There are multiple pathways of pro-IL-1β processing and production of active protein involved in CMO development in mice, including NLRP3 inflammasome/caspase-1, additional mechanism involving caspase-8, and neutrophil proteases (multiple have been tested in Pstpip2cmo mice, including elastase, proteinase 3, cathepsins B, C, G) (7, 24). This evidence concerns the gene CASP8 and chronic recurrent multifocal osteomyelitis.