title: Prevention of autoimmune diabetes and induction of β-cell proliferation in NOD mice by hyperbaric oxygen therapy.
abstract: We evaluated the effects of hyperbaric oxygen therapy (HOT) on autoimmune diabetes development in nonobese diabetic (NOD) mice. Animals received no treatment or daily 60-min HOT 100% oxygen (HOT-100%) at 2.0 atmospheres absolute and were monitored for diabetes onset, insulitis, infiltrating cells, immune cell function, and β-cell apoptosis and proliferation. Cyclophosphamide-induced diabetes onset was reduced from 85.3% in controls to 48% after HOT-100% (P < 0.005) and paralleled by lower insulitis. Spontaneous diabetes incidence reduced from 85% in controls to 65% in HOT-100% (P = 0.01). Prediabetic mice receiving HOT-100% showed lower insulitis scores, reduced T-cell proliferation upon stimulation in vitro (P < 0.03), increased CD62L expression in T cells (P < 0.04), reduced costimulation markers (CD40, DC80, and CD86), and reduced major histocompatibility complex class II expression in dendritic cells (DCs) (P < 0.025), compared with controls. After autoimmunity was established, HOT was less effective. HOT-100% yielded reduced apoptosis (transferase-mediated dUTP nick-end labeling-positive insulin-positive cells; P < 0.01) and increased proliferation (bromodeoxyuridine incorporation; P < 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.
authors.affiliation: Diabetes Research Institute, Cell Transplant Center, University ofMiami, Miami, Florida, USA.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Faleo
authors.forename: Carmen
authors.initials: C
authors.lastname: Fotino
authors.forename: Nicola
authors.initials: N
authors.lastname: Bocca
authors.forename: R Damaris
authors.initials: RD
authors.lastname: Molano
authors.forename: Elsie
authors.initials: E
authors.lastname: Zahr-Akrawi
authors.forename: Judith
authors.initials: J
authors.lastname: Molina
authors.forename: Susana
authors.initials: S
authors.lastname: Villate
authors.forename: Oliver
authors.initials: O
authors.lastname: Umland
authors.forename: Jay S
authors.initials: JS
authors.lastname: Skyler
authors.forename: Allison L
authors.initials: AL
authors.lastname: Bayer
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
authors.forename: Antonello
authors.initials: A
authors.lastname: Pileggi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000276:immunology; D019013:CD40 Antigens / Q000096:biosynthesis / Q000276:immunology; D049109:Cell Proliferation; D003520:Cyclophosphamide / Q000009:adverse effects; D003713:Dendritic Cells / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005802:Genes, MHC Class II / Q000276:immunology; D006931:Hyperbaric Oxygenation; D007166:Immunosuppressive Agents / Q000009:adverse effects; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D019041:L-Selectin / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D010195:Pancreatitis / Q000276:immunology / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D007166:Immunosuppressive Agents; D019041:L-Selectin; D003520:Cyclophosphamide