Ingested interferon alpha suppresses type I diabetes in non-obese diabetic mice

• Published in: Diabetologia 1998-10, Vol.41 (10), p.1227-1232
• Main Authors: Brod, S A, Malone, M, Darcan, S, Papolla, M, Nelson, L
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Concanavalin A - pharmacology; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - prevention & control; Female; Interferon-alpha - administration & dosage; Interferon-alpha - therapeutic use; Interferon-gamma - metabolism; Interleukin-10 - biosynthesis; Interleukin-4 - biosynthesis; Interleukins - biosynthesis; Ionomycin - pharmacology; Mice; Mice, Inbred NOD; Myristic Acid - pharmacology; Palmitic Acid - pharmacology; Spleen - immunology; Tetradecanoylphorbol Acetate - pharmacology; Transforming Growth Factor beta - metabolism
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s001250051056

Type I diabetes mellitus is a chronic disorder that results from autoimmune destruction of the insulin-producing pancreatic beta cell. The non-obese diabetic mouse is a model of the human autoimmune disease Type I diabetes [1-3]. We have previously shown that ingested type 1 interferon inhibits chronic relapsing experimental autoimmune encephalomyelitis and the adoptive transfer of experimental autoimmune encephalomyelites by T cells, and decreases both antigen-specific and mitogen-induced pro-inflammatory cytokine secretion in this disorder. We therefore tried to determine whether ingested murine interferon alpha inhibits insulinitis and suppresses Type I diabetes mellitus in non-obese diabetic mice. Murine interferon alpha, given daily, decreased islet inflammation and suppressed diabetes. It increased the concanavalin A and ionomycin plus myristic acid palmitic ester-induced production of interleukin 4 and 10 and interferon gamma-secretion in spleen cells from treated mice. Adoptive transfer of unstimulated splenocytes secreting interleukin 4 and interleukin 10 from fed interferon alpha donors suppressed spontaneous diabetes mellitus in recipients. The protective effect of adoptively transferred unstimulated splenocytes shows the presence of ingested interferon alpha-activated regulatory splenic cell populations that may work via increased interleukin 4 or interleukin 10 production. Ingested interferon alpha administered during vulnerable periods in at-risk populations may potentially provide a continuous, convenient, non-toxic and effective treatment for Type I diabetes.