1EKU, 1FG9, 1FYH, 1HIG, 3BES345815978ENSG00000111537ENSMUSG00000055170P01579P01580NM_000619NM_008337NP_000610NP_032363Interferon gamma (IFNG or IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons.

[7] or tuberculin-sensitized mouse peritoneal lymphocytes[8] challenged with Mantoux test (PPD); the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus.

Those reports also contained the basic observation underlying the now widely employed interferon gamma release assay used to test for tuberculosis.

[15] Type II IFN has played a role in the development of cancer immunotherapy treatments due to its ability to prevent tumor growth.

[13] IFNG, or type II interferon, is a cytokine that is critical for innate and adaptive immunity against viral, some bacterial and protozoan infections.

IFNG is an important activator of macrophages and inducer of major histocompatibility complex class II molecule expression.

Activation of the JAK-STAT pathway induces upregulation of interferon-stimulated genes (ISGs), including MHC II.

[citation needed] The biological significance of heparan sulfates interaction with IFNG is unclear; however, binding of the D1 cluster to HS may protect it from proteolytic cleavage.

The proteins expressed by type II IFN-mediated signaling are primarily involved in promoting inflammatory immune responses and regulating other cell-mediated immune responses, such as apoptosis, intracellular IgG trafficking, cytokine signaling and production, hematopoiesis, and cell proliferation and differentiation.

They then initiate transcription by binding to gamma interferon activation site (GAS) elements,[12] which are located in the promoter region of Interferon-stimulated genes (ISGs) that express for antiviral effector proteins, as well as positive and negative regulators of type II IFN signaling pathways.

PI3K leads to the activation of protein kinase C delta type (PKC-δ) which phosphorylates the amino acid serine in STAT1 transcription factors.

IFNG suppresses osteoclast formation by rapidly degrading the RANK adaptor protein TRAF6 in the RANK-RANKL signaling pathway, which otherwise stimulates the production of NF-κB.

Further activation of macrophages causes a cycle of further killing of intracellular bacteria, and further presentation of antigens to Th1 helper cells with further release of IFNG.

[citation needed] Uterine natural killer cells (NKs) secrete high levels of chemoattractants, such as IFNG in mice.

IFNG dilates and thins the walls of maternal spiral arteries to enhance blood flow to the implantation site.

[39][40] Interferon gamma 1b is approved by the U.S. Food and Drug Administration to treat chronic granulomatous disease[41] (CGD) and osteopetrosis.

[42] The mechanism by which IFNG benefits CGD is via enhancing the efficacy of neutrophils against catalase-positive bacteria by correcting patients' oxidative metabolism.

In 2002, the manufacturer InterMune issued a press release saying that phase III data demonstrated survival benefit in IPF and reduced mortality by 70% in patients with mild to moderate disease.

InterMune's chief executive, Scott Harkonen, was accused of manipulating the trial data, was convicted in 2009 of wire fraud, and was sentenced to fines and community service.

[45] Preliminary research on the role of IFNG in treating Friedreich's ataxia (FA) conducted by Children's Hospital of Philadelphia has found no beneficial effects in short-term (< 6-months) treatment.

[49] Although not officially approved, Interferon gamma has also been shown to be effective in treating patients with moderate to severe atopic dermatitis.

Thus, promoting the upregulation of type II IFN has been proven to be a crucial part in creating effective cancer immunotherapy treatments.

On the contrary, it was stressed: "Interferon-γ secreted by CD8-positive lymphocytes upregulates PD-L1 on ovarian cancer cells and promotes tumour growth.

[57] The importance of type II IFN in cancer immunotherapy has been acknowledged; current research is studying the effects of type II IFN on cancer, both as a solo form of treatment and as a form of treatment to be administered alongside other anticancer drugs.

But type II IFN has not been approved by the Food and Drug Administration (FDA) to treat cancer, except for malignant osteoporosis.

This is most likely due to the fact that while type II IFN is involved in antitumor immunity, some of its functions may enhance the progression of a cancer.

[60][61] Interferon gamma has been shown to be a crucial player in the immune response against some intracellular pathogens, including that of Chagas disease.

In human epithelial cells, IFNG upregulates expression of indoleamine 2,3-dioxygenase, which in turn depletes tryptophan in hosts and impedes chlamydia's reproduction.

[71] In both the human and rodent systems, chlamydia has evolved mechanisms to circumvent the negative effects of host cell behavior.