Specialized pro-resolving lipid mediators pathway (SPM pathway)

The Specialized Pro-resolving Lipid Mediators (SPM) pathway is a complex biochemical network responsible for the active resolution of inflammation. Unlike traditional anti-inflammatory approaches that inhibit the onset of inflammation, the SPM pathway utilizes endogenous lipid-derived molecules—including lipoxins, resolvins, protectins, and maresins—to signal the termination of the inflammatory response and promote tissue homeostasis. These mediators act through specific G protein-coupled receptors (GPCRs) such as ALX/FPR2, ChemR23, and GPR32 to limit further neutrophil infiltration, enhance macrophage phagocytosis of apoptotic cells (efferocytosis), and reduce pro-inflammatory cytokine production. Dysregulation of this pathway is implicated in chronic inflammatory diseases, including cardiovascular disease, neurodegeneration, and autoimmune disorders. Therapeutic strategies targeting this pathway involve the administration of synthetic SPM analogs or the modulation of biosynthetic enzymes like 15-lipoxygenase to switch on resolution. While promising as immunoresolvents that do not cause global immunosuppression, challenges remain regarding the metabolic stability of lipid analogs and the precise characterization of receptor-ligand interactions in human disease.

Other names

Resolution of inflammation pathwayLipoxin-Resolvin-Protectin-Maresin pathwayEndogenous resolution pathway

Activation of pro-resolving G protein-coupled receptors (GPCRs) such as ALX/FPR2, ChemR23, and GPR32 to promote the resolution of inflammation, enhance macrophage efferocytosis, and inhibit neutrophil infiltration.