Fever-range whole body hyperthermia prevents the onset of type 1 diabetes in non-obese diabetic mice

Abstract

PURPOSE: Type 1 diabetes (T1D) is an autoimmune disease in which the insulin producing beta cells of the pancreatic islets are destroyed by cytotoxic T lymphocytes (CTLs). It has been demonstrated that the injection of complete Freund's adjuvant (CFA) can prevent disease onset in non-obese diabetic (NOD) mice. This effect has been attributed to CFA-enhanced natural killer (NK) cell mediated control of autoimmune CTLs. Fever-range whole body hyperthermia (FR-WBH) has also been shown to stimulate NK cell cytotoxicity. This led to the hypothesis that FR-WBH can prevent disease onset in NOD mice by a thermally regulated mechanism. METHODS: FR-WBH or mock treatment was administered weekly until the NOD mice reached 32 weeks of age. Blood glucose levels were monitored weekly, with measurements > or =33.5 mM indicating onset of diabetes, at which time the mice were euthanized for histological and cellular analyses. RESULTS: Weekly FR-WBH prevented the onset of T1D in NOD mice and this effect correlated with increased NK cell cytotoxicity and control of blood glucose concentration. Histological analysis revealed significantly fewer lymphocytes infiltrating the pancreatic islets of FR-WBH treated mice than those of untreated mice, suggesting a relationship between thermally induced protection of beta cells and their ability to regulate blood glucose concentrations. CONCLUSIONS: These studies show, for the first time, that mild systemic hyperthermia can prevent the generation of T1D in a clinically relevant mouse model. Further study of the thermally sensitive aspects of immunoregulation could lead to the development of heat-based therapies for the prevention or treatment of autoimmune diseases.