Immunosuppressants are essential in managing autoimmune diseases and preventing organ transplant rejection. This crash course post simplifies the topic by focusing on the most high-yield points and memory hacks—especially around the IL-2 pathway, which is central to understanding how these drugs work.
🔬 The IL-2 Pathway: The Backbone of Immune Suppression
Most immunosuppressants target the IL-2 pathway, so let’s break it down step-by-step:
- Toll-like receptor (TLR) is activated by infection or inflammation.
- TLR stimulates calcineurin.
- Calcineurin dephosphorylates NFAT-P → NFAT, activating:
- NF-κB, a transcription factor that leads to:
- IL-2 and inflammatory cytokine production.
🧠 Why IL-2?
Because it stimulates T-cell proliferation—so blocking it = immune suppression.
🔒 Calcineurin Inhibitors (CNIs)
Cyclosporine and Tacrolimus inhibit calcineurin, preventing IL-2 transcription.
Drug | Binding Partner | Mnemonic |
---|---|---|
Cyclosporine | Cyclophilin | Cyclo-lovin’ Cyclosporine |
Tacrolimus | FKBP (FK506) | Tacro = Smart = Brainy |
🔴 Cyclosporine Side Effects
- Nephrotoxicity 🚰
- Hypertension 💢
- Hirsutism 🧔♀️
- Gingival hyperplasia 🦷
🧠 Visual Mnemonic: Imagine a hairy kidney with teeth riding a cycle (Cyclo-sporine).
🔴 Tacrolimus Side Effects
- Neurotoxicity 🧠
- Diabetes Mellitus 🍬
- Also nephrotoxic
🧠 Mnemonic: Tacro sounds smart = brain toxicity (neurotoxicity)
🚫 mTOR Inhibitor: Sirolimus
Acts after IL-2 binds to its receptor. It blocks the mTOR pathway, preventing IL-2 signal transmission.
🧠 Mnemonic:
Siro → “RO” → blocks IL2R → mTOR
Or just remember: Sigh of relief with Sirolimus — but it comes with…
🔴 Sirolimus Side Effects
- Pancytopenia (↓WBC, RBC, Platelets) 🩸
- Hyperlipidemia 🩺
- Hyperglycemia 🧁
- Not nephrotoxic (safe for kidneys)
🧠 Visual Mnemonic: A “sigh” stabbing red/white cells but sparing the kidney.
🌿 Basiliximab: IL-2R Blocker
A monoclonal antibody that directly blocks IL-2 receptors (IL2R) to prevent T-cell activation.
🧠 Mnemonic: Basil seeds blocking a drink straw = Basiliximab blocking IL2R
🧪 Summary Table
Drug | Target | Key Side Effects |
---|---|---|
Cyclosporine | Calcineurin (via cyclophilin) | Nephrotoxicity, hirsutism, gingival hyperplasia |
Tacrolimus | Calcineurin (via FKBP) | Neurotoxicity, diabetes, nephrotoxicity |
Sirolimus | mTOR | Pancytopenia, hyperlipidemia, not nephrotoxic |
Basiliximab | IL-2R | Minimal, infusion-related |
💊 Clinical Tips
- Avoid CNIs in patients with kidney issues—consider Sirolimus instead.
- Always monitor glucose, lipids, and CBC in long-term use.
- Use visual mnemonics to solidify the pathways in your memory.