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synergistische therapeutische wirkung durch inhibition der Phosphodiesterase VI und des interleukin 1β converting enzyms im murinen kolitismodell

Abstract This study examined new strategies for pharmacological treatment in a mouse model of chronic inflammatory bowel disease. As clinical parameters we determined the lethality and clinical score which consisted of weight loss, presence or absence of diarrhea and blood in the faeces. Further, pathoanatomical and histological data were examined. To determine the effect of pharmacological treatment on the level of cytokines, the respective concentrations were measured in the colon. The aim of this study was to determine the effect of the ICE-inhibitor Pralnacasan and the PDE-4-inhibitor Rolipram on reducing colitis. We also assessed whether a combination of both drugs might have a synergistic effect. The results showed a clear therapeutic effect of Pralnacasan, whereas Rolipram was neither effective in the clinical outcome nor in changing cytokine levels. In contrast the combination of both drugs showed a synergistic effect which prevented both occurrence of colitis in clinical measurements and increase of cytokine levels. In summary, this study proVIdes the first eVIdence that a combination of two drugs which act on different pathways proVIde a strong synergistic effect which can completely prevent the occurrence of colitis in a mouse model