Specialized pro-resolving lipid mediators (SPM)

Specialized pro-resolving lipid mediators (SPMs) are a genus of endogenous bioactive lipids derived from essential polyunsaturated fatty acids (PUFAs), including arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). They comprise four major families—lipoxins, resolvins, protectins, and maresins—which function as "resolution agonists" to actively coordinate the termination of the inflammatory response and the restoration of tissue homeostasis. Unlike traditional anti-inflammatory drugs that inhibit the initiation of inflammation, SPMs act on specific G protein-coupled receptors (GPCRs) to limit further neutrophil infiltration, enhance the clearance of apoptotic cells by macrophages (efferocytosis), and promote tissue regeneration. Dysregulation or deficiency in SPM production is associated with various chronic inflammatory and metabolic conditions, such as atherosclerosis, asthma, and neurodegenerative diseases. Pharmacological efforts focus on developing synthetic SPM mimetics and stable analogs to treat chronic inflammatory diseases without inducing global immunosuppression.

Other names

Specialized proresolving mediatorsPro-resolving lipid mediatorsLipoxinsResolvinsProtectinsMaresinsEndogenous immunoresolvents

Agonism of specific pro-resolving G protein-coupled receptors (including FPR2/ALX, GPR32, GPR18, ChemR23, and GPR37) to actively trigger the resolution phase of inflammation and enhance macrophage-mediated clearance of cellular debris.