However, it should be noted that IFN-γ is not strictly necessary for the development of HLH, as is evident from HLH models in IFN-γ-deficient mice or the occurrence of HLH symptoms under IFN-γ blockade (21–24), as well as reports of HLH patients with an underlying IFN-γ-receptor deficiency (25). This evidence concerns the gene IFNG and hemophagocytic syndrome.