However, anti-inflammatory cytokines and cytokine inhibitors are also present in large quantities in RA joints. IL-10, produced by macrophages and partly by T cells in the synovial tissue (ST), is best known as a negative regulator for macrophage and Th1 cells, but the expression level is insufficient to counterbalance the cascade of proinflammatory events [12]. In addition, the anti-inflammatory action of IL-10 appears to be modulated at the level of signal transduction during chronic inflammation. IL-10 signaling is impaired in macrophages upon chronic exposure to proinflammatory cytokines such as TNF-α and IL-1 and immune complexes [13,14]. Cell surface expression of IL-10R1 is decreased in synovial fluid dendritic cells due to the presence of TNF-α, IL-1, and granulocyte–macrophage colony-stimulating factor [15].