Immunomodulation therapy of diabetes by oral administration of a surfactin lipopeptide in NOD mice

Type 1 diabetes mellitus (T1DM) is considered an autoimmune disease, which can be attenuated by modulation of immune pathway from Th1- to Th2-type through vaccination. WH1fungin surfactin is a Bacillus-produced natural immunomodulator. NOD mice were orally treated with 5 mg/kg or 25 mg/kg WH1fungin once a week for total 4 weeks. After the final administration, the diabetes incidence and the anti-inflammatory roles of WH1fungin were investigated by immunohistochemistry, FACS and ELISA. The results showed oral WH1fungin obviously resulted in a WH1fungin-unspecific suppression of T1DM. Diabetes incidence was significantly reduced when compared to phosphate buffered saline (PBS) control. Mice in the control group began to be onset of diabetes at week 15, following with an increased mortality from week 16 to 28. At the end of observation, the diabetes incidence reached to 81% at week 30, while only 25% in WH1fungin groups. The splenocytes assay showed oral WH1fungin could suppress T cells proliferation, down-regulate amounts of activated CD8+ T cells with the production of tumor necrosis factor (TNF)-α and interferon (IFN)-γ, and increase CD4+CD25+FOXP3+ regulator T cells (Tregs). The serum assay revealed oral WH1fungin down-regulated TNF-α and IgG2a but increased interleukin (IL)-10 and IgG1 in mice. All of these data showed oral WH1fungin tended to switch the immune response from Th1- to Th2-type. The further surveys revealed that less IFN-γ but more transfer growth factor (TGF)-β were found in the islets of mice with oral WH1fungin when compared to that in the control group. As a result, the normal islet architecture and slight inflammatory cells infiltration was observed with a slight insulitis in the oral WH1fungin groups. These results demonstrate that oral WH1fungin might be a novel therapeutic approach for the prevention of T1DM.