Suggested role of cytokines in the pathogenesis of synovial independent blood-induced cartilage damage. Monocyte/macrophages activated by the phagocytosis of erythrocytes produce IL-1β and TNFα, which both induce the production of proteases causing reversible cartilage damage (striped arrows). IL-1β also induces the production of IL-6 and IL-1β itself (gray arrows). These cytokines are able to activate the chondrocyte to produce hydrogen peroxide (H₂O₂), which in the presence of iron leads to the production of hydroxyl radicals (OH·) causing chondrocyte apoptosis and as such irreversible cartilage damage, whereas TNFα does not. Local inhibition of IL-1β (directly in case of major surgery) or within the same day (in case of trauma or hemophilia-induced joint bleeds) may provide a mechanism to prevent cartilage damage and with that joint destruction later on.