Effects On Inhibition Of Interleukin-17F In Mice With Experimental Ulcerative Colitis

Ulcerative colitis(UC) belongs to a type of inflammatory bowel disease(IBD) that is a chronic, often relapsing, nonspecific inflammatory bowel disease, and its etiology and pathogenesis is still not very clear. Now, we considered that the interaction of multiple factors lead to the occurrence of UC. The closely related factors include the intestinal immune dysfunction, individual genetic susceptibility, intestinal flora imbalance and environmental factors and so on. In particular, the immune function abnormality plays an important role in the development of UC. In recent years, foreign study found a new T cell subsets——T helper 17 cells(Th17) that to maintain the function of mucosal barrier is significant. In addition, interleukin-17F(IL-17F) as the main cytokine of Th17 cells that is a kind of inflammation medium involved in inflammation even to cause a variety of autoimmune diseases, including UC. Therefore, we use IL-17 F antibody(IL-17 F Ab) specific block the IL-17 F to inhibit the immune effect of Th17 cell.Then the inhibition of IL-17 F will influence the occurrence of UC and induce the remission of disease that provide a new study for the clinical treatment of UC.In order to study the inhibition of IL-17 F in mice with experimental ulcerative colitis, 24 female C57BL/6J mice were randomly divided into 3 groups.The three groups consist of DSS+IL-17 F Ab group, DSS+PBS group and Normal+PBS group. DSS+IL-17 F Ab group and DSS+PBS group were treated with 5% dextran sulfate sodium(DSS) solution as the only drinking water let the animal free drinking; Normal+PBS group with distilled water as the only drinking water let the animal free drinking. On fourth day, seventh day and tenth day after treatment with DSS, the DSS+IL-17 F Ab group was conducted intraperitoneal injection of IL-17 F Ab 100ug; PBS solution to DSS+PBS group and Normal+PBS group with the same dose. Then, we observed the daily changes of body weight, stool, fecal occult blood condition of the mice. The mice were sacrificed according to the ethical requirements after the fourteenth day. The general morphology and histopathological changes of colon tissue were observed while histological score of inflammatory damage assessment were executed.In the last, we collected the venous blood for serum extraction to complete the ELISA detection.The experimental results show that the DSS+PBS group and DSS+IL-17 F Ab group compared to Normal+PBS group, through IL-17 F Ab to block the IL-17 F specifically, daily disease activity index(DAI) were significantly increased(P<0.001). And from the experiment began to the eighth day, the DSS+IL-17 F Ab group compared with DSS+PBS group had no significant differences about the DAI score; from the ninth day to 14 th day, the former showed a declining trend(P<0.05). The colon length of DSS+PBS group and DSS+IL-17 F Ab group was(5.855±0.114) cm、(7.300±0.173) cm respectively. Furthermore, the DSS+PBS group was more significantly shortened(P<0.01). The inflammatory damage assessment data indicated that the histological scores of DSS+PBS group manifestations and pathological features is largely analog of UC patients. By using IL-17 F Ab specific block the IL-17 F show that DSS+IL-17 F Ab group compared with DSS+PBS group had a good therapeutic effect on both the DAI score and the degree of inflammatory injury. The inhibition of IL-17 F achieved the treatment goals about alleviated the clinical symptoms and mucosal healing were induced. Moreover, through ELISA detected that the relationship between the change of IL-17 F expression and the outcome of mice with experimental UC provides a strong evidence for the view of“To block the IL-17 F can significantly relieve the occurrence and development of UC”.Therefore, IL-17 F is expected to become a new strategy of UC therapeutic target that lining for the clinical treatment of UC.