Learning Objective

Describe the mechanism, immunologic role, clinical uses, and adverse effects of Type I interferons (IFN-α and IFN-β), and explain how they contribute to antiviral and antitumor immunity.

Type I interferons, including IFN-α and IFN-β, are key components of the innate immune response against viral infections and certain malignancies.

Mechanism of Action

Type I interferons are produced by virus-infected cells and act in a paracrine manner on nearby cells to prepare them for viral invasion:

1. ↓ Viral replication
   • Inhibit viral and host protein synthesis to prevent viral replication.
2. ↑ MHC I expression
   • Enhances recognition and killing of infected cells by CD8⁺ cytotoxic T cells.
3. Activates antiviral state
   • Induces RNase L and protein kinase R (PKR), which degrade viral mRNA and inhibit viral protein synthesis.
4. Promotes antitumor immunity
   • Enhances NK cell activity
   • Increases tumor antigen presentation

Clinical Uses of Type I Interferons

• Chronic HBV infection
• Chronic HCV infection (rare now due to better drugs)
• Kaposi sarcoma
• Hairy cell leukemia
• Condyloma acuminatum (HPV)
• Malignant melanoma

IFN-β is used for:

• Multiple sclerosis (MS): Reduces inflammatory T-cell movement across the blood–brain barrier

Adverse Effects

• Flu-like symptoms (fever, malaise, myalgias)
• Depression (important exam point)
• Neutropenia
• Myopathy
• Interferon-induced autoimmunity
  • eg, thyroiditis, lupus-like syndrome

Activity