Reprogramming inflammation: Mechanisms and therapeutic targeting of eicosanoids and pro-resolving mediators.
Level 5 - mechanism / opinion, no new human data
Narrative review of mechanisms and therapeutic targets with no original human empirical data.
PubMed 40623536 · doi:10.1016/j.ejphar.2025.177924
What was done
The authors synthesized existing literature on the enzymatic pathways regulating eicosanoid and specialized pro-resolving mediator (SPM) biosynthesis (including PLA2, COX, LOX, and CYP/sEH pathways), cellular mechanisms driving inflammatory resolution, and current resolution-based therapeutic strategies.
What was found
The abstract provides no quantitative experimental numbers. It outlines that bioactive lipid mediators generated from arachidonic acid and polyunsaturated fatty acids govern both inflammation onset (e.g., prostaglandins, leukotrienes) and its active resolution (e.g., lipoxins, resolvins, protectins, maresins). SPMs actively drive tissue repair and immunomodulation at picomolar to nanomolar concentrations, and the CYP-derived epoxyeicosatrienoic acid (EET)/soluble epoxide hydrolase (sEH) axis represents a key regulatory node. The clinical relevance of aspirin-triggered epimeric SPMs remains under investigation.
Why it matters
Understanding active resolution pathways rather than solely blocking pro-inflammatory pathways highlights novel pharmacological targets (such as PLA2, sEH, and direct SPM agonists) for treating chronic inflammatory conditions like arthritis, atherosclerosis, and cancer.
Limits
This is a narrative review presenting mechanistic overviews without primary clinical trial data, systematic search criteria, or meta-analytic quantification. The clinical applicability, optimal dosing, and therapeutic feasibility of targeting these pathways in humans remain to be established.
Cited by
- supports Lipoxin A is an anti-inflammatory specialized pro-resolving mediator synthesized from arachidonic acid.