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