Summary
For decades inflammation was understood as a single process that simply "wore off" once the trigger was removed. Resolution was passive — what happened when nothing more was happening. The Serhan lab at Harvard, beginning in the late 1990s, established that resolution is a distinct, actively-driven phase with its own bioactive mediators.
The paradigm shift
Inflammation now has two phases. The initiation phase releases pro-inflammatory eicosanoids (prostaglandins via COX, leukotrienes via 5-LOX). After hours to days, the SAME enzymes class-switch to producing specialized pro-resolving mediators (SPMs) — lipoxins, resolvins, protectins, maresins. These actively call leukocyte trafficking off, promote efferocytosis (clearance of apoptotic neutrophils by macrophages), and restore tissue homeostasis.
Why it matters
When the resolution phase fails, inflammation persists as "smouldering" chronic inflammation — implicated in IBD, cardiovascular disease, neurodegeneration, and metabolic syndrome. Anti-inflammatory drugs target initiation; pro-resolving interventions target completion.
Open questions
What clinical biomarkers reliably indicate resolution-phase failure? Can we restore SPM production pharmacologically without omega-3 supplementation? Does the human resolution-defect phenotype have genetic substrate?