Methadone ameliorates multiple-low-dose streptozotocin-induced type 1 diabetes in mice

Type I diabetes is an autoimmune disease characterized by inflammation of pancreatic islets and destruction of 11, cells by the immune system. Opioids have been shown to modulate a number Of immune functions, including T helper 1 (Th1) and T helper 2 (Th2) cytokines. The immunosuppressive effect of long-term administration of opioids has been demonstrated both in animal models and humans. The aim of this Study was to determine the effect of methadone, a It-opioid receptor agonist, on type I diabetes. Administration of multiple low doses of streptozotocin (STZ) (MLDS) (40mg/kg intraperitoneally for 5 consecutive days) to mice resulted in autoimmune diabetes. Mice were treated with methadone (10 mg/kg/day subcutaneously) for 24 days. Blood glucose, insulin and pancreatic cytokine levels were measured. Chronic methadone treatment significantly reduced hyperglycemia and incidence of diabetes, and restored pancreatic insulin secretion in the MLDS model. The protective effect of methadone can be overcome by pretreatment with naltrexone, all opioid receptor antagonist. Also, methadone treatment decreased the proinflammatory Th1 cytokines [interleukin (IL)-1 beta, tumor necrosis factor-alpha and interferon-gamma] and increased anti-inflammatory Th2 cytokines (IL-4 and IL-10). Histopathological observations indicated that STZ-mediated destruction of beta cells was attenuated by methadone treatment. It seems that methadone as an opioid agonist may have a protective effect against destruction Of I cells and insulitis in the MLDS model of type I diabetes, (C) 2008 Elsevier Inc. All rights reserved.