interferongamma

Interferon-gamma (IFN-γ) is a type II interferon, a cytokine central to both innate and adaptive immunity. It is primarily produced by natural killer (NK) cells and T lymphocytes, especially Th1 cells and cytotoxic CD4+ and CD8+ T cells, in response to intracellular pathogens or interleukin-12 stimulation. The IFNG gene, which encodes IFN-γ, is located on chromosome 12 in humans.

Mechanism of action and signaling occur via the IFN-γ receptor (IFNGR1 and IFNGR2) on most cell types. Binding activates JAK1 and JAK2 kinases, leading to phosphorylation and dimerization of STAT1, which translocates to the nucleus to drive transcription of IFN-γ–stimulated genes. This results in enhanced antigen presentation, particularly through upregulation of MHC class II molecules (via CIITA), increased macrophage activation, and antimicrobial activities such as inducible nitric oxide synthase (iNOS). IFN-γ also promotes Th1-biased immune responses and helps control intracellular pathogens, including certain bacteria and viruses.

Clinical relevance and diagnostic use are notable. Defects in IFN-γ signaling cause susceptibility to disseminated mycobacterial and fungal infections, a condition known as Mendelian susceptibility to mycobacterial disease (MSMD). IFN-γ is used diagnostically in interferon gamma release assays (IGRAs) to detect latent tuberculosis infection by measuring IFN-γ release from T cells in response to TB antigens.

Therapeutic applications include recombinant human IFN-γ (IFN-γ-1b), which has been developed and approved in some countries for conditions such as chronic granulomatous disease and other severe infections to boost macrophage function.

Safety considerations include flu-like symptoms, injection-site reactions, and potential autoimmune effects with long-term use.