Specialized pro-resolving mediators (SPMs)

Specialized pro-resolving mediators (SPMs) are a superfamily of endogenous bioactive lipid signaling molecules derived from polyunsaturated fatty acids, primarily omega-3 fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Unlike traditional anti-inflammatory agents that inhibit the initiation of inflammation, SPMs actively orchestrate the resolution phase by binding to specific G protein-coupled receptors (GPCRs) such as FPR2/ALX, GPR32, and ChemR23. Their primary biological roles include limiting further neutrophil recruitment, promoting the non-phlogistic recruitment of monocytes, and enhancing the clearance of apoptotic cells and debris by macrophages, a process known as efferocytosis. Dysregulation or deficiency in SPM biosynthetic pathways is linked to the progression of chronic inflammatory conditions, including atherosclerosis, Alzheimer's disease, rheumatoid arthritis, and metabolic syndrome. Therapeutic strategies targeting these pathways involve the administration of omega-3 precursors, aspirin (which triggers the synthesis of epimeric "aspirin-triggered" SPMs), or synthetic SPM analogs designed for greater metabolic stability. These approaches aim to restore tissue homeostasis and promote healing without the immunosuppressive side effects associated with corticosteroids or NSAIDs. Research continues to explore their potential in managing chronic pain and enhancing host defense against infections by reprogramming the immune response rather than simply suppressing it.

Other names

Pro-resolving lipid mediatorsOmega-3 derived specialized pro-resolving mediatorsResolvinsProtectinsMaresinsLipoxins

Activation of specific G protein-coupled receptors (e.g., FPR2/ALX, GPR32, ChemR23) to inhibit neutrophil infiltration, enhance macrophage-mediated efferocytosis of apoptotic cells, and suppress pro-inflammatory cytokine production.