We evaluated the effects of hyperbaric oxygen therapy (HOT) on autoimmune diabetes development in nonobese diabetic (NOD) mice. Spontaneous diabetes incidence reduced from 85% in controls to 65% in HOT-100% (= 0.01). Prediabetic mice receiving HOT-100% showed lower insulitis scores reduced T-cell proliferation upon Bepotastine stimulation in vitro (< 0.03) increased CD62L expression in T cells (< 0.04) reduced costimulation markers (CD40 DC80 and CD86) and reduced major histocompatibility complex class II expression in dendritic cells (DCs) (< 0.025) compared with controls. After autoimmunity was established HOT was less effective. HOT-100% yielded reduced apoptosis (transferase-mediated dUTP nick-end Bepotastine labeling-positive insulin-positive cells; < 0.01) and increased proliferation (bromodeoxyuridine incorporation; < 0.001) of insulin-positive cells compared with controls. HOT reduces autoimmune diabetes incidence in NOD mice via increased resting T cells and reduced activation of DCs with preservation of β-cell mass resulting from decreased apoptosis and increased proliferation. The safety profile and noninvasiveness makes HOT an appealing adjuvant therapy for diabetes prevention and intervention trials. Type 1 diabetes (T1D) is a chronic autoimmune disorder caused by autoreactive T cells which mediate the destruction of insulin-producing pancreatic β-cells leading to lifelong dependence on exogenous insulin. Methods to achieve and maintain normoglycemia are currently based on insulin therapy diet and Bepotastine exercise. Unfortunately while able to delay/prevent chronic complications of diabetes intensive insulin therapy does not always achieve tight daily glycemic control and is associated with increased frequency of severe hypoglycemia. An Rabbit Polyclonal to PEBP1. ideal treatment for T1D may combine strategies aimed at restoring self immune tolerance with others focused on preservation/restoration of functional β-cell mass. Different approaches have been proposed (1) including prevention studies in high-risk subjects timely interventions at the time of diabetes onset delayed interventions to restore self-tolerance and β-cell regeneration and replacement of β-cell mass via islet or pancreas transplantation (2). Desirable therapeutic regimens should be effective (alone or in combination) readily accessible and void of severe risks for the patients (1). Multiple beneficial effects have been recognized for hyperbaric oxygen therapy (HOT) which is clinically used to improve oxygen supply to hypoperfused tissues (i.e. carbon Bepotastine monoxide exposure embolism and ischemic events and diabetic Bepotastine ulcers among other). Anti-inflammatory properties (3-7) and mobilization of bone marrow stem cells (BMSCs) that are involved in tissue repair processes (8-11) have been attributed to HOT. The known safety profile and noninvasive nature of HOT with virtually absent side effects makes its use attractive for the treatment of autoimmune diseases (12 13 In a murine lupus model HOT was associated with reduced mortality reduced proteinuria modified lymphocyte subset redistribution decreased anti-DNA antibody titers and amelioration of immune-complex deposition (14). The non-obese diabetic (NOD) mouse can be widely used like a preclinical style of T1D to assess restorative approaches in a position to prevent/halt autoimmune-mediated β-cell loss although the success in diabetes prevention has been difficult to translate to the clinical arena (15-17). Herein we report that HOT can prevent/delay the onset of autoimmune Bepotastine diabetes in NOD mice and that this phenomenon is associated with increased β-cell proliferation. RESEARCH DESIGN AND METHODS Animals. Studies were approved by the institutional animal care and use committee. NOD/MrkTac mice (Taconic) NOD.CB17-test two-group comparison and one-way ANOVA for multiple comparisons were used. All in vitro determinations are means ± SEM from at least three independent conditions. Results were considered statistically significant at < 0.05. RESULTS Prevention of accelerated autoimmune diabetes onset in NOD mice by chronic HOT. CyP administration leads to accelerated diabetes onset in NOD mice (23-25). A.