Effects and mechanisms of melatonin on immune responses in mice of different months

Acta Pharmacol Sin. 2003 Jul;24(7):719-23.

Abstract

Aim: To study the effects and mechanisms of melatonin (MT) on immune responses in mice of different months.

Methods: Thymocyte proliferation and IL-2 activity were assayed by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) and activated mouse splenocyte proliferation methods, respectively; cAMP and methionine-enkephalin (met-Enk) level was determined by competitive protein binding assay and radioimmunoassay, respectively.

Results: The function of lymphocytes, obtained from BALB/c mice aged 6 and 11 months were decreased, which was restored by melatonin at the dose of 5 mg/kg or 30 mg/kg. In vitro, proliferation of lymphocytes in 11-month-old mice was decreased and cAMP level was increased. Melatonin (0.1 nmol/L or 1 micromol/L) had negative regulation to this. Forskolin (10 micromol/L) enhanced the cAMP level of lymphocytes in 2- and 11-month-old mice (P<0.01), which was antagonized partially by melatonin and this effect of melatonin was also abolished by pertussis toxin (1 mg/L) completely. Melatonin (1 micromol/L and 0.1 nmol/L) increased the content of met-Enk of lymphocytes in 2- and 11-month-old mice, respectively (P<0.01), which was blocked by nifedipine (1 micromol/L).

Conclusion: Melatonin exerted an effect on immune responses in mice of different months, which might be mediated by G protein-AC-cAMP signal transduction pathway and regulation of met-Enk level.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Age Factors
  • Animals
  • Cell Division / drug effects
  • Cell Separation
  • Cyclic AMP / biosynthesis
  • Enkephalin, Methionine / metabolism*
  • GTP-Binding Proteins / metabolism
  • Immunity / drug effects*
  • Immunity / immunology
  • Interleukin-2 / biosynthesis
  • Lymphocytes / drug effects*
  • Lymphocytes / immunology
  • Melatonin / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Rats
  • Signal Transduction

Substances

  • Adjuvants, Immunologic
  • Interleukin-2
  • Enkephalin, Methionine
  • Cyclic AMP
  • GTP-Binding Proteins
  • Melatonin