Summary
Conceptually one of the most important paradigm shifts in inflammation research in the past 15 years, led by Charles Serhan at Harvard. Resolution of inflammation is not a passive process — it is an active, biochemically driven phase with its own mediator molecules.
The biology
Specialized pro-resolving mediators (SPMs) include resolvins, protectins, and maresins — bioactive metabolomes that stimulate self-limited innate responses, enhance microbial killing and clearance, and are organ-protective.
SPMs are bioactive lipid mediators derived from omega-3 fatty acids — specifically arachidonic acid (AA), EPA, and DHA. Lipoxins come from AA, E-series resolvins from EPA, and D-series resolvins, protectins, and maresins from DHA.
Core principle
When inflammation begins, the system releases pro-inflammatory eicosanoids (PGE2, LTB4). Over hours, the same enzymes (COX, LOX) must switch to producing resolvins instead. This class-switch requires sufficient EPA and DHA in cell membranes. When omega-3 status is low, the system continues producing pro-inflammatory mediators rather than resolvins — and inflammation never enters resolution.
Clinical implication
In a patient with chronic escalating inflammation, this may partly explain "why doesn't it ever stop?" Measurement of omega-3 index (% EPA+DHA in red blood cell phospholipids) is a standardized blood test. Optimal: >8%. Most Western populations: 3–5%. Directly measurable and modifiable.
Open questions
Direct SPM administration (Resolvin E1, Resolvin D2) is being studied as pharmacological intervention. Still mostly preclinical but one of the most active translational fields. Whether downstream resolvin biology can be triggered without omega-3 substrate is the active question.