U01.02.021 Cytokines

Cytokines play critical roles in the immune system, mediating and regulating immunity, inflammation, and hematopoiesis. This guide organizes cytokines by their source, function, and clinical relevance, with memory aids and key points for easy recall.

Cytokines Secreted by Macrophages

Acute Phase Cytokines

Interleukin-1 (IL-1)
- Function:
  - Causes fever and acute inflammation.
  - Activates endothelium to express adhesion molecules.
  - Induces chemokine secretion for WBC recruitment.
- Clinical Note: Also called osteoclast-activating factor.
- Mnemonic: Hot T-bone stEAK:
  - IL-1 → Fever (Hot).
Interleukin-6 (IL-6)
- Function:
  - Causes fever.
  - Stimulates production of acute-phase proteins.
- Mnemonic: IL-6 stimulates aKute-phase protein production.
Tumor Necrosis Factor-α (TNF-α)
- Function:
  - Activates endothelium.
  - Causes WBC recruitment and vascular leak.
  - Maintains granulomas in tuberculosis.
  - Causes cachexia in malignancy.
- Clinical Note: IL-1, IL-6, and TNF-α mediate fever and sepsis.

Recruitment Cytokines

Interleukin-8 (IL-8)
- Function: Major chemotactic factor for neutrophils.
- Mnemonic: Clean up on aisle 8 → Neutrophils are recruited by IL-8 to clear infections.
Interleukin-12 (IL-12)
- Function:
  - Induces differentiation of T cells into Th1 cells.
  - Activates NK cells.

Cytokines Secreted by All T Cells

Interleukin-2 (IL-2)
- Function:
  - Stimulates growth of helper, cytotoxic, regulatory T cells, and NK cells.
Interleukin-3 (IL-3)
- Function:
  - Supports growth and differentiation of bone marrow stem cells.
  - Functions similarly to GM-CSF.

Cytokines Secreted by Th1 Cells

Interferon-γ (IFN-γ)
- Function:
  - Stimulates macrophages to kill phagocytosed pathogens.
  - Inhibits differentiation of Th2 cells.
  - Activates NK cells to kill virus-infected cells.
  - Enhances MHC expression and antigen presentation.
- Clinical Note: Crucial for granuloma formation in infections like TB.

Cytokines Secreted by Th2 Cells

Interleukin-4 (IL-4)
- Function:
  - Induces differentiation of T cells into Th2 cells.
  - Promotes growth of B cells.
  - Enhances class switching to IgE and IgG.
- Mnemonic: Ain’t too proud 2 BEG 4 help.
Interleukin-5 (IL-5)
- Function:
  - Promotes growth and differentiation of B cells.
  - Enhances class switching to IgA.
  - Stimulates eosinophil growth and differentiation.
Interleukin-10 (IL-10)
- Function:
  - Attenuates inflammatory response.
  - Decreases expression of MHC class II and Th1 cytokines.
  - Inhibits activated macrophages and dendritic cells.
- Clinical Note: Secreted by regulatory T cells.

Summary Table of Cytokines

Cytokine	Secreted By	Functions	Mnemonic/Note
IL-1	Macrophages	Fever, inflammation, chemokine secretion, osteoclast activation	Hot (fever) in Hot T-bone stEAK
IL-6	Macrophages	Fever, acute-phase protein production	Stimulates aKute phase proteins
TNF-α	Macrophages	Activates endothelium, WBC recruitment, vascular leak, cachexia	Fever, sepsis, TB granulomas
IL-8	Macrophages	Neutrophil recruitment	Clean up on aisle 8
IL-12	Macrophages	Differentiates T cells into Th1, activates NK cells	–
IL-2	All T cells	Growth of T cells and NK cells	–
IL-3	All T cells	Bone marrow stem cell differentiation	Like GM-CSF
IFN-γ	Th1 cells	Activates macrophages, inhibits Th2 cells, NK cell activation	Granuloma formation
IL-4	Th2 cells	Differentiation into Th2, B cell growth, IgE/IgG switching	2 BEG 4 help
IL-5	Th2 cells	B cell growth, IgA switching, eosinophil stimulation	–
IL-10	Th2/Regulatory T cells	Anti-inflammatory, inhibits Th1, dendritic cells, and macrophages	–

Points to Remember

IL-1, IL-6, and TNF-α are the primary mediators of fever and sepsis.
IL-8 specifically attracts neutrophils to infection sites.
IL-4 and IL-5 play critical roles in allergic responses and eosinophilic activation.
Interferon-γ is essential for macrophage activation and granuloma formation.
Anti-inflammatory cytokines like IL-10 regulate immune overactivation.

Quick Mnemonic Recap: Hot T-bone stEAK

IL-1: Fever (Hot).
IL-2: Stimulates T cells.
IL-3: Stimulates bone marrow.
IL-4: Stimulates IgE production.
IL-5: Stimulates IgA production.
IL-6: Stimulates aKute-phase protein production.

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