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)