Harvey's Garden

Interleukin

2 min read

Key Pro-Inflammatory Cytokines

A useful mnemonic for the first six interleukins is “Hot T-Bone stEAk”:

  • IL-1 (Hot): Causes fever. Secreted by macrophages. Also promotes inflammation.
  • IL-2 (T): Stimulates T-cell growth and activation (both helper and cytotoxic T cells). Also activates B cells and NK cells. Aldesleukin is a recombinant form of IL-2 used in cancer therapy (e.g., RCC, melanoma).
  • IL-3 (Bone): Stimulates bone marrow stem cells (functions like GM-CSF).
  • IL-4 (E): Promotes IgE production and class switching. Induces differentiation of naïve T-helper cells to the Th2 subtype.
  • IL-5 (A): Promotes IgA production and stimulates the growth and differentiation of eosinophils.
  • IL-6 (aKute): Stimulates production of acute-phase reactants by the liver (e.g., CRP, fibrinogen). Also causes fever.

Other High-Yield Interleukins

  • IL-8 (CXCL8): Major chemotactic factor for neutrophils. Secreted by macrophages. Key for recruiting neutrophils to sites of inflammation.
    • “Clean up on aisle 8.” Neutrophils are recruited by IL-8 to clear infections.
  • IL-10: Primarily anti-inflammatory. Produced by Th2 cells and regulatory T cells (Tregs). Inhibits Th1 cell production and suppresses pro-inflammatory cytokine synthesis by macrophages.
    • TGF-β and IL-10 both attenuate the immune response.
  • IL-12: Induces differentiation of naïve T-helper cells into the Th1 subtype. Secreted by macrophages and dendritic cells. Activates NK cells.

T-Helper Cell Differentiation Summary

  • Th1 Pathway (Cell-mediated immunity):
    • Stimulated by: IL-12 (from APCs).
    • Th1 cells secrete: IFN-γ (activates macrophages) and IL-2 (stimulates T cells).
  • Th2 Pathway (Humoral/Allergic immunity):
    • Stimulated by: IL-4.
    • Th2 cells secrete: IL-4, IL-5, and IL-10.

Clinical Correlations

  • Anakinra: IL-1 receptor antagonist used for rheumatoid arthritis and other inflammatory conditions.
  • Tocilizumab: Monoclonal antibody against the IL-6 receptor, used for rheumatoid arthritis and giant cell arteritis.
  • Dupilumab: Monoclonal antibody against the IL-4 receptor alpha subunit, used for atopic dermatitis and allergic asthma.
  • Mepolizumab/Reslizumab/Benralizumab: Monoclonal antibodies targeting IL-5 or its receptor, used for severe eosinophilic asthma.

Graph View