Induction of type I diabetes by interferon-alpha in transgenic mice.
Type I diabetes is an autoimmune disease involving an interaction between an epigenetic event (possibly a viral infection), the pancreatic beta cells, and the immune system in a genetically susceptible host. The possibility that the type I interferons could mediate this interaction was tested with transgenic mice in which the insulin-producing beta cells expressed an interferon-alpha. These mice developed a hypoinsulinemic diabetes associated with a mixed inflammation centered on the islets. The inflammation and the diabetes were prevented with a neutralizing antibody to the interferon-alpha. Thus, the expression of interferon-alpha by the beta cells could be causal in the development of type I diabetes, which suggests a therapeutic approach to this disease.
Stewart
T A
TA
Department of Endocrine Research, Genentech, Inc., South San Francisco, CA 94080.
Hultgren
B
B
Huang
X
X
Pitts-Meek
S
S
Hully
J
J
MacLachlan
N J
NJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D005260:Female; D005934:Glucagon / Q000032:analysis; D007328:Insulin / Q000032:analysis / Q000097:blood; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007963:Leukocytes, Mononuclear; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009500:Neutralization Tests; D013004:Somatostatin / Q000032:analysis
D000911:Antibodies, Monoclonal; D007328:Insulin; D016898:Interferon-alpha; D013004:Somatostatin; D005934:Glucagon