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:
  • Chronic hepatitis B
  • Acute and chronic hepatitis C
  • Kaposi sarcoma
  • Adjuvant therapy for malignant melanoma
  • Renal cell carcinoma
  • Condyloma acuminatum
  • Hairy cell leukemia
  • Essential thrombocythemia
• Side Effects:
  • Flu-like symptoms (fever, chills)
  • Depression
  • Myopathy
  • Neutropenia
  • Interferon-induced autoimmunity
  • Gastrointestinal issues (nausea, vomiting, diarrhea)
  • Itchy skin

Interferon Beta (IFN-β)

• Therapeutic Use:
  • Multiple sclerosis

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:
  • Chronic granulomatous diseases (e.g., leprosy, leishmaniasis, toxoplasmosis)

Tumor Necrosis Factor Superfamily

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• 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
• 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:
  • Fibroblast proliferation
  • Stimulation of wound healing

Therapeutic Significance:

• TNF inhibitor etanercept can bind lymphotoxin-alpha