STEPTRACKERIMMUNOLOGY + PHARMACOLOGY | ADAPTIVE IMMUNITY | HIGH-YIELD REVIEW

Cytokines

Cytokines are the immune system's messages — who makes each one, what it does, and the drug that blocks or replaces it.

FOCUS ON
Macrophage-derived (innate): IL-1 (fever, endothelial activation), IL-6 (fever, acute-phase proteins), TNF-α (fever, cachexia, septic shock, granuloma maintenance), IL-8 (neutrophil chemotaxis), IL-12 (Th1, NK). T-cell-derived: IL-2 (T-cell growth), IL-3 (marrow), IL-4 (Th2, IgE), IL-5 (eosinophils, IgA), IL-10 (anti-inflammatory), IL-13 (IgE, mucus), IL-17 (neutrophils), IFN-γ (macrophages, MHC). Interferons α/β: antiviral. TGF-β: suppression, fibrosis. Signal mostly through JAK–STAT (tofacitinib, baricitinib). Shared γ chain (IL-2, 4, 7, 9, 15, 21 receptors) → X-linked SCID.
CYTOKINE
MAIN SOURCE
MAIN ACTIONS
DRUG · DISEASE
IL-1
Macrophages (inflammasome)
Fever, endothelial adhesion molecules, acute inflammation
Anakinra (IL-1R antagonist), canakinumab · periodic fevers, gout
IL-6
Macrophages, endothelium, T cells
Fever, hepatic acute-phase proteins (CRP, hepcidin), Th17
Tocilizumab (IL-6R) · cytokine release syndrome, giant cell arteritis
TNF-α
Macrophages, T cells
Fever, cachexia, vascular leak, neutrophil activation, granuloma maintenance
Infliximab, adalimumab, etanercept · reactivates TB
IL-8 (CXCL8)
Macrophages, endothelium
Neutrophil chemotaxis
—
IL-12
Macrophages, DCs
Th1 differentiation, NK activation
Ustekinumab (IL-12/23 p40) · IL-12R defect → mycobacteria
IL-2
T cells
T-cell (and NK, Treg) proliferation
Aldesleukin (melanoma, RCC) · capillary leak · basiliximab blocks IL-2R
IL-3 · GM-CSF · G-CSF
T cells, stromal cells
Marrow growth and differentiation
Filgrastim (G-CSF), sargramostim (GM-CSF) for neutropenia
IL-4 · IL-13
Th2 cells, mast cells
Th2 differentiation, IgE class switch, mucus
Dupilumab (IL-4Rα) for atopic dermatitis, asthma
IL-5
Th2 cells
Eosinophil growth and activation; IgA
Mepolizumab, benralizumab (eosinophilic asthma, EGPA)
IL-10 · TGF-β
Tregs, macrophages
Suppress inflammation, ↓ MHC II · TGF-β drives fibrosis and IgA
IL-10 receptor defect → infantile IBD
IL-17 · IL-23
Th17 cells · macrophages/DCs
Neutrophil recruitment, epithelial antimicrobials; IL-23 sustains Th17
Secukinumab, ixekizumab (IL-17), guselkumab (IL-23) for psoriasis
IFN-γ
Th1, NK, CD8⁺ cells
Activates macrophages, ↑ MHC I and II, Th1, IgG switch, granulomas
IFN-γ therapy for CGD · IGRA test measures it
IFN-α · IFN-β
Infected cells, plasmacytoid DCs
Antiviral state, ↑ MHC I, NK activation
IFN-β for MS · IFN-α (historic HBV/HCV) · high in SLE

Mechanism — JAK–STAT signaling

Cytokine binds receptor
→
JAKs phosphorylate
→
STATs dimerize → nucleus
→
Gene expression

JAK inhibitors (tofacitinib, baricitinib, upadacitinib) block many cytokines at once → zoster, thrombosis risk. STAT3 loss → hyper-IgE syndrome; γc/JAK3 loss → SCID.

Fever and inflammation trio

CYTOKINE
SIGNATURE ACTION
BLOCKER
IL-1
Fever, inflammasome output
Anakinra
IL-6
Acute-phase proteins
Tocilizumab
TNF-α
Shock, cachexia, granulomas
Infliximab

How it's tested

COMMON CONFUSIONIL-5 (eosinophils) vs IL-4 (IgE class switch) — both Th2, both targeted in asthma, by different antibodies.
THE TRAPBefore any TNF-α inhibitor, screen for latent TB — TNF holds granulomas together.
YOUR APPROACHCytokine → source cell → target cell and action → disease when excessive → drug that blocks it.

If you see… think…

Hepatic CRP and hepcidin production → IL-6
Weight loss and muscle wasting in chronic disease → TNF-α (cachexia)
Neutrophil chemotactic cytokine → IL-8
T-cell growth factor → IL-2
Eosinophil growth and activation → IL-5
Macrophage activation in granulomas → IFN-γ
Anti-inflammatory cytokine from Tregs → IL-10
Fibrosis-promoting cytokine → TGF-β
Antibody blocking IL-4Rα in atopic dermatitis → dupilumab
Shared receptor chain lost in X-linked SCID → common γ chain (IL-2RG)