Oral Use of Interferon-alpha Delays the Onset of Insulin-Dependent Diabetes Mellitus in Nonobese Diabetes Mice

Abstract

Insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetes (NOD) mouse model is thought to be an autoimmune CD4 Th1-like cell-mediated disease. We tested the efficacy of oral use of interferon-alpha (IFN-alpha) therapy on IDDM in NOD mice. Using urine and blood sugar levels as indicators of IDDM, oral administration of murine IFN-alpha (100 IU/body) to NOD mice significantly delayed the onset of symptomatic diabetes. However, oral use of IFN-alpha did not prevent diabetic NOD mice from losing weight once NOD mice were symptomatic, suggesting that orally administered IFN-alpha is a prophylactic rather than therapeutic approach to the management of IDDM.

Interferon-α initiates type 1 diabetes in nonobese diabetic mice

“…Previous studies have shown that oral IFN-␣ treatment of NOD mice 5 week or older significantly suppressed the development of insulitis and diabetes (15,16). By 5 weeks of age, however, the principal autoimmune responses have already been established in the PLNs (1).…”

“…Additionally, IFN regulatory factor 1-deficient NOD mice failed to develop insulitis and diabetes (14). However, some studies have shown that oral treatment of prediabetic NOD mice with IFN-␣ suppressed insulitis and diabetes (15,16). Thus, the role that IFN-␣ plays in the pathogenesis of T1D in NOD mice is controversial.…”

Central role of defective apoptosis in autoimmunity

“…The NOD mouse thus represents a newly defined mosaic model of discordant MHC gene expression that exhibits marked proteasome dysfunction in an age-and tissue-specific manner. The delayed maturation of lymphocytes and cytokine abnormalities apparent in NOD mice that spontaneously develop type I diabetes are mirrored, in part, by the clinical phenotypes of knockout mice lacking NF-B subunits or LMP2 (Van Kaer et al 1994, Sha et al 1995, Beg & Baltimore 1996, Snapper et al 1996, Franzoso et al 1997, Horwitz et al 1997, Iotsova et al 1997, Caamano et al 1998, Tanaka et al 1999. The clinical relevance of the phenotypes of the NOD mouse and of these various knockout animals to human disease is supported by the existence of nearly identical cytokine and lymphocyte maturation defects in humans with type I diabetes (Van Kaer et al 1994, Sha et al 1995, Beg & Baltimore 1996, Snapper et al 1996, Franzoso et al 1997, Horwitz et al 1997, Iotsova et al 1997, Caamano et al 1998, Tanaka et al 1999 (Fig.…”

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].…”