Serum IFN-γ and IL-10 levels are associated with disease progression in non-obese diabetic mice

Background The goal of the present study was to determine whether cytokines in the peripheral blood of naive NOD mice correlate with the disease process and thereby would provide a marker for monitoring disease activity. Methods Female NOD mice (5, 10 and 14-16weeks of age) were investigated in a cross-sectional study. In the group of 14-16-week-old mice, non-diabetic and diabetic mice were analysed as different subgroups. The Th1 cytokine (IFN-gamma) and the Th2 cytokine (IL-10) were quantified in serum by sandwich enzyme-linked immunosorbent assay (ELISA). Pancreatic 2 mRNA for IFN-gamma and IL-10 was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) from the same animals. Results Serum levels of IFN-gamma were initially low but increased with age in NOD mice, reaching the highest levels at diabetes onset (p < 0.002 compared to 10 weeks). A similar rise was noted in IFN-gamma gene expression in pancreatic lesions. In contrast, an early peak of serum IL-10 levels was observed in nondiabetic NOD mice (10 weeks) at a stage where non-destructive insulitis occurs. With increasing age a continuous loss of IL-10 until progression towards diabetes was observed. The pancreatic IL-10 mRNA expression correlated with serum IL-10 changes. As a consequence, the ratio of IFN-gamma IL-10, reflecting the Th1/Th2 balance in the serum, was significantly increased in diabetic compared to non-diabetic NOD mice (p < 0.005). Conclusion These results demonstrate, for the first time, that an increased Th2 pattern in the non-diabetic stage preceding a Thl shift is associated with the development of diabetes in naive NOD mice. Serum cytokines correlate with disease progression and pancreatic cytokine expression during prediabetes. Soluble cytokines measured in the periphery are therefore promising surrogate markers of diabetes development. Copyright (C) 2002 John Wiley Sons, Ltd.