Therapeutic Potential of Lipoxin A₄ in Chronic Inflammation: Focus on Cardiometabolic Disease

Several studies have shown that failure to resolve inflammation may contribute to the progression of many chronic inflammatory disorders. It has been suggested targeting the resolution of inflammation might be a novel therapeutic approach for chronic inflammatory diseases, including inflammatory bowel disease, diabetic complications, and cardiometabolic disease. Lipoxins [LXs] are a class of endogenously generated mediators that promote the resolution of inflammation. Biological actions of LXs include inhibition of neutrophil infiltration, promotion of macrophage polarization, increase of macrophage efferocytosis, and restoration of tissue homeostasis. Recently, several studies have demonstrated that LXs and synthetic analogues protect tissues from acute and chronic inflammation. The mechanism includes down-regulation of pro-inflammatory cytokines and chemokines (e.g., interleukin-1β and tumor necrosis factor-α), inhibition of the activation of the master pro-inflammatory pathway (e.g., nuclear factor κ-light-chain-enhancer of activated B cells pathway) and increased release of the pro-resolving cytokines (e.g., interleukin-10). Three generations of LXs analogues are well described in the literature, and more recently a fourth generation has been generated that appears to show enhanced potency. In this review, we will briefly discuss the potential therapeutic opportunity provided by lipoxin A₄ as a novel approach to treat chronic inflammatory disorders, focusing on cardiometabolic disease and the current drug development in this area.