NLRP3 Inflammasome Inhibitor OLT1177 Suppresses Onset of Inflammation in Mice with Dextran Sulfate Sodium-Induced Colitis.

BACKGROUND AND AIMS: NLRP3 inflammasomes have been reported to have a key role in the initiation and perpetuation of inflammatory bowel diseases (IBD). Here we investigated the effects of OLT1177, a selective inhibitor of NLRP3 inflammasomes, in mice with dextran sulfate sodium (DSS)-induced colitis. METHODS: C57BL/6J mice were given drinking water containing 3% DSS for 5 days. OLT1177 was administered for 5 days during the induction phase (simultaneously with DSS treatment) or the recovery phase (after the DSS treatment ended). The body weight and disease activity index were monitored daily. The mice were sacrificed 10 days after the start of the experiment, and the severity of inflammation in the colon was determined based on histological and biochemical analyses. RESULTS: Administration of OLT1177 during the induction phase effectively suppressed DSS colitis in terms of weight loss, disease activity index, histological score, and expression of inflammatory cytokines compared to the DSS group. In contrast, OLT1177 administration during the recovery phase did not significantly affect the colitis disease course or the results of histological analyses. CONCLUSIONS: OLT1177 was effective in preventing the onset of DSS colitis in mice. These results could guide the use of OLT1177 as a therapy for human IBD.