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Mediators

Specialized pro-resolving mediators (SPMs)

Hypothesis Mechanism review
mechanism inflammation supplement marker ernæring
Editor's note
Persistent inflammation in chronic disease often reflects a failure to actively resolve, not merely to initiate—and specialized pro-resolving mediators derived from omega-3 fatty acids appear central to that resolution process. This foundational review maps four SPM families and their receptor pathways, representing the maturing but still-emerging evidence base underpinning clinical trials and dietary interventions. Gastroenterologists, rheumatologists, and neurologists should engage this framework to understand why resolution biology could reshape how we treat inflammatory conditions.

Summary

SPMs are bioactive lipid metabolites derived from polyunsaturated fatty acids. They include four families: lipoxins (from arachidonic acid), E-series resolvins (from EPA), D-series resolvins (from DHA), protectins (from DHA), and maresins (from DHA via macrophage routes).

The lipid pathways

Lipoxins (LXA4, LXB4) — derived from AA via sequential LOX action. First-described SPMs (1984). Stop neutrophil chemotaxis, stimulate monocyte recruitment for clearance.

E-series resolvins (RvE1, RvE2, RvE3) — from EPA. Most studied: RvE1 binds the ChemR23 receptor on neutrophils to halt chemotaxis.

D-series resolvins (RvD1–RvD6) — from DHA. RvD1 and RvD2 have received the most clinical interest.

Protectins (PD1/NPD1, PDX) — from DHA. Strong neuroprotective effects; PD1 reduces glutamate excitotoxicity.

Maresins (MaR1, MaR2) — from DHA via macrophages. Promote tissue regeneration, distinct from other SPMs in driving M2 macrophage polarization.

Clinical translation

Several SPMs are in early-phase human trials (notably RvE1 for ocular inflammation). Most clinical interest currently focuses on raising endogenous SPM production via omega-3 substrate rather than direct administration.

Open questions

Which SPMs are produced in which tissues at which time-points? Are some SPMs functionally interchangeable or do specific deficits cause specific phenotypes? Why are SPM doses needed for clinical effect so much smaller than typical drug doses?

Related articles in this corpus

Extends
Resolution biology — SPMs (resolvins, protectins, maresins)
Article B provides the detailed biochemical and molecular taxonomy of SPM families that Article A introduces conceptually as the active mediators of inflammation resolution.
Extends
Resolution as an active process
Article B provides the molecular mechanism and specific bioactive mediators (SPMs) that constitute the active resolution process described conceptually in Article A.
Extends
The omega-3 index as biomarker
Article B provides a clinical measurement tool to quantify the precursor substrates (EPA and DHA) that directly determine the production capacity of the SPM families described in Article A.
Parallel
Metformin-phytochemical combination therapy in metabolic dysfunction-associated steatotic liver disease: mechanistic insights and therapeutic potential
Both articles address inflammatory and metabolic dysfunction through lipid-based mechanisms, but operate in distinct therapeutic contexts—SPMs as endogenous pro-resolving mediators versus metformin-phytochemical modulation of metabolic pathways in liver disease.
Parallel
Emapunil attenuates ulcerative colitis by suppressing Z-DNA binding protein 1 driven pyroptosis and pro-inflammatory polarization in macrophages
Both articles address inflammation resolution in different contexts—Article A describes SPMs as resolution mediators at the biochemical level, while Article B examines macrophage-driven inflammation in UC—but lack direct mechanistic overlap.
Published 2026-05-25 · Last kit-update 2026-05-25