¶ Eicosanoid Class Switch
Type: Enzymatic process / temporal transition
Timeframe: 12–24 hours post-inflammatory stimulus
Key enzyme: 15-LOX (rate-limiting)
Substrates: Arachidonic acid (omega-6) → EPA/DHA (omega-3)
Products: Prostaglandins/Leukotrienes → Resolvins/Protectins/Maresins
¶ Definition
The eicosanoid class switch (also called Lipid mediator class switching) is the temporal and enzymatic transition from pro-inflammatory eicosanoids (Prostaglandins, leukotrienes) derived from omega-6 arachidonic acid to Specialized pro-resolving mediators (SPMs) (Resolvins, Protectins, Maresins) derived from Omega-3 fatty acids (EPA/DHA). This switch is essential for inflammatory resolution.
¶ The Switch — Step by Step
¶ When the switch fails
¶ Mechanism
During acute inflammation initiation, COX-2 and 5-LOX convert arachidonic acid (omega-6) to Prostaglandins (PGE2, PGD2) and leukotrienes (Leukotriene B4). As inflammation progresses, several mechanisms trigger the class switch: (1) Prostaglandin signalling upregulates 15-LOX enzyme; (2) COX-2 becomes substrate-redirected toward Omega-3 fatty acids; (3) 15-LOX converts EPA/DHA to Resolvins, Protectins, and Maresins; (4) These SPMs actively terminate neutrophil infiltration, enhance Efferocytosis, and promote wound healing while stopping further eicosanoid production.
¶ Clinical Significance
Failed or delayed Lipid mediator class switching is a hallmark of chronic inflammation and non-resolving inflammatory conditions. In cPNI practice, supporting this switch through Omega-3 supplementation, reducing omega-6 excess, and addressing metabolic factors that impair LOX enzymes (Oxidative Stress, Insulin) is fundamental to resolution-based therapeutics.
¶ Key Facts
- Switch typically occurs 12–24 hours post-inflammatory stimulus in acute inflammation
- Requires omega-6:Omega-3 ratio <4:1 for efficient switching
- 15-LOX enzyme is rate-limiting for SPM biosynthesis
- Obesity and diabetes impair class switching through altered enzyme expression
- Aspirin modifies COX-2 to preferentially produce Aspirin-triggered resolvins (aspirin-triggered)
¶ Connections
- Lipid mediator class switching — synonymous terms for the same process
- Specialized pro-resolving mediators (SPMs) — end products of the eicosanoid class switch
- Arachidonic acid — source of pro-inflammatory eicosanoids in early inflammation phase
- EPA — Omega-3 substrate for Resolvins after class switch
- DHA — Omega-3 substrate for Protectins and Maresins after class switch
- 15-LOX — key enzyme enabling conversion of Omega-3 to SPMs
- Resolution indices — class switch timing determines resolution interval (Ri)
¶ Module References
- Module 1
- Module 5