Interferon-gamma (IFN-γ) plays a key role in the pathophysiology of 
hemophagocytic lymphohistiocytosis (HLH), and available evidence also points to 
a role in other conditions, including aplastic anemia (AA) and graft failure 
following allogeneic hematopoietic stem cell transplantation. Recently, the 
therapeutic potential of IFN-γ inhibition has been documented; emapalumab, an 
anti-IFN-γ monoclonal antibody, has been approved in the United States for 
treatment of primary HLH that is refractory, recurrent or progressive, or in 
patients with intolerance to conventional therapy. Moreover, ruxolitinib, an 
inhibitor of JAK/STAT intracellular signaling, is currently being investigated 
for treating HLH. In AA, IFN-γ inhibits hematopoiesis by disrupting the 
interaction between thrombopoietin and its receptor, c-MPL. Eltrombopag, a 
small-molecule agonist of c-MPL, acts at a different binding site to IFN-γ and 
is thus able to circumvent its inhibitory effects. Ongoing trials will elucidate 
the role of IFN-γ neutralization in secondary HLH and future studies could 
explore this strategy in controlling hyperinflammation due to CAR T cells.