| First Author | Hunger RE | Year | 1997 |
| Journal | Eur J Immunol | Volume | 27 |
| Issue | 1 | Pages | 255-61 |
| PubMed ID | 9022027 | Mgi Jnum | J:37643 |
| Mgi Id | MGI:85034 | Doi | 10.1002/eji.1830270138 |
| Citation | Hunger RE, et al. (1997) Prevention of autoimmune diabetes mellitus in NOD mice by transgenic expression of soluble tumor necrosis factor receptor p55. Eur J Immunol 27(1):255-61 |
| abstractText | The non-obese diabetic (NOD) mouse represents a relevant animal model of autoimmunity for insulin-dependent diabetes mellitus. The pathogenic role of tumor necrosis factor (TNF) in insulitis and beta cell destruction observed in these mice remains controversial, since injections of TNF or of anti-TNF antibodies have been reported to exert protection or acceleration of diabetes, depending on the timing of administration. In this study, we demonstrate that, in contrast to the non-transgenic littermates, NOD mice with permanent neutralization of TNF by high blood levels of soluble TNF receptor p55-human FcIgG3-fusion molecules resulting from the expression of a transgene are protected from spontaneous diabetes. They are also protected from accelerated forms of disease caused by transfer of NOD spleen cells or cyclophosphamide injections. This protection is associated with a marked decrease in the severity and incidence of insulitis and in the expression of the adhesion molecules MAdCAM-1 and ICAM-1 on the venules of pancreatic islets. These data suggest a central role for TNF-alpha in the mediation of insulitis and of the subsequent destruction of insulin-secreting beta-cells observed in NOD mice. They may be relevant to cell-mediated autoimmune diseases in general, in which treatment with soluble TNF receptors might be beneficial. |
