While blood itself may not persist in the joint space, the remnants of erythrocytes including hemoglobin and deposited iron (hemosiderosis) may have longer-lasting or permanent effects as heme interacts with immune and synovial cells to induce the production of pro-inflammatory cytokines (e.g., IL-1 and TNFα) as well as fibroblast proliferation leading to tissue hyperplasia [49,52]. This evidence concerns the gene IL1B and hemosiderosis.