Immune-modulating effects of melatonin, N-acetylserotonin, and N-acetyldopamine

Ann N Y Acad Sci. 2005 Aug:1053:386-93. doi: 10.1111/j.1749-6632.2005.tb00046.x.

Abstract

Melatonin and N-acetylserotonin (NAS) have antioxidant properties. In the present study, we examined whether melatonin, NAS, and N-acetyldopamine (NAD) have a modulatory effect on tumor necrosis factor-alpha (TNF-alpha) synthesis and superoxide production. Differentiated THP-1-derived human monocytes were coincubated with Escherichia coli lipopolysaccharide (LPS) and rising concentrations of melatonin, NAS, or NAD. After 24 h, TNF-alpha was measured in cell supernatants. In addition, the production of superoxide by HL-60-derived human neutrophils upon stimulation with 4-beta-phorbol 12-beta-myristate 13-alpha-acetate (PMA) or N-formyl methionyl-leucyl-phenylalanine (fMLP) and increasing concentrations of melatonin, NAS, or NAD was determined. Incubation of THP-1-derived monocytes with increasing concentrations of melatonin, NAS, or NAD resulted in a marked decrease in LPS-stimulated TNF-alpha production, which was dose-dependent and on the order of 96-98%. Incubation of HL-60-derived neutrophils with increasing concentrations of melatonin, NAS, or NAD resulted in a modest decrease in PMA-stimulated superoxide production, which was dose-dependent. At the 100 microM dose, melatonin, NAS, or NAD resulted in a 14 +/- 4%, 30 +/- 1%, and 29 +/- 1% decrease in PMA-stimulated superoxide production, respectively. Coincubation of HL-60 cells with melatonin, NAS, or NAD also resulted in a modest dose-dependent decrease in fMLP-stimulated superoxide production. At the 100 microM dose, melatonin, NAS, or NAD resulted in a 13 +/- 1%, 14 +/- 1%, and 14 +/- 1% decrease in superoxide production, respectively. Our results indicate that the inhibitory effect of melatonin, NAS, or NAD on LPS-induced TNF-alpha production is robust and dose-dependent. These compounds are equally effective in attenuating the generation of oxidant radicals, although to a lesser degree.

MeSH terms

  • Antioxidants / pharmacology*
  • Cell Line
  • Cytokines / biosynthesis
  • Dopamine / analogs & derivatives*
  • Dopamine / pharmacology
  • HL-60 Cells
  • Humans
  • Immunologic Factors*
  • Melatonin / pharmacology*
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Serotonin / analogs & derivatives*
  • Serotonin / pharmacology
  • Superoxides / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Antioxidants
  • Cytokines
  • Immunologic Factors
  • Tumor Necrosis Factor-alpha
  • Superoxides
  • N-acetyldopamine
  • Serotonin
  • Melatonin
  • Tetradecanoylphorbol Acetate
  • N-acetylserotonin
  • Dopamine