261 Colchicine Attenuates Inflammation Beyond the Inflammasome of the NLRP3 inflammasome inhibition, as suggested by a 10.7% reduction of NF-κB (nuclear factor–κB) essential modulator (PFDR=0.008), an activator of NF- κB, which is necessary for NLRP3 inflammasome activation. Eleven proteins showed a large median reduction (>10%) after colchicine (Figure). These proteins are not directly involved in the NLRP3 inflammasome pathway; glycoprotein VI (−15.3%; PFDR<0.001), CD40 ligand (−15.2%; PFDR<0.001), pro–IL-16 (−13.7%; PFDR=0.002), and C-C motif chemokine 17 (−10.0%; PFDR=0.007) play important roles in the adaptive immune system, hemostasis, or both. The strongest attenuation was observed in proteins involving neutrophil degranulation: myeloblastin (−25.7%; PFDR<0.001), carcinoembryonic antigenrelated cell adhesion molecule 8 (−25.4%; PFDR<0.001), azurocidin (−20.4%; PFDR<0.001), and myeloperoxidase (−15.2%; PFDR<0.001) showed strong reductions after colchicine, and all are present in the granules of neutrophils. Neutrophils are the main source of circulating urokinase plasminogen activator surface receptor (−10.1%; PFDR<0.001). Colchicine accumulates preferably in neutrophils, interfering with neutrophil adhesion, mobilization, and recruitment, and inhibiting neutrophil chemotaxis and superoxide production.3 Our results support an important inhibitory effect of colchicine on neutrophils, which have been suggested to contribute to progression of atherogenesis.4 Twenty-three proteins showed significant median increase after colchicine treatment (PFDR<0.05). The strongest increase was measured in levels of intestinal fatty acid–binding protein (18.5%; PFDR=0.027), a biomarker of intestinal barrier dysfunction, and myoglobin (17.8%; PFDR<0.001), the oxygen-carrying pigment of muscle tissues related to myopathy, which might relate to the occurrence of known (subclinical) gastrointestinal and myopathic side effects of colchicine.5 Protein-glutamine γ-glutamyltransferase 2 (15.2%; PFDR<0.001) is related to tissue repair, whereas fibroblast growth factor 21 (11.8%; PFDR<0.001) and insulin-like growth factor-binding protein 1 (10.6%; PFDR<0.001) could protect against atherosclerosis (Figure). Treatment with colchicine resulted in a significant reduction of median highsensitivity C-reactive protein from 1.52 mg/L (interquartile range, 0.66–3.43 mg/L) to 1.00 mg/L (interquartile range, 0.37–2.28 mg/L; PFDR<0.001). In only 6 proteins, change in high-sensitivity C-reactive protein correlated significantly with change in protein level: IL-6 (r=0.461; PFDR<0.001), E-selectin (r=0.273; PFDR=0.008), matrix metalloproteinase-9 (r=0.241; PFDR= 0.028), cathepsin Z (r=0.240; PFDR=0.022), retinoic acid receptor responder protein 2 (r=0.232;
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