Protection from autoimmune diabetes by adjuvant therapy in the non-obese diabetic mouse: the role of interleukin-4 and interleukin-10.
Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that is characterized by the destruction of insulin-producing beta-cells in the pancreatic islets. A single administration of CFA prevents clinical hyperglycaemia in non-obese diabetic (NOD) mice. We have previously shown that CFA administration does not eliminate insulitis in the pancreas of the treated animals, but diverts the disease process from a destructive to a non-destructive pathway. We provide evidence that this phenomenon may be under cytokine control. Neutralizing monoclonal antibodies against IL-4 and IL-10 were injected, singularly or in combination, into CFA-treated NOD mice. Antibody treatment did not lead to the development of overt diabetes; however, a marked impairment of glucose tolerance was shown in about one half of the mice treated with a combination of the two antibodies at the end of the study. This functional abnormality correlated with the histological loss of pancreatic islet tissue. These studies suggest a role for IL-4 and IL-10 in CFA-induced protection from diabetes in the NOD mouse. They also suggest that, in this animal model, the nature of the autoimmune response to islet tissue (either destructive or non-destructive) may reflect the relative proportion of Th1- and Th2-type cytokines produced in the lesions.
Calcinaro
F
F
Barbara Davis Center for Childhood Diabetes, University of Colorado, Health Sciences Center, Denver, USA.
Gambelunghe
G
G
Lafferty
K J
KJ
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000517:prevention & control*; D005260:Female; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D016753:Interleukin-10; D015847:Interleukin-4