Ingested interferon alpha suppresses type I diabetes in non-obese diabetic mice.
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.
Brod
S A
SA
Department of Neurology, University of Texas-Houston 77225, USA.
Malone
M
M
Darcan
S
S
Papolla
M
M
Nelson
L
L
D019264:Adoptive Transfer; D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D015759:Ionomycin / Q000494:pharmacology; D051379:Mice; D016688:Mice, Inbred NOD; D019814:Myristic Acid / Q000494:pharmacology; D019308:Palmitic Acid / Q000494:pharmacology; D013154:Spleen / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016898:Interferon-alpha; D007378:Interleukins; D016212:Transforming Growth Factor beta; D019814:Myristic Acid; D003208:Concanavalin A; D016753:Interleukin-10; D015847:Interleukin-4; D019308:Palmitic Acid; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate