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

Abstract

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 endotoxemia model. After a single intravenous dose of 2.5 million IU colistin methanesulfonate, interleukin (IL)-6, IL-8, tumor necrosis factor alpha (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 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-α. 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.

Induction of the pneumococcal vncRS operon by lactoferrin is essential for pneumonia

“…Chromosomal DNA was detected in the supernatants after infection with WT bacteria 4 h post-injection, whereas negligible or no chromosomal DNA was detected in the supernatant after infection with Δpep27 , suggesting that this mutant is not capable to induce lysis and hence no chromosomal DNA could be detected in supernatant (Figure 3(g)), indicating that the Δpep27 cells were rapidly cleared. Since the proinflammatory cytokines produced within 6 h post-infection play a critical role in septic shock [18–21], the lysis-resistance of bacterial cells was corroborated by measuring the proinflammatory cytokines 6 h after i.n . infection.…”

Antibiotic efficacy varies based on the infection model and treatment regimen for Pseudomonas aeruginosa

“…Although the efficacy of TOB was greater than that of COL in reducing bacterial burden in the acute infection model, COL significantly reduced the inflammatory profile in the airways, particularly the neutrophil load, and to a moderately greater extent than by TOB. This may reflect the contribution of immunomodulatory effects of antibiotics to efficacy [32,33] and deserves further investigation with additional model systems. Assessment of cytokine/chemokine profiles revealed significantly reduced levels of G-CSF and KC in mice treated with TOB and COL by local and systemic administration.…”

PCSK9 decreases during experimental endotoxemia

“…We analysed PCSK9 levels in two distinct populations: study I examined experimental endotoxemia in healthy volunteers, and study II investigated critically ill patients in medical intensive care units. In study I, we investigated PCSK9 levels in the human endotoxemia model, which is an in vivo model of an acute, self-limiting, inflammatory response with an intertwined activation of coagulation provoked by a bolus infusion of LPS [7]. Whilst in clinical studies the earliest possible assessment is usually triggered by clinical signs and symptoms of infection or sepsis, this model also allows investigation of the preceding period.…”

“…The analysed plasma samples were taken from the placebo period of a double-blind, randomized, crossover trial (n = 16) [7]. At baseline, PCSK9 levels were 199 AE 57 ng mL À1 (mean AE standard deviation).…”