The role of phospholipid oxidation products in inflammatory and autoimmune diseases: Evidence from animal models and in humans

Abstract

Since the discovery of oxidized phospholipids (OxPL) and their implication as modulators of inflammation in cardiovascular disease, roles for these lipid oxidation products have been suggested in many other disease settings. Lipid oxidation products accumulate in inflamed and oxidatively damaged tissue, where they are derived from oxidative modification of lipoproteins, but also from membranes of cells undergoing apoptosis. Thus, increased oxidative stress as well as decreased clearance of apoptotic cells has been implied to contribute to accumulation of OxPL in chronically inflamed tissues. A central role for OxPL in disease states associated with dyslipedemia, including atherosclerosis, diabetes and its complications, metabolic syndrome, and renal insufficiency, as well as general prothrombotic states, has been proposed. In addition, in organs which are constantly exposed to oxidative stress, including lung, skin, and eyes, increased levels of OxPL are suggested to contribute to inflammatory conditions. Moreover, accumulation of OxPL causes general immunmodulation and may lead to autoimmune diseases. Evidence is accumulating that OxPL play a role in lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis. Last but not least, a role for OxPL in neurological disorders including multiple sclerosis (MS), Alzheimer’s and Parkinson’s disease has been suggested. This chapter will summarize recent findings obtained in animal models and from studies in humans that indicate that formation of OxPL represents a general mechanism that may play a major role in chronic inflammatory and autoimmune diseases.