title: Immune-modulating effects of melatonin, N-acetylserotonin, and N-acetyldopamine.
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.
authors.affiliation: Division of Nephrology, Department of Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, 736 Cambridge Street, Boston, Massachusetts 02135, USA.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Perianayagam
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Oxenkrug
authors.forename: Bertrand L
authors.initials: BL
authors.lastname: Jaber
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007155:Immunologic Factors; D008550:Melatonin / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000975:Antioxidants; D016207:Cytokines; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; C006374:N-acetyldopamine; D012701:Serotonin; D008550:Melatonin; D013755:Tetradecanoylphorbol Acetate; C006389:N-acetylserotonin; D004298:Dopamine