CASP4 and Sepsis: Given that expression of caspase-4 and -5 is also increased during IBD it is worth questioning whether a portion of HMGB1 secretion can be attributed to non-canonical inflammasome signalling and that HMGB1-LPS internalisation may contribute to the sustained inflammation of the mucosa via activation of caspase-4 or -5, as is the case in sepsis (Williams et al., 2015b; Flood et al., 2015; Kayagaki et al., 2021).