The Pathogenic Role of Interferons in the Hyperinflammatory Response on Adult-Onset Still’s Disease and Macrophage Activation Syndrome: Paving the Way towards New Therapeutic Targets

Abstract

Adult-onset Still’s disease (AOSD) is a systemic inflammatory disorder of unknown aetiology affecting young adults, which is burdened by life-threatening complications, mostly macrophage activation syndrome (MAS). Interferons (IFNs) are signalling molecules that mediate a variety of biological functions from defence against viral infections, to antitumor and immunomodulatory effects. These molecules have been classified into three major types: IFN I, IFN II, IFN III, presenting specific characteristics and functions. In this work, we reviewed the role of IFNs on AOSD and MAS, focusing on their pathogenic role in promoting the hyperinflammatory response and as new possible therapeutic targets. In fact, both preclinical and clinical observations suggested that these molecules could promote the hyperinflammatory response in MAS during AOSD. Furthermore, the positive results of inhibiting IFN-γ in primary hemophagocytic lymphohistiocytosis may provide a solid rationale to arrange further clinical studies, paving the way for reducing the high mortality rate in MAS during AOSD.