How to use: Record yourself performing both sides. Play it back while walking or commuting. The cheesier your delivery, the better it sticks.
TNF-alpha (aggressive, first on scene):
I'm TNF-alpha, first responder on the block,
Macrophage released me, now the whole system's in shock,
I dilate your vessels, make the endothelium leak,
Call in the neutrophils — we got pathogens to seek!
I activate NF-kappa-B, turn on every gene,
Most potent acute-phase trigger that you've ever seen!
IL-1-beta (backing up TNF):
IL-1-beta in the building, pyrogenic number one,
I crank the thermostat — fever means we've just begun,
Hypothalamus hears me, PGE2 goes high,
Cross the blood-brain barrier — that's sickness behaviour, that's why
You lose your appetite, you sleep, you ache, you moan,
That's not disease, that's ME — helping you heal at home!
IL-6 (the double agent, dramatic entrance):
Hold up — I'm IL-6, I play for BOTH the teams,
Classical signalling: anti-inflammatory dreams,
But when I trans-signal through soluble receptor chains,
I'm the CHRONIC inflammation that drives metabolic pains!
Liver hears my call, pumps out CRP,
Acute phase proteins rising — that's diagnostics, G!
I push T-helper cells from Treg towards Th-17,
One cytokine, two faces — I'm the whole damn machine!
IL-8 (CXCL8) (hype man):
IL-8! Chemokine! Neutrophil sat-nav!
Follow my gradient, boys — this tissue's looking bad!
I guide you to the damage, chemotaxis is my game,
Without me you'd be wandering — lost without a name!
Lipoxin A4 (calm, wise, arrives late):
Enough. I'm Lipoxin A4 — the ceasefire signal,
Derived from arachidonic via the LOX enzymes, original,
I stop neutrophil recruitment at the vascular wall,
Flip the macrophage to M2 — now they clean, not brawl,
You can't heal without me, that's resoleomics fact,
Aspirin triggers my production — that's the therapeutic act.
Resolvin D1 (smooth, omega-3 derived):
Resolvin D1 from DHA, omega-3 is where I'm from,
I don't suppress inflammation — I help it get DONE,
Clear the neutrophil debris, bring the tissue back to peace,
Efferocytosis activated — macrophages feast!
SPMs are the future, resolution is the key,
Pruimboom taught you this — chronic disease starts without me.
Protectin D1 (drops the mic):
Neuroprotectin in the brain, Protectin in the rest,
I guard the neural tissue — neuroprotection at its best,
Anti-apoptotic, I keep your neurons alive,
Without omega-3 in diet? Good luck trying to thrive.
TNF-alpha (back, but tired, low-grade):
Wait... I'm still here... but nobody called me back,
No resolution happened, so I'm stuck on this track,
Low-grade, persistent, just a whisper, not a shout,
But day after day I'm driving insulin resistance out,
Endothelial dysfunction, atherosclerotic plaques,
Depression, neurodegeneration — I'm the silent attack,
This wasn't meant to happen — I was built for the acute,
Without Lipoxins, Resolvins, I'm stuck on a loop.
IL-6 (weary, trans-signalling continuously):
And I'm stuck in trans-signal mode, no one flipped me back,
Feeding low-grade inflammation, metabolic heart attack,
This is evolutionary mismatch at its core —
My off-switch needs omega-3... but you don't eat fish anymore.
| Lyric Reference | Concept | Exam Relevance |
|---|---|---|
| TNF-alpha first responder | TNF-alpha is primary acute-phase cytokine | Module 4, 5 |
| NF-kappa-B activation | TLR-NF-kB pathway drives inflammatory gene transcription | Module 4 |
| IL-1-beta pyrogenic | IL-1-beta + PGE2 = fever via hypothalamus | Module 4 |
| Sickness behaviour | Adaptive immune-driven behavioural response | Module 7 |
| IL-6 dual signalling | Classical (anti) vs trans-signalling (pro) | Module 4, 7 |
| Lipoxin A4 ceasefire | Eicosanoid class switch from PGs to lipoxins | Module 5 |
| Aspirin-triggered lipoxins | Low-dose aspirin enhances resolution | Module 5 |
| Resolvins from DHA | Omega-3 → SPMs → active resolution | Module 5, 10 |
| Efferocytosis | M2 macrophage clearance of apoptotic neutrophils | Module 5 |
| Chronic low-grade loop | Failed resolution = chronic disease mechanism | Module 7 |
| Evolutionary mismatch | Diet change → inadequate SPM production | Module 2 |