Negative regulators such as GTP-binding protein or CARD8 have been strongly associated with a protective function in CD through inhibition of the inflammasome NLRP3 complex assembly (47), meanwhile other factors such as oxidative species and LPS act as a strong signal to induce NF-кB activation, which, in turn, activate IL-1β and IL-18 and their release into the inflamed colon. This evidence concerns the gene IL18 and Cowden disease.