Effect of melatonin on human nighttime endotoxaemia: randomized, double-blinded, cross-over study.

Mahdi Alamili, Klaus Bendtzen, Jens Lykkesfeldt, Jacob Rosenberg, Ismail Gögenur

Journal: In vivo (Athens, Greece) 2015;28(6):1057-63

PMID: 25398799

Abstract

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.

PATIENTS AND 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.

CONCLUSION

Melatonin has no beneficial effect on inflammation and oxidative damage induced by nighttime endotoxaemia in contrast to daytime endotoxaemia.

Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Address: Department of Surgery, Køge Hospital, University of Copenhagen, Køge, Denmark [email protected].; Institute for Inflammation Research, Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Surgery, Herlev Hospital, University of Copenhagen, Herlev, Denmark.; Department of Surgery, Køge Hospital, University of Copenhagen, Køge, Denmark.

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