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Researchers from Washington State University have shown that inhibition of tumor growth factor-β (TGF-β)-activated kinase 1 (TAK1) can effectively downregulate inflammatory mediators and suppress inflammation caused by gout.
Monosodium urate (MSU) crystals directly activate the inflammasome to produce a plethora of pro-inflammatory cytokines, including interleukin-1β (IL-1β).
In an animal model of gout, researchers showed that MSU crystals significantly amplified IL-1β-induced production of IL-6, IL-8, and ENA-78/CXCL5 production. However when they administered an inhibitor of TAK1, 5Z-7-oxozeaenol, in MSU-induced paw inflammation in C57BL/6 mice, they noted rapid and sustained improvement in inflammation in this paper published in Cellular & Molecular Immunology.
While MSU-induced proinflammatory cytokine production was completely inhibited by 5Z-7-oxozeaenol, suggesting that TAK1 is an important mediator of MSU-induced inflammation.
This discovery has potential as a new treatment strategy for gout. Moreover, the authors postulate that this method of IL-1 inhibition may be as multiple sclerosis, inflammatory bowel disease, type 1 diabetes, etc.