Levels of hydrogen peroxide in tissues adjacent to failing implantable devices may play an active role in cytokine production.

Late aseptic loosening of total joint implants continues to be a common cause of implant failure. However, the pathophysiology of implant loosening remains controversial as to which factors at the implant tissue interface plays a crucial role in implant failure. The most prominent features of the foreign body membrane obtained from patients undergoing revision hip surgery were the presence of lymphocytes, histiocytes, giant cells, and immature collagen formation. Biochemical and immunochemical analysis of the tissues revealed increased levels of pro-inflammatory cytokines as well as increased levels of hydrogen peroxide and decreased activity of catalase Increasing concentrations of hydrogen peroxide also caused increases in macrophage release of pro-inflammatory cytokine (IL-1). Macrophage activation by cytokine (TNF alpha) or lipopolysaccharide (LPS) is mediated via translocation of NF kappa B from the cytosol to the nucleus and appears to be dependent upon phospholipase D (PLD). In tissues of patients with aseptic loosening of implants, over production of hydrogen peroxide in response to wear debris stimuli, may activate NF kappa B and initiate cytokine production.