====== Inflammation — Episode 4: Cytokines & Chronic Inflammation ======

This episode explains **why some diseases never turn off**.

Acute inflammation protects you.  
Chronic inflammation becomes the disease.

The difference is cytokine signaling.

<WRAP center round important 90%>
Acute inflammation is chemistry.  
Chronic inflammation is immune programming.
</WRAP>

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===== Watch the Lecture =====

<WRAP lecturevideo>
{{youtube>VIDEO_ID_HERE}}
</WRAP>

<WRAP center round important 60%>
📄 **Download Slides (PDF)** \\ 
{{:office_hours:inflammation:episode_4_cytokines.pdf|Download Slides}}
</WRAP>

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===== From Local Reaction → System Disease =====

After the early inflammatory mediators fade, the immune system decides:

  * Stop and repair  
  * Continue and attack  

When cytokines remain active → inflammation sustains itself.

This is the basis of autoimmune disease.

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===== The Major Cytokines =====

<WRAP center 95%>
^ Cytokine ^ Major Role ^ Associated Diseases ^
| TNF-α | Master inflammatory amplifier | RA, IBD, psoriasis |
| IL-1 | Fever and systemic inflammation | Autoinflammatory syndromes |
| IL-6 | Acute phase response | RA, systemic inflammatory disease |
| IL-5 | Eosinophils | Allergic asthma |
| IL-4 / IL-13 | IgE & allergy signaling | Atopic disease |
| IL-17 | Neutrophil activation | Psoriasis, spondyloarthritis |
</WRAP>

These do not cause symptoms briefly — they **reprogram tissue behavior**.

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===== Why NSAIDs Fail in Autoimmune Disease =====

NSAIDs block prostaglandins.

Autoimmune disease is driven by:

→ Immune cell activation  
→ Cytokine signaling  
→ Gene transcription

So NSAIDs reduce pain…  
but disease continues progressing.

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===== Drug Levels of Control =====

<WRAP center 95%>
^ Level ^ Drug Types ^ Effect ^
| Symptom | NSAIDs, antihistamines | Feel better |
| Broad suppression | Corticosteroids | Disease quiets temporarily |
| Immune modification | DMARDs | Disease slows |
| Targeted control | Biologics & JAK inhibitors | Disease mechanism blocked |
</WRAP>

<WRAP center round box 90%>
The higher the level — the closer you are to the cause.
</WRAP>

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===== Why Biologics Feel Different =====

Biologics do not suppress inflammation generally.

They block specific signals:

  * Anti-TNF → stops amplification
  * Anti-IL-5 → removes eosinophils
  * Anti-IL-4/13 → stops allergic signaling
  * JAK inhibitors → block cytokine communication

This is why they can succeed where steroids fail long-term.

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===== Clinical Translation =====

^ Condition ^ Mechanism Level ^
| Osteoarthritis | Local mediator inflammation |
| Rheumatoid arthritis | Cytokine immune disease |
| Asthma (allergic) | Eosinophilic cytokine disease |
| Psoriasis | T-cell cytokine disease |
| Sepsis | Systemic cytokine storm |

Treatment success depends on matching the level.

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===== Key Takeaway =====

<WRAP center round important 90%>
You are not treating inflammation.

You are choosing which conversation in the immune system to interrupt.
</WRAP>

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===== End of Series =====

Return to the overview:

→ [[office_hours:inflammation:start|Inflammation Series Home]]

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===== Related =====

  * [[rheum:start|Rheumatology & Immunosuppressants]]
  * [[respiratory:asthma:start|Asthma Pharmacology]]
  * [[immunology:biologics:start|Biologic Therapies]]
  * [[lectures:start|Full Lecture Series]]