CorpusHuman Anatomy
Lymphatic & ImmuneMolecule

Cytokines

Also known as: cytokine, interleukins, interferons, chemokines, tumour necrosis factor, tumor necrosis factor, TNF-alpha, IL-1, IL-2, IL-6, IL-8, IFN-gamma, colony-stimulating factors, TGF-beta

Small secreted proteins — interleukins, interferons, tumour necrosis factors, chemokines, colony-stimulating factors and TGF-β — that carry messages between immune cells and other tissues, controlling inflammation, cell growth, differentiation and migration.

Adaptive Immune Response

Overview

Cytokines are low-molecular-weight proteins (mostly 5–25 kDa) secreted transiently in response to stimuli and acting at very low (picomolar) concentrations on specific receptors. Most act locally — on the producing cell (autocrine) or on neighbours (paracrine) — but some, notably IL-1, IL-6 and TNF-α, act systemically (endocrine) to cause fever, the acute-phase response and, in excess, shock. They are pleiotropic (one cytokine, many effects), redundant (many cytokines, similar effects) and form networks of synergy and antagonism. Many signal through receptor-associated JAK kinases and STAT transcription factors; several interleukin receptors share the common γ chain (IL-2, -4, -7, -9, -15, -21), whose loss causes X-linked SCID.

Main families: interleukins (communication between leukocytes); interferons — type I (IFN-α/β) from virus-infected cells and plasmacytoid dendritic cells, which induce an antiviral state in neighbouring cells and upregulate MHC class I, and type II (IFN-γ) from Th1, CD8 and NK cells, the main macrophage-activating cytokine; the TNF family (TNF-α, lymphotoxin, RANKL, CD40L, FasL); chemokines, which direct cell migration (e.g. CXCL8/IL-8 for neutrophils, CCL2 for monocytes, CCL19/CCL21 acting on CCR7 for naive T cells and DCs, CXCL13 for B cells; CCR5 and CXCR4 are also HIV co-receptors); colony-stimulating factors (G-CSF, GM-CSF, M-CSF, IL-3) driving haematopoiesis; and TGF-β, which is broadly anti-inflammatory and pro-fibrotic.

Parts & subdivisions

  1. IL-1
    Macrophages (via the inflammasome): fever, acute-phase response, endothelial activation.
  2. IL-2
    Activated T cells: T-cell proliferation (autocrine), NK activation, Treg maintenance.
  3. IL-4, IL-5, IL-13
    Th2: IgE class switch and Th2 differentiation (IL-4), eosinophil production (IL-5), mucus and airway hyper-reactivity (IL-13).
  4. IL-6
    Macrophages, T cells, endothelium: fever, hepatic acute-phase proteins (CRP, fibrinogen, hepcidin), Th17 and plasma-cell differentiation.
  5. IL-8 (CXCL8)
    Macrophages and epithelium: neutrophil chemotaxis and activation.
  6. IL-10 and TGF-β
    Tregs, macrophages: anti-inflammatory, suppress Th1 and macrophage activation; TGF-β drives fibrosis and IgA class switching.
  7. IL-12
    Dendritic cells and macrophages: Th1 differentiation and NK activation.
  8. IL-17
    Th17: neutrophil recruitment, epithelial defence against bacteria and fungi.
  9. TNF-α
    Macrophages, T cells: vasodilatation and permeability, endothelial activation, fever, cachexia, granuloma maintenance; septic shock in excess.
  10. Interferons
    IFN-α/β: antiviral state, MHC I upregulation, NK activation. IFN-γ: macrophage activation, MHC II upregulation, Th1 polarisation.

Function

  • Coordinate innate and adaptive immune responses.
  • Induce inflammation, fever and the acute-phase response.
  • Direct leukocyte migration (chemokines).
  • Control lymphocyte activation, proliferation and differentiation into subsets.
  • Regulate haematopoiesis and terminate immune responses.

Clinical significance

Cytokine storm

Uncontrolled release of IL-6, IL-1, TNF-α and IFN-γ in sepsis, haemophagocytic lymphohistiocytosis, severe COVID-19 and after CAR-T or bispecific-antibody therapy (cytokine release syndrome) causes fever, capillary leak, hypotension and organ failure; anti-IL-6-receptor therapy (tocilizumab) is used.

Anti-cytokine biologics

Anti-TNF agents (infliximab, adalimumab, etanercept) treat rheumatoid arthritis, IBD, psoriasis and ankylosing spondylitis but can reactivate latent TB (screen first). Others: anakinra (IL-1 receptor antagonist) for autoinflammatory disease; tocilizumab (IL-6R); secukinumab (IL-17A); dupilumab (IL-4Rα); mepolizumab (IL-5).

Cytokines in chronic disease

IL-6-induced hepcidin blocks iron release, causing the anaemia of chronic disease; TNF-α contributes to cancer cachexia; interferon-β is used to treat relapsing multiple sclerosis.

Mnemonics

"Hot T-bone stEAK"

IL-1 hot (fever), IL-2 T cells, IL-3 bone marrow, IL-4 IgE, IL-5 IgA and eosinophils, IL-6 aKute-phase proteins. Bonus: IL-8 "clean up on aisle 8" — neutrophil recruitment; IL-10 calms things down; IL-12 makes Th1.

Compiled from standard anatomy and physiology references — see the Lymphatic & Immune System sources. For education only; not medical advice.