Multidose streptozotocin induction of diabetes in BALB/c mice induces a dominant oxidative macrophage and a conversion of TH1 to TH2 phenotypes during disease progression

Macrophages (Mp) are implicated in both early and late phases in type 1 diabetes development. Recent study has Suggested that a balance between reductive Mp (RMp) and oxidative Mp (OMp) is possible to regulate TH1/TH2 balance. The aim of this study is to investigate the redox status of peritoneal Mp and its cytokine profile during the development Of autoimmune diabetes induced by multiple low-dose streptozotocin in BALB/c in ice. Meanwhile, the polarization of T(H)1/T(H)2 of splenocytes or thymocytes was also examined. We found that peritoneal Mp appeared as an incomplete OMp phenotype with decreased icGSH along with disease progression. The OMp showed reduced TNF-alpha, IL-12, and NO production as well as defective phagocytosis activity compared to nondiabetic controls; however, there was no significant difference with IL-6 production. On the other hand, the levels of IFN-gamma or IL-4 of splenocytes in diabetic mice were significantly higher compared to the control mice. The ratio of IFN-gamma to IL-4 was also higher at the early stage of diabetes and then declined several weeks later after the occurrence of diabetes, suggesting a pathogenetic T(H)1 phenotype from the beginning gradually to a tendency of T(H)2 during the development of diabetes. Our results implied that likely OMp maybe relevant in the development of type 1 diabetes; however, it is not likely the only factor regulating the T(H)1(H)/T(H)2 balance in MLD-STZ-induced diabetic mice.