Melatonin suppresses markers of inflammation and oxidative damage in a human daytime endotoxemia model

Purpose: 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. Materials and 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 alpha[TNF-alpha], interleukin [IL] 1 beta, IL-6, and YKL-40), anti-inflammatorymarkers (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-1 beta (P < .01) and YKL-40 (P < .05) but not TNF-alpha 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. (C) 2014 Elsevier Inc. All rights reserved.