TNF and rheumatoid arthritis: High levels of circulating TNF-α, produced primarily by activated macrophages and T cells and, to a lesser extent, by neutrophils, mast cells, and endothelial cells [52], lead to fibroblast activation in RA patients, resulting in the recruitment of inflammatory cells into the lesion and the NF-κB-mediated secretion of inflammatory cytokines, cathepsins, matrix metalloproteinases, and other inflammatory mediators, which cause destructive changes in the joints [53].