title: 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.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Matzneller
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Strommer
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Drucker
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Petroczi
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Schörgenhofer
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Lackner
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Jilma
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Zeitlinger
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001833:Body Temperature Regulation / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D003091:Colistin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D064368:Healthy Volunteers; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000097:blood; D007262:Infusions, Intravenous; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D018805:Sepsis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D002097:C-Reactive Protein; D003091:Colistin