The immune system protects the body from invaders and disease, maintaining a delicate balance. Medical advances have led to specific therapies that target immune components to restore this balance, offering new possibilities for treating dysregulated immune responses.
Understanding Interferon Gamma
Interferon gamma (IFN-γ) is a signaling protein, or cytokine, central to the body’s immune defenses. It is primarily produced by activated T lymphocytes and natural killer (NK) cells.
IFN-γ mediates the fight against infections, including viruses, bacteria, and parasites. It activates macrophages, enhancing their ability to destroy infected cells and pathogens. This cytokine also influences T cell differentiation, orchestrating immune responses. IFN-γ contributes to immune surveillance against cancer by suppressing tumor development and promoting cancer cell death.
While beneficial for immune protection, excessive IFN-γ can contribute to inflammatory and autoimmune conditions. For example, in autoimmune diseases, IFN-γ can exacerbate tissue damage. Elevated IFN-γ levels are also detected in some infections, contributing to disease development.
Defining Anti-Interferon Gamma Antibodies
An anti-interferon gamma antibody is a specialized biologic medication designed to counteract the effects of interferon gamma. These antibodies are engineered to target and neutralize IFN-γ, often as monoclonal antibodies that recognize a single target molecule.
Their purpose is to block excessive IFN-γ activity, reducing inflammation and immune overactivity that can lead to tissue damage. This targeted approach modulates the immune system with greater precision than broader immunosuppressants.
How Anti-Interferon Gamma Antibodies Work
Anti-interferon gamma antibodies work by directly binding to IFN-γ molecules. This binding prevents IFN-γ from attaching to its specific receptors on cell surfaces, stopping its signaling cascade within cells.
Normally, IFN-γ binding triggers events inside the cell, including the activation of the Janus kinase (JAK)-STAT pathway. By blocking IFN-γ, the antibody stops this signaling pathway, preventing its downstream effects. This reduces pro-inflammatory cytokine production and suppresses macrophage and T cell activity, mitigating the harmful effects of uncontrolled IFN-γ.
Medical Applications of Anti-Interferon Gamma Antibodies
Anti-interferon gamma antibodies are used in conditions where IFN-γ overproduction contributes to disease. A primary example is Hemophagocytic Lymphohistiocytosis (HLH), a rare, severe hyperinflammatory disorder. In HLH, uncontrolled immune cell activation leads to an excessive release of inflammatory cytokines, with IFN-γ being a central driver.
The antibody emapalumab-lzsg (Gamifant) is approved for treating primary HLH and macrophage activation syndrome (MAS). By neutralizing IFN-γ, emapalumab reduces pathological effects and helps restore immune balance in these life-threatening conditions.
Safety and Administration
Anti-interferon gamma antibodies are typically administered intravenously. Dosage and frequency are adjusted based on patient response. Patients often take concomitant medications, such as dexamethasone.
Potential side effects exist. Common side effects include infections, high blood pressure, infusion-related reactions, and fever. Serious infections, such as sepsis, have been observed. Because these antibodies reduce IFN-γ activity, which fights infections, there is an increased risk of certain infections, including mycobacterial and fungal pathogens. Patients require close monitoring for signs of infection and other adverse reactions.