CSF2 and Splenomegaly: Although the current study did not specify which cytokine played a major role in the pathogenesis of HLH, GM-CSF is assumed to be the primary pathogenic cytokine, as the huSGM3 mice shared many of the findings observed in a mouse HLH model driven by GM-CSF overexpression, such as short survival, splenomegaly, lymphadenopathy, thymic atrophy, and multiple abnormalities in blood cell populations including progressing anemia (27).