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Inflammation — Episode 2: The Arachidonic Acid Pathway
This episode explains the central chemical engine of inflammation.
Most everyday drugs patients recognize — ibuprofen, aspirin, steroids, montelukast — all work somewhere on this single pathway.
If Episode 1 was the map, this is the highway everything travels on.
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Step 1 — Membrane Activation
All inflammation begins with cell membrane phospholipids.
Damage or immune activation triggers:
→ Phospholipase A₂
This releases:
→ Arachidonic Acid
No arachidonic acid = no inflammatory mediators
Drug that blocks this step:
- Corticosteroids
This is why steroids feel dramatically stronger than NSAIDs.
Step 2 — Two Competing Pathways
Once arachidonic acid exists, it must choose a direction:
| Pathway | Enzyme | Products | What They Do |
|---|---|---|---|
| COX Pathway | Cyclooxygenase | Prostaglandins & Thromboxane | Pain, fever, swelling |
| LOX Pathway | Lipoxygenase | Leukotrienes | Bronchoconstriction, mucus, asthma |
Every common anti-inflammatory drug targets one of these branches.
COX Pathway (Pain & Fever)
Produces Prostaglandins (PGE₂, PGI₂) and Thromboxane (TXA₂)
Clinical effects:
- Pain sensitization
- Fever generation
- Vasodilation
- Platelet activation
Blocked by:
- Aspirin
- COX-2 selective inhibitors
Patients experience:
- ↓ pain
- ↓ fever
- ↓ swelling
But NOT immune suppression.
LOX Pathway (Airway Inflammation)
Produces Leukotrienes (LTB₄, LTC₄, LTD₄, LTE₄)
Clinical effects:
- Bronchoconstriction
- Airway edema
- Mucus secretion
- Eosinophil recruitment
Blocked by:
Important insight:
Asthma is not a prostaglandin disease — it is primarily a leukotriene disease.
Why Steroids Are Different
Steroids block:
→ Phospholipase A₂ (upstream of BOTH pathways)
So they reduce:
- Prostaglandins
- Leukotrienes
- Cytokines
- Immune cell migration
NSAIDs turn off one faucet Steroids shut off the water main
Clinical Consequences
| Drug Class | What Improves | What Does NOT Improve |
|---|---|---|
| Antihistamines | Itch & allergy | Pain & arthritis |
| NSAIDs | Pain & fever | Asthma control |
| Leukotriene blockers | Asthma | Arthritis pain |
| Steroids | Almost everything | Long-term safety |
Understanding failures becomes predictable.
Key Takeaway
You cannot treat leukotriene disease with prostaglandin drugs — and you cannot treat immune disease with symptom drugs.