title: Melatonin prolongs islet graft survival in diabetic NOD mice.
abstract: Islet transplantation has been established as a potential therapy for type 1 diabetes. However, inflammation, allorejection, and on-going autoimmune damage contribute to early graft loss and failure of islet transplantation. Melatonin is the major secretory product of the pineal gland during the dark period of each day and displays multifunctional properties including the regulation of circadian and seasonal rhythms, antioxidation reactions and immune modulation. Based on the immunosuppressive properties of melatonin, we investigated whether melatonin treatment prolonged the survival of islet grafts in non-obese diabetic (NOD) mice. The mean islet graft survival time was 7.33 +/- 1.51 and 7.75 +/- 2.66 days in untreated controls and in the solvent-treated animals, respectively. Strikingly, the mean survival time of islet grafts in recipients treated with melatonin (200 mg/kg/bw) was 17 +/- 7.76 days. Moreover, melatonin treatment reduced the proliferation of splenocytes in NOD mice. Using a T1 and T2 double transgenic mouse model, we found that T helper 1 (Th1) cells in mice treated with melatonin were significantly decreased. The reduction of Th1 cells and T cell proliferation may result from an increase in the immunosuppressive cytokine IL-10. Our results indicate that melatonin treatment suppresses autoimmune recurrence by inhibiting the proliferation of Th1 cells in NOD mice and thus prolongs the survival of syngeneic islet grafts.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Gu-Jiun
authors.initials: GJ
authors.lastname: Lin
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Huang
authors.forename: Yuan-Wu
authors.initials: YW
authors.lastname: Chen
authors.forename: Dueng-Yuan
authors.initials: DY
authors.lastname: Hueng
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Chien
authors.forename: Wei-Tso
authors.initials: WT
authors.lastname: Chia
authors.forename: Deh-Ming
authors.initials: DM
authors.lastname: Chang
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D005434:Flow Cytometry; D006085:Graft Survival / Q000187:drug effects*; D007328:Insulin / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D016688:Mice, Inbred NOD; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D002492:Central Nervous System Depressants; D007328:Insulin; D008550:Melatonin