reactive protein, differential leukocyte counts, and body temperature weremeasured up to 24 h postdose. 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-a. This study is the first to confirm the anti-endotoxin effect of colistin in humans in vivo. Further studiesmight increase our knowledge on the interaction between colistin and the effectors of the immune system.