Interferon Gamma
Type II interferon that activates macrophages and enhances immune function for chronic granulomatous disease and osteopetrosis.
Chemical Identity
| Property | Value |
|---|---|
| Molecular Weight | ~20-25 kDa (dimeric) |
| Amino Acids | 143 (monomer) |
| Gene | IFNG |
| Receptor | IFNGR1/IFNGR2 |
| Route | SC |
Structure
Interferon gamma (IFN-gamma) is the sole type II interferon, functioning as a non-covalent homodimer. Each monomer is 143 amino acids with two N-glycosylation sites. The active form is a dimer with antiparallel orientation of the two subunits.
Mechanism of Action
IFN-gamma binds IFNGR1/IFNGR2, activating JAK1/JAK2 and STAT1 signaling. This is the most potent activator of macrophages, enhancing microbicidal activity (reactive oxygen species, nitric oxide), antigen presentation (MHC class I and II), and inflammatory cytokine production. It also activates neutrophils and NK cells.
Clinical Applications
- Chronic granulomatous disease: Reducing infection frequency (Actimmune)
- Severe malignant osteopetrosis: Enhancing bone resorption
- Atopic dermatitis: Investigational
- Cancer immunotherapy: Under investigation
- Tuberculosis: Adjunctive therapy for MDR-TB
Pharmacokinetics
- Halflife: 3.8 hours (SC)
- Tmax: 7 hours (SC)
- Bioavailability: 89% (SC)
- Dosing: 50 mcg/m2 SC 3x/week (CGD)
- Route: SC
Safety and Side Effects
Flu-like symptoms (90%), fever, fatigue, headache, nausea, diarrhea, and hepatotoxicity. Neutropenia and thrombocytopenia with higher doses. Pre-medication with acetaminophen recommended.
References
- The International CGD Cooperative Study Group (1991). IFN-gamma for chronic granulomatous disease. New England Journal of Medicine, 324, 509-516.
- Gallin, J.I., et al. (1991). Long-term IFN-gamma for CGD. Annals of Internal Medicine, 115, 853-856.
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