The generation of reactive oxygen species is a central feature of inflammation that results in the oxidation of host phospholipids. Endogenously formed oxidized phospholipids, such as 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (OxPAPC), have been shown to inhibit TLR4- & TLR2-mediated signaling induced by bacterial lipopeptide or lipopolysaccharide (LPS) in various human cells (Bochkov VN et al., 2002; von Schlieffen E et al., 2009). Oxidized phospholipids were found to bind LPS binding protein (LBP) and soluble CD14 suggesting that the binding prevented recognition of LPS by these proteins thus preventing recognition of LPS and activation of TLR4 (Erridge C et al., 2008; von Schlieffen E et al., 2009). In addition, oxPAPC protected mice treated with a lethal dose of LPS (Bochkov VN et al., 2002). Thus, oxidized phospholipids may function as a negative feedback to blunt innate immune responses.