fig1

Figure 1. Inflammatory signaling inhibited by colchicine, canakinumab and methotrexate. The NLRP3 inflammasome is inhibited upstream to its assembly by colchicine, whereas canakinumab acts downstream, after caspase-1-dependent cleavage of pro-IL-1β. Methotrexate has multiple effects including inhibition of AICAR transformylase, leading to AICAR accumulation and adenosine release at inflamed sites. AICAR: 5-aminoimidazole-4-carboxamide ribonucleotide; CRP: C reactive protein; IL: interleukin; NET: neutrophil extracellular traps; NLRP3: nucleotide-binding oligomerization domain(NOD)-like receptor (NLR) family pyrin domain containing protein 3 (NLRP3); PAI-1: plasminogen activator inhibitor type 1.