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:

NSAIDs
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:

Leukotriene Modifiers

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.

Next Episode

→ Episode 3 — Histamine & Immediate Hypersensitivity