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

P Matzneller1, S Strommer1, C Drucker1

  • 1Department of Clinical Pharmacology, Medical University of Vienna, Austria.

Clinical Pharmacology and Therapeutics
|November 20, 2016
PubMed
Summary
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Colistin, an antibiotic, was investigated for its anti-endotoxin effects in humans. This study confirmed colistin significantly reduces the inflammatory response to lipopolysaccharide (LPS) in healthy volunteers.

Area of Science:

  • Pharmacology
  • Immunology
  • Clinical Trials

Background:

  • The anti-endotoxin properties of colistin are well-documented in preclinical studies.
  • However, its effects on human inflammatory responses in vivo remained uninvestigated.

Purpose of the Study:

  • To evaluate the in vivo anti-endotoxin effect of colistin in a human endotoxemia model.
  • To determine colistin's modulation of inflammatory biomarkers following lipopolysaccharide (LPS) challenge.

Main Methods:

  • A randomized, double-blind, placebo-controlled crossover trial was conducted.
  • Healthy volunteers received a single intravenous dose of colistin methanesulfonate.
  • Inflammatory markers including cytokines (IL-6, IL-8, TNF-α, IL-1β), C-reactive protein, leukocyte counts, and body temperature were measured up to 24 hours post-dose.

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Main Results:

  • Colistin significantly attenuated the inflammatory cytokine response induced by LPS.
  • The most pronounced effects were observed for interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α).
  • Colistin demonstrated a significant reduction in key inflammatory biomarkers.

Conclusions:

  • This study provides the first in vivo confirmation of colistin's anti-endotoxin effect in humans.
  • Colistin effectively modulates the inflammatory cascade triggered by LPS.
  • Further research is warranted to elucidate the intricate interactions between colistin and immune system effectors.