In conclusion, QUC inhibits both the NLRP3 and AIM2 inflammasome by preventing ASC oligomerization and may be a potential therapeutic candidate for Kawasaki disease vasculitis and other IL-1 mediated inflammatory diseases.
Both IL-1α and IL-1β have been shown to induce myocarditis and aneurysm formation in <i>Lactobacillus casei</i> cell-wall extract mouse model of KD; both being successfully improved with IL-1 blockade treatment such as anakinra.
Thus, TNF and IL-1 appear to play temporally distinct roles in KD, with TNF being active in acute cardiac inflammation and IL-1 in the subsequent development of coronary vasculitis.
Our findings provide the mechanism behind the observed efficacy of rescue therapy with IL-1 blockade in recalcitrant KD, and we identify that regulation of calcium mobilization is fundamental to the underlying immunobiology in KD.
These data provide new mechanistic insights into the contributions of S100A12 and IL-1β to disease pathogenesis, and may therefore support current IL-1-targeting studies in the treatment of patients with KD.
The results also underscore the importance of the IL-1 pathway as a mediator of inflammation in KD and suggest that IL-1 or its receptor may be reasonable targets for therapy, particularly for IVIG resistant patients.
The genotype I/II for IL1-Ra and the frequency of allele II for IL1-Ra are associated with a higher susceptibility to KD, and thus may be useful markers for predicting the development of KD.