Harvey's Garden

Interferons and Tumor necrosis factor

3 min read

Tip

  • IFN-α & IFN-β (Type I)
    • Function: Induce an antiviral state in neighboring cells; ↑ MHC I.
  • IFN-γ (Type II)
    • Source: Th1 & NK cells.
    • Function: Activates macrophages & NK cells; ↑ MHC I & II; promotes Th1 differentiation; helps form granulomas.
  • TNF-α
    • Source: Macrophages.
    • Function: Mediates septic shock & cachexia; causes fever; maintains granulomas.
  • TNF-β (Lymphotoxin-alpha)
    • Source: Lymphocytes.
    • Function: Similar to TNF-α; supports lymphoid organogenesis.

Overview of Interferons

Type I Interferons

Interferon Alpha (IFN-α)

  • Mainly Secreted By:
    • Virus-infected cells and malignant cells
    • Fibroblasts (interferon-β)
  • Function:
    • Acts as the first line of defense against all viral infections
    • Inhibits viral protein synthesis by activating ribonuclease L, leading to the degradation of cellular and viral mRNA
    • Promotes the expression of MHC class I molecules, aiding in the recognition of virus-infected cells and activation of NK cells and cytotoxic T cells
    • Inhibits megakaryocyte stem cell differentiation and proliferation
  • Therapeutic Use:
  • Side Effects:
    • Flu-like symptoms (fever, chills)
    • Depression
    • Myopathy
    • Neutropenia
    • Interferon-induced autoimmunity
    • Gastrointestinal issues (nausea, vomiting, diarrhea)
    • Itchy skin

Interferon Beta (IFN-β)

Type II Interferons

Interferon Gamma (IFN-γ)

  • Mainly Secreted By:
    • Th1 and NK cells (when stimulated by IL-12 from macrophages or antigen contact)
  • Function:
    • Activates macrophages to increase phagocytosis (positive reinforcement) and NK cells to eliminate virus-infected target cells
    • Synergistic effect with tumor necrosis factor in stimulating macrophages to form granulomas, crucial against mycobacterial infections
    • Suppresses a Th2 response (negative feedback)
    • Promotes the expression of MHC class II molecules and antigen presentation in every cell
    • Stimulates antigen class switching to IgG3
  • Therapeutic Use:

Tumor Necrosis Factor Superfamily

  • Pro-inflammatory cytokines secreted by leukocytes in response to inflammation and/or infection
  • Their signaling pathways regulate inflammation, apoptosis, and cellular proliferation and differentiation
  • There are over 20 tumor necrosis factors, with cachectin and lymphotoxin-alpha being the most important

Cachectin (Tumor Necrosis Factor, formerly TNF-α)

Secreted by:

  • Activated macrophages

Functions:

  • Pyrogenic
  • Cytotoxic and inhibits carcinogenesis of certain tumors
  • Mediates septic shock by activating the endothelium, leading to:
    • Vascular leakage
    • Recruitment of white blood cells
  • Causes malignant cachexia
    • Its role in cachexia is explained by its influence on the hypothalamus, leading to appetite suppression. It also increases basal metabolic rate.
  • Maintains granulomas, which are critical for defense against mycobacterial infections

Therapeutic Significance:

  • TNF inhibitors like infliximab are used to treat refractory chronic inflammatory systemic diseases (e.g., Crohn disease)

Lymphotoxin-alpha (formerly TNF-β)

Secreted by:

  • Activated lymphocytes

Functions:

  • Cytotoxic, leading to inhibition of carcinogenesis
  • Promotes colony stimulating factor synthesis, which leads to:

Therapeutic Significance:

  • TNF inhibitor etanercept can bind lymphotoxin-alpha

Graph View

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