Moreover, canakinumab significantly reduced the risk of recurrent flares as compared with triamcinolone acetonide. Thus, neutralization of IL-1β provides rapid and sustained pain relief and reduced the number of recurrent flares compared with steroid use. Despite the availability of several widely used TNF-α-blocking therapies for rheumatoid arthritis and other auto-immune diseases, there is a paucity of reports that blocking TNF-α provides an effective reduction in gout severity. One explanation for the lack of clinical trials of TNF-α blockade

in gout attacks is that the efficacy of TNF-α blockade in refractory gout is less than expected. One study reports a weak Ceritinib in vivo response with rather high doses of infliximab 81. There are also few publications on MSU crystals inducing TNF-α from human and mouse cells unless co-stimulated with endotoxins. Therefore, IL-1β blockade may be used for inducing long-term

remissions in refractory patients and replace glucocorticoids. If IL-1β blockade Z-VAD-FMK mouse becomes the standard of care in refractory gout, it would be consistent with the unique role of IL-1β in the pathogenesis of auto-inflammatory diseases. The evidence that IL-1β was toxic for the insulin-producing β-cell begins in 1985 using anti-human IL-1β immunoaffinity chromatography 82. This was a milestone report that advanced the field of “soluble factors” from mononuclear phagocytes playing a pivotal role in the pathogenesis of diabetes. Soon thereafter, recombinant human IL-1β was shown to account

for the death of the β-cell while sparing the α-cell 83. The topic has been CYTH4 reviewed by Mandrup-Poulsen and co-workers, Mandrup-Poulsen being responsible for the original studies 84. Initially, IL-1 was considered to play a pathogenic role primarily in type 1 diabetes, but a role for IL-1β in type 2 diabetes was not appreciated at that time. However, from the studies of Donath et al., IL-1β was implicated in type 2 diabetes, which supported the concept that type 2 diabetes is a chronic inflammatory disease (reviewed in 84). In fact, it was shown that high concentrations of glucose stimulated IL-1β production from the β-cell itself 85 resulting in β-cell death and progressive loss in β cell mass. Relevant to the pathogenesis of type 2 diabetes, glucose-induced IL-1β from the β-cell is enhanced by the presence of free fatty acids. Fundamental to IL-1β-mediated loss of β cell mass is the metabolic upheaval of over-nutrition and obesity and there studies show that the adipocyte in the distant fat stores contributes to the loss of the β-cells 86. The loss of the β cell by IL-1β can also be mediated by oligomers of islet amyloid polypeptide, a protein that forms amyloid deposits in the pancreas during type 2 diabetes, triggering NLRP3 and generating mature IL-1β 87.