Calming the storm in HLH

Abstract

In this issue of Blood, Albeituni et al demonstrate the pleiotropic immunomodulatory effects by which the Janus kinase (JAK) inhibitor ruxolitinib ameliorates hypercytokinemia and organ injury in 2 distinct murine models of hemophagocytic lymphohistiocytosis (HLH).1 By demonstrating both interferon-γ (IFN-γ)-dependent and IFN-γ-independent effects, the authors provide compelling preclinical data supporting the potential superiority of ruxolitinib when compared with IFN-γ inhibition alone. In doing so, the authors also identify a previously underrecognized role of neutrophil cytotoxicity in the pathobiology of HLH-induced multiorgan dysfunction.