Effect of melatonin on human nighttime endotoxaemia: randomized, double-blinded, cross-over study.
BACKGROUND
Endotoxaemia is widely used as an experimental model to study sepsis under controlled conditions. Nighttime endotoxaemia induces a more pronounced inflammatory stress response compared to daytime. Previously, we have shown that melatonin has antioxidative and anti-inflammatory effects in inflammatory response to daytime endotoxaemia. Herein, we examined the effect of melatonin in response to human nighttime endotoxaemia.


METHODS
Twelve healthy male volunteers were enrolled in a randomized, placebo-controlled, double-blinded cross-over trial. Subjects were induced by lipopolysaccharide (LPS) endotoxin 0.3 ng/kg body weight intravenously at 24:00. One hour prior to induction of endotoxaemia, an 8-h infusion of melatonin 100 mg or placebo was initiated. Blood samples were drawn before and 2, 4, 6 and 8 h after induction of endotoxaemia and plasma was tested for pro-inflammatory markers (tumor necrosis factor alpha, TNF-α, interleukin-1β, IL-1β, interleukin-1, IL-6, and YKL-40), anti-inflammatory markers (interleukin-1 receptor antagonist, IL-1Ra, interleukin-10, IL-10, soluble tumor necrosis factor receptors I and II, sTNF-RI and sTNF-RII), marker for oxidative damage (malondialdehyde (MDA)) and antioxidative enzyme (ascorbic acid (AA) and dehydroascorbic acid (DHA)).


RESULTS
Compared to placebo, melatonin did not reduce plasma levels of any of pro- and anti-inflammatory markers and it also failed to influence levels of AA, DHA and MDA.


CONCLUSIONS
Melatonin has no beneficial effect on inflammation and oxidative damage induced by nighttime endotoxaemia in contrast to daytime endotoxaemia.
Department of Surgery, Køge Hospital, University of Copenhagen, Køge, Denmark mahdi_alamili@hotmail.com.
Mahdi
M
Alamili
Institute for Inflammation Research, Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Klaus
K
Bendtzen
Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jens
J
Lykkesfeldt
Department of Surgery, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Jacob
J
Rosenberg
Department of Surgery, Køge Hospital, University of Copenhagen, Køge, Denmark.
Ismail
I
Gögenur
D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D015415:Biomarkers; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004311:Double-Blind Method; D055870:Drug Chronotherapy; D019446:Endotoxemia / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D013997:Time Factors; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D008550:Melatonin
Melatonin; endotoxaemia; human; inflammation; oxidative damage; oxidative stress; sepsis