TNF and Splenomegaly: ,3-5,9 Clinical symptoms and laboratory investigations which are part of diagnostic criteria are directly associated with the pathophysiology of HLH: aggregation of lymphocytes and macrophages causing splenomegaly, elevated interleukin 1 resulting in fever, high tumor necrosis factor yielding hypertriglyceridemia, inflammatory macrophage scavenging causing elevated ferritin, and elevated levels of interferon-gamma and tumor necrosis factor leading to cytopenia.1