title: Melatonin suppresses markers of inflammation and oxidative damage in a human daytime endotoxemia model.
abstract: OBJECTIVE
  Melatonin used as an exogenous drug has been documented to have potent antioxidant and anti-inflammatory effects in animal model. We aimed to examine the effect of melatonin in an experimental human sepsis model.
  
  
  METHODS
  Twelve healthy males were enrolled in a randomized, placebo-controlled, double-blinded cross-over trial. They received lipopolysaccharide endotoxin 0.3 ng/kg of body weight intravenously at 12:00. Before endotoxemia, an 8-hour infusion of melatonin (100 mg) or placebo (saline) was initiated. Blood samples were drawn before and at 2, 4, 6, and 8 hours after lipopolysaccharide administration. Proinflammatory (tumor necrosis factor α [TNF-α], interleukin [IL] 1β, IL-6, and YKL-40), anti-inflammatory markers (IL-1Ra, IL-10, soluble tumor necrosis factor receptor I, and soluble tumor necrosis factor receptor II), a marker for oxidative damage (malondialdehyde), and antioxidants (ascorbic acid and dehydroascorbic acid) were analyzed in plasma.
  
  
  RESULTS
  Melatonin significantly reduced proinflammatory markers IL-1β (P < .01) and YKL-40 (P < .05) but not TNF-α and IL-6. None of the anti-inflammatory markers (IL-1Ra, IL-10, soluble tumor necrosis factor receptor I, and soluble tumor necrosis factor receptor II) were lowered by melatonin. Melatonin reduced the levels of ascorbic acid (P < .05) but not dehydroascorbic acid or malondialdehyde.
  
  
  CONCLUSIONS
  Melatonin administration before endotoxemia resulted in reduction of certain markers of inflammation and oxidative stress. Further studies are needed to clarify the role of melatonin in clinical setting.
authors.affiliation: Department of Surgical Gastroenterology, University of Copenhagen, Herlev Hospital, Denmark. Electronic address: mahdi_alamili@hotmail.com.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Alamili
authors.affiliation: Institute for Inflammation Research, Department of Rheumatology, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
authors.affiliation: Department of Surgical Gastroenterology, University of Copenhagen, Herlev Hospital, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Rosenberg
authors.affiliation: Department of Surgical Gastroenterology, University of Copenhagen, Herlev Hospital, Denmark.
authors.forename: Ismail
authors.initials: I
authors.lastname: Gögenur
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers; D018592:Cross-Over Studies; D016207:Cytokines / Q000378:metabolism; D004311:Double-Blind Method; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D008315:Malondialdehyde; D008550:Melatonin
keywords: Endotoxemia; Human; Inflammation; Melatonin; Oxidative damage; Oxidative stress; Sepsis