Effect of Melatonin on Human Nighttime Endotoxaemia: Randomized, Double-blinded, Cross-over Study

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

10 Citationer (Scopus)


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.

TidsskriftIn vivo (Athens, Greece)
Udgave nummer6
Sider (fra-til)1057-1063
Antal sider7
StatusUdgivet - 16 nov. 2014


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