| Type 1 diabetes mellitus (T1DM) is an autoimmune disease resulting from progressive specific destruction of the insulin-producingβ-cells in the pancreatic islets by the immune system. T1DM is a disease of multifactorial inheritance, many complicated interacted factors and immune cells, such as T cells, B cells, macrophages and dendritic cells, contribute to its pathogenesis. Accumulated evidence has suggested that the switch of the immune balance between Th1 and Th2 lymphocytes towards Th1-dominated response is the main cause of this autoimmune disease.Chitosan is a cationic biocompatible polysaccharide composed of repeated units of N-acetyl-D-glucosamine and D-glucosamine, derived from the non-acetylated or partial deacetylation of chitin. It has been well known for its biological activities such as its antibacterial, cholesterol-lowering, antitumor, antidiabetic and immunomodulatory effects. In vivo studies have shown that chitosan can be used as an antidiabetic agent, because it can improve the metabolism, promote insulin-sensitizing and antihyperglycemic activity of diabetic rats. In addition, in vitro studies also confirm the positive effect on the function and proliferation of pancreasticβcells. But, according to our knowledge, currently there is no data on immunotherapeutic effects of chitosan on T1DM. So, in our study we investigate the immunotherapeutic effects of WSC on Multiple low dose-STZ (MLD-STZ) induced T1DM in mice and elucidate the possible molecular and immune mechanism underling WSC's immunotherapeutic profiles on T1DM.T1DM mice model was successfully established by MLD-STZ, the characteristics of expression of related cytokines, and the pathology of mouse pancreas were analyzed on day 7 and day 14 after the first injection of STZ. MLD-STZ treatment mice developed hyperglycaemia within 2 weeks after the first STZ injection. Histochemistry analysis showed that on day 14 there was extensive lymphocytic infiltration, destruction on normal islet architecture.And MLD-STZ significantly increased Th1 cytokine (IFN-γand TNF-α) mRNA expression in both pancreas and spleens on day 7 and day 14. Th2 cytokine IL-4 was significantly downregulated in pancreas on day 14. IFN-γ/IL-4 ratio on day 7 and day 14 was also caculated, and this ratio was significantly different from normal control mice. Serum production of IFN-γand IFN-γ/IL-4 ratio was sharply upregulated on day 7 and day 14.To access the immunotherapeutic effect of WSC in T1DM mice, T1DM mice were randomly divided into two groups: diabetic control group and diabetic group drinking 0.6% WSC, and normal mice not treated with STZ were offered into normal control group. After 12 weeks'WSC treatment, the non-fasting blood glucose level was significantly lowered in WSC treated mice. Histological analysis of pancreas showed that WSC treatment significantly attenuates insulitis development, but not completely. Immunohistochemistry study also indicated WSC treated group pancreas islets possessed more insulin-positiveβcells. Analysis of relative cytokines levels by Real-time RT-PCR and ELISA showed that WSC treatment significantly lowered related Th1 cytokines levels,up-regulated some Th2 cytokines expressions and lowered IFN-γ/IL-4 ratio in T1DM mice. These result showed that the imbalance of Th1 and Th2 in T1DM mice was successfully rescued.These data showed that WSC treatment has prominent immunotherapeutic effect in T1DM mice, and this immunotherapeutic effect may be attributed to the successful recovery of the imbalance of Th1 and Th2 in T1DM mice.
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