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

Abstract

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 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: Mahdi Alamili, Klaus Bendtzen, Jens Lykkesfeldt, Jacob Rosenberg, Ismail Gögenur
• Journal: Journal of critical care (J Crit Care) Vol. 29 Issue 1 Pg. 184.e9-184.e13 (Feb 2014) ISSN: 1557-8615 [Electronic] United States
• PMID: 24140166 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Antioxidants
• Biomarkers
• Cytokines
• Inflammation Mediators
• Malondialdehyde
• Melatonin

Topics

• Adult
• Antioxidants (metabolism)
• Biomarkers
• Cross-Over Studies
• Cytokines (metabolism)
• Double-Blind Method
• Humans
• Inflammation Mediators (metabolism)
• Male
• Malondialdehyde (metabolism)
• Melatonin (pharmacology)
• Models, Biological
• Oxidative Stress (drug effects)
• Young Adult