Mo1701 Selective Janus Kinase 1 Inhibitor Targets Monocytes and Tissue Macrophages During DSS Colitis

were determined.Results: Denosumab treatment decreased the clinical disease as assessed by hyperemia and mucosal thickness and weight lose.On day 3 after colitis induction, 66% and 16% of Desnosumab-DSS-treated mice had weight loss and mucosal thickening respectively, compared to 100% and 66% of vehicle DSS-treated mice (p<0.05).Composite macroscopic score was 41% lower in Desnosumab-DSS-treated mice than in vehicle DSStreated mice (p<0.05).All four markers including diarrhea, hyperemia, thickness and adhesion were decreased.Denosumab treatment decreased the colonic MPO activity (p<0.05).Colonic IL-1b levels decreased from 41.1±1.7 in vehicle-DSS-treated mice to 13.11±1.3pg/ mg of tissue in Denosumab-DSS-treated mice (p<0.05).Conversely, no effect was evident on colonic IL-6 levels.In control mice (without colitis) Denosumab did not affect any inflammatory marker.Conclusions: These results support the hypothesis that preventative treatment with Denosumab modulates intestinal inflammation in a murine model of colitis.This provides a rationale for considering Denosumab as a therapy in CD.