Effect of Interferons and Poly(I):Poly(C) on the Pathogenesis of the Diabetogenic Variant of Encephalomyocarditis Virus in Different Mouse Strains

Abstract

Interferon (IFN) can either prevent or exacerbate the pathogenic effects of the diabetogenic variant of encephalomyocarditis (EMC-D) virus. The effect seen is dependent upon the mouse strain and the time of IFN administration. For example, IFN-alpha beta protects SWR/J but not ICR Swiss male mice against the diabetogenic effects of the virus. Administration of either IFN-alpha beta or the IFN-inducer poly(I):poly(C) 4 days post infection, results in an exacerbation of the infection in ICR Swiss and C57BL/6 male mice. Studies have been initiated to investigate the role of the IFN system in the pathogenesis of this virus infection. In this study IFNs or poly(I):poly(C) were administered to several mouse strains at 24 h before or 4 days after infection with EMC-D virus. The results of such treatment ranged from complete protection of the animals from the diabetogenic effects of the virus to exacerbation of the infection as reflected by the virus content in selected organs. The effect was dependent upon the mouse strain, the type of IFN, and the time of its administration in relation to virus infection.

Interferons as pathogenic effectors in autoimmunity

“…Moreover, a monoclonal antibody to the specific IFN‐α transgene product could block the disease process, indicating that the pathogenic manifestations were a consequence of the IFN‐α production rather than some other effects of the transgene. Strong induction of IFN‐α/β by high doses of poly I:C (5 µg/g body weight) was also shown to enhance development of diabetes in BioBreeding (BB) rats (117, 118) and in mice treated with streptozotocin (118) or encephalomyocarditis virus (119) or expressing a transgenic B7‐1 (CD80) costimulatory molecule in β cells (120).…”

D Variant of Encephalomyocarditis Virus (EMCV-D)-Induced Diabetes Following Natural Killer Cell Depletion in Diabetes-Resistant Male C57BL/6J Mice

“…When susceptible strains of mice (ICR Swiss, BALB/cBy, DBA/2, SWR and others) are infected with the D variant of EMCV, pancreatic beta islets are destroyed and a syndrome similar to human insulin-dependent diabetes results (1,2,3). The virus also replicates in several other organs including the brain, heart and spleen (3,9).…”

GM-CSF-induced autoimmune gastritis in interferon α receptor deficient mice

“…Whereas type 1 IFNs have been implicated in certain autoimmune disease development in man and mice [23,24,28,[42][43][44][45][46][47][48][49][50][51][52][53][54][55], in other instances they have been reported to ameliorate disease [26,[56][57][58][59][60][61]. In SLE patients, serum IFN-a increased during flares and was associated with multiple organ involvement [62][63][64][65].…”