Interferon gamma (IFN-gamma) (IFN-gamma)

Interferon gamma (IFN-gamma) is a soluble cytokine that is the only member of the type II class of interferons [1]. It is primarily produced by natural killer (NK) cells and activated T lymphocytes in response to various stimuli, including interleukin-12 (IL-12) and interleukin-18 (IL-18) [2, 4]. IFN-gamma plays a central role in both innate and adaptive immunity by activating macrophages, enhancing their microbicidal activity, and inducing the expression of MHC class II molecules [1, 4]. Dysregulation of the IFN-gamma production pathway is implicated in several inflammatory and autoimmune diseases, most notably hemophagocytic lymphohistiocytosis (HLH), where excessive IFN-gamma levels drive a life-threatening hyperinflammatory state [3, 5]. Therapeutic targeting of this pathway involves direct neutralization of the cytokine using monoclonal antibodies like emapalumab, or indirect modulation through the inhibition of upstream cytokines or downstream Janus kinase (JAK) signaling [3]. While effective in controlling inflammation, inhibiting IFN-gamma can increase susceptibility to intracellular pathogens, such as mycobacteria [4].

Other names

IFN-gammaType II interferonImmune interferonIFNGInterferon gamma production pathway in leukocytes

Emapalumab is a monoclonal antibody that binds to and neutralizes soluble and membrane-bound IFN-gamma, preventing its interaction with the IFN-gamma receptor complex and inhibiting downstream JAK/STAT signaling [3]. Other drugs may target upstream activators like IL-12 or downstream signaling components like JAK1/2 to modulate the pathway's output [4].