Anti-inflammatory properties of pro-inflammatory interferon-gamma

Production of interferon-gamma (IFNgamma) in response to infection is a hallmark of innate and adaptive immunity. In addition to the pivotal role of IFNgamma in host defense, its excessive release has been associated with the pathogenesis of chronic inflammatory and autoimmune diseases. In fact, knockout models reveal that IFNgamma plays a key role in mediating a number of pathological processes related to chronic immune activation. On the other hand, evidence has been accumulated in recent years that supports the concept of a dual role of IFNgamma in inflammation. Here, we review anti-inflammatory aspects of IFNgamma in the regulatory network of cytokine biology. These include induction of anti-inflammatory molecules such as interleukin (IL)-1 receptor antagonist (IL-1Ra) and IL-18 binding protein (IL-18BP), modulation of pro-inflammatory cytokine production, activation of apoptosis, and interference with the signal transduction machinery by induction of suppressors of cytokine signaling (SOCS).