Melatonin prolongs islet graft survival in diabetic NOD mice.
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.
Lin
Gu-Jiun
GJ
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Huang
Shing-Hwa
SH
Chen
Yuan-Wu
YW
Hueng
Dueng-Yuan
DY
Chien
Ming-Wei
MW
Chia
Wei-Tso
WT
Chang
Deh-Ming
DM
Sytwu
Huey-Kang
HK
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
D001786:Blood Glucose; D002492:Central Nervous System Depressants; D007328:Insulin; D008550:Melatonin