title: Interferon-alpha as a mediator of polyinosinic:polycytidylic acid-induced type 1 diabetes.
abstract: A number of studies and clinical case reports have implicated interferon (IFN)-alpha as a potential mediator of type 1 diabetes pathogenesis. Administration of polyinosinic:polycytidylic acid (poly I:C), a mimic of viral double-stranded RNA, induces diabetes in C57BL/6 mice expressing the B7.1 costimulatory molecule in islets. We investigated the potential role of IFN-alpha in this disease model. The quantitative correlation between IFN-alpha levels and time to diabetes, diabetes prevention with anti-IFN-alpha antibody, and ability of IFN-alpha itself to induce diabetes are consistent with the hypothesis that poly I:C in this model acts by induction of IFN-alpha in a genetically susceptible host. Numerous recent studies highlight the importance of the innate immune system and toll receptors in determining adaptive immune responses, and we speculate that for type 1 diabetes, viral and other environmental factors may act through induction of IFNs.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, 4200 East 9th Ave., Box B140, University of Colorado Health Sciences Center, Denver, CO 80262, USA. edwin.liu@uchsc.edu
authors.forename: Devasenan
authors.initials: D
authors.lastname: Devendra
authors.forename: Jean
authors.initials: J
authors.lastname: Jasinski
authors.forename: Evie
authors.initials: E
authors.lastname: Melanitou
authors.forename: Maki
authors.initials: M
authors.lastname: Nakayama
authors.forename: Marcella
authors.initials: M
authors.lastname: Li
authors.forename: Brooke
authors.initials: B
authors.lastname: Hensley
authors.forename: Johanna
authors.initials: J
authors.lastname: Paronen
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Moriyama
authors.forename: Dongmei
authors.initials: D
authors.lastname: Miao
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: Edwin
authors.initials: E
authors.lastname: Liu
mesh_terms: D000375:Aging; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D015870:Gene Expression / Q000187:drug effects; D016898:Interferon-alpha / Q000502:physiology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011070:Poly I-C / Q000633:toxicity*
chemical_list: D016898:Interferon-alpha; D011070:Poly I-C