Pro-Resolving Lipid Mediators in Inflammatory Processes

Inflammation is a vital immune response to injury or infection, yet its timely resolution is equally critical to prevent chronic pathology. Pro-resolving lipid mediators are a class of endogenously produced molecules derived from omega-3 and omega-6 polyunsaturated fatty acids that orchestrate the active termination of inflammation and promote tissue repair. These mediators, which include resolvins, protectins and maresins, function by limiting neutrophil recruitment, enhancing macrophage-mediated clearance of apoptotic cells (efferocytosis) and reprogramming immune cells towards pro-repair phenotypes. By restoring homeostasis, they counterbalance pro-inflammatory eicosanoids and cytokines, thereby reducing oxidative stress, necrosis and fibrosis. The broad spectrum of actions exhibited by pro-resolving lipid mediators underpins their protective roles in cardiovascular health, arthritis, neuroinflammation and pulmonary disorders, highlighting their global significance and translational potential as novel therapeutic agents.

Research from Nature Portfolio

Recent studies have illuminated novel mechanisms by which specialised mediators steer resolution. One investigation demonstrated that administration of a 13-series resolvin markedly reduces atherosclerotic burden in murine inflammatory arthritis by activating cholesterol efflux in lipid-laden macrophages via a scavenger receptor-dependent pathway, thereby reprogramming these cells toward tissue protection. Another foundational work revealed that vulnerable regions of human atherosclerotic plaques exhibit a diminished ratio of specialised pro-resolving mediators to pro-inflammatory leukotrienes. Restoration of this balance through resolvin treatment improved plaque stability, enhanced efferocytosis and thickened fibrous caps in preclinical models, providing mechanistic support for targeted SPM therapy in cardiovascular disease.

Pro-Resolving Lipid Mediators in Inflammatory Processes publication trend

The graph below shows the total number of articles in pro-resolving lipid mediators in inflammatory processes across all publications each year (not limited to Nature Index journals).

Technical terms

Specialised pro-resolving mediators (SPM): Endogenous lipid compounds including resolvins, protectins and maresins that actively orchestrate the resolution phase of inflammation.

Resolvin: A subclass of SPM derived from omega-3 fatty acids that limits neutrophil infiltration and promotes clearance of cellular debris.

Protectin: A family of docosahexaenoic acid-derived mediators that protect tissues from excessive inflammation and support cell survival.

Maresin: Macrophage-derived mediators biosynthesised from DHA that enhance phagocytosis and tissue regeneration.

Efferocytosis: The process by which phagocytes engulf and remove apoptotic cells, a key step in resolving inflammation.

References

1. Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease. Nature Communications (2024).
2. An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques. Nature Communications (2016).
3. Bioactive Lipids and Chronic Inflammation: Managing the Fire Within. Frontiers in Immunology (2018).
4. Novel Docosatrienes and 17S-Resolvins Generated from Docosahexaenoic Acid in Murine Brain, Human Blood, and Glial Cells AUTACOIDS IN ANTI-INFLAMMATION*. Journal of Biological Chemistry (2003).
5. Resolvin D1 and Its Aspirin-triggered 17R Epimer STEREOCHEMICAL ASSIGNMENTS, ANTI-INFLAMMATORY PROPERTIES, AND ENZYMATIC INACTIVATION*. Journal of Biological Chemistry (2007).