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.