S100A4 has also been shown to stimulate the production of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α from peripheral blood mononuclear cells (PBMC) isolated from patients with rheumatoid arthritis; however, these effects were not RAGE-dependent, but TLR-4-dependent (Table 1) [81]. This evidence concerns the gene AGER and rheumatoid arthritis.