Interferons

Snapshot

• A 50-year-old man with a history of HIV presents to his infectious disease clinic for a rash. He reports that he stopped taking his anti-retroviral medication about 2 months ago due to gastrointestinal upset with each dose. He reports feeling well overall but reports developing a painless rash on his legs. Yesterday, he had night sweats and a low-grade fever.  On physical exam, there are scattered violaceous papules and plaques on his bilateral lower extremities. Laboratory studies reveal a CD4+ count of < 200/uL. A skin biopsy is taken, and the patient is restarted on antiretrovirals and started on interferon therapy. (Kaposi sarcoma)

Overview

• Drugs
  • interferon-α
  • interferon-β
  • interferon-γ
• Mechanism of action
  • interferons are part of the innate host defense against viruses 
    • they are glycoproteins that are naturally made by virus-infected cells to fight the infection
    • interferon upregulates MHC expression
  • interferon-α and interferon-β
    • downregulates protein synthesis to prevent viral replication
  • interferon-γ
    • secreted by NK cells and T cells, activating macrophages
    • activates NK cells to also eliminate virus-infected cells
• Clinical use
  • viral infections, tumors, malignancies, and other conditions
  • interferon-α
    • hepatitis B
    • hepatitis C
    • Kaposi sarcoma
    • condyloma acuminatum
    • hairy cell leukemia
    • renal cell carcinoma
    • malignant melanoma
    • follicular lymphoma
  • interferon-β
    • multiple sclerosis
  • interferon-γ
    • chronic granulomatous disease
    • osteopetrosis
• Adverse effects
  • flu-like symptoms
  • neutropenia
  • depression
  • myopathy
  • focal segmental glomerulosclerosis (nephrotic syndrome)