Impact of hyperglycemia on autoimmune pancreatitis and regulatory T-cells

To evaluate the influence of hyperglycemia on the progression of autoimmune pancreatitis.

We induced hyperglycemia by repetitive intraperitoneal (ip) injection of 50 mg/kg streptozotocin in MRL/MpJ mice, which develop autoimmune pancreatitis due to a genetic predisposition. We compared the extent of inflammation (histological score, CD3⁺ lymphocytes, CD8⁺ T-cells, CD4⁺ T-cells, Foxp3⁺ T-helper cells) in the pancreas of hyperglycemic and normoglycemic mice. We also analyzed the number of leukocytes, lymphocytes, granulocytes and monocytes in the blood. In addition, we determined the percentage of CD3⁺ lymphocytes, CD8⁺ T-cells, CD4⁺ T-cells, Foxp3⁺ T-helper cells, Foxp3⁺ CD25⁺ T-helper and Foxp3^- T-helper cells in the spleen by flow cytometry.

Treatment with streptozotocin caused a strong induction of hyperglycemia and a reduction in body weight (P < 0.001). Severe hyperglycemia did not, however, lead to an aggravation, but rather to a slight attenuation of autoimmune pancreatitis. In the pancreas, both the histological score of the pancreas as well as the number of CD3⁺ lymphocytes (P < 0.053) were decreased by hyperglycemia. No major changes in the percentage of CD8⁺ T-cells, CD4⁺ T-cells, Foxp3⁺ T-helper cells were observed between hyperglycemic and normoglycemic mice. Hyperglycemia increased the numbers of leukocytes (P < 0.001), lymphocytes (P = 0.016), granulocytes and monocytes (P = 0.001) in the blood. Hyperglycemia also moderately reduced the percentage of CD3⁺ lymphocytes (P = 0.057), significantly increased the percentage of Foxp3⁺ T-helper cells (P = 0.018) and Foxp3⁺ CD25⁺ T-helper cells (P = 0.021) and reduced the percentage of Foxp3^- T-helper cells (P = 0.034) in the spleen.

Hyperglycemia does not aggravate but moderately attenuates autoimmune pancreatitis, possibly by increasing the percentage of regulatory T-cells in the spleen.