Fig. 6

Schematic representation of certolizumab pegol (CZP) action on transmembrane TNF (tmTNF) and subsequent regulation. The Anti-TNF agent CZP induces rapid reactive oxygen species (ROS) production through its binding to tmTNF-α. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is translocated to the nucleus. Heme oxygenase 1 (HO-1) and CD36 are induced. The toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS), which mimics some of the triggers of rheumatoid arthritis (RA), induces strong production of ROS and IL-1β, which are both inhibited by pretreatment with CZP