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IFNγ is a key cytokine in the immune system1

Interferon gamma (IFNγ) is the only type II interferon and plays an important role in cell communication during immune responses.1-5 During innate immune responses, IFNγ helps eliminate intracellular pathogens by activating macrophages and natural killer (NK) cells.1,3 During adaptive immune responses, IFNγ is responsible for both the differentiation and overproliferation of activated T cells.6,7

IFNγ can be produced by CD4+ T-helper type 1 (T1) cells, activated CD8+ T cells, NK cells, NK T cells, B cells, and antigen-presenting cells (APCs).1,7

IFNγ is a driver of hyperinflammation

Preclinical data suggest that the cytokine IFNγ plays a central and upstream role in the pathogenesis of primary hemophagocytic lymphohistiocytosis (HLH). Massive overexpression of IFNγ leads directly to downstream hypercytokinemia and hyperinflammation.2,8,9

While downstream cytokines—including IL-10, IL-12, IL-18, anti-TNF, anti–M-CSF, and anti–GM-CSF—likely impact inflammatory symptoms, animal studies attempting to suppress such cytokines have not shown any positive impact.2

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Genetic mutations disrupt immune function

In healthy individuals, APCs are recognized by cytotoxic CD8+ T cells, which bind to them to release perforin and granzymes into the immunological synapse space. Perforin creates pores in the target cell's plasma membrane, allowing the cytotoxic granzymes to enter and initiate lysis. In primary HLH, genetic mutations prevent perforin pore formation needed for cell lysis.10-12

See how IFNγ unleashes the storm

Click through to see how IFNγ drives the uncontrolled release of cytokines, which result in the rapidly progressive and life-threatening symptoms of untreated primary HLH.

IFNγ drives the uncontrolled release of cytokines, which result in the rapidly progressive and life-threatening symptoms of primary HLH.

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IFNγ Guide