Differential Regulation of Th1-Type and Th2-Type Cytokine Profiles in Pancreatic Islets of C57BL/6 and BALB/c Mice by Multiple Low Doses of Streptozotocin

In the nonobese diabetic (NOD) mouse, the T helper (Th)1-type inflammatory cytokines interferon (IFN)-g and tumor necrosis factor (TNF)-a play a critical role in the development of type 1 diabetes, whereas the Th2-type anti-inflammatory cytokines interleukin (IL)-4 and IL-10 operate counterregulatory. There are no comprehensive analyses on cytokine profiles in the mouse model of diabetes induced with multiple low doses of streptozotocin (MLD-STZ). Therefore, we used islets to study ex vivo effects of MLD-STZ and in vitro effects of STZ on IFN-g, TNF-a, IL-4, and IL-10 on both levels of protein-producing cells and the mRNA expression, as well as the mRNA expression of the Th3-type cytokine transforming growth factor TGF-b1. C57BL/6 and BALB/c mice of both genders were injected intraperitoneally with 40 mg/kg body wt STZ on five consecutive days and islets were isolated on day 1 and 3 after the fifth STZ-injection. Control mice received the solvent of STZ. In islets of C57BL/6 mice of both genders MLD-STZ similarly stimulated production of IFN-g and TNF-a, but significantly reduced IL-4 and IL-10 levels in male mice only. Opposite results were obtained in islets of BALB/c mice of both genders. Here, MLD-STZ markedly decreased the levels of IFN-g and TNF-a, but significantly increased the levels of IL-4 and IL-10. The functional results were in line with MLD-STZ effects on the mRNA expression of the cytokines.