Soluble TWEAK is markedly elevated in hemophagocytic lymphohistiocytosis

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a newly identified monocyte derived cytokine, which has weak apoptosis inducing function against sensitive tumor cell lines in vitro. Also, TWEAK has been reported to have proangiogenic and proinflammatory activities in vivo. However, its functions in pathological situation remain to be elucidated. Here, we analyzed soluble TWEAK in serum of 24 patients with hernophagocytic lymphohistiocytosis (HLH) in combination with interferon-gamma (IFN-gamma) and killer-specific secretory protein of 37 kDa (Ksp37). Soluble TWEAK was not detected in serum of healthy individuals. Soluble TWEAK was markedly elevated in all six primary HLH patients and 12 of 18 secondary HLH patients. Serum IFI-gamma which is an only known mediator to stimulate TWEAK production in monocyte in vitro, was not elevated despite elevated serum TWEAK in three of six primary HLH patients, although IFI-gamma was markedly elevated in other cases. Ksp37 was only slightly increased in HLH patients. These results indicate that TWEAK may be involved in pathogenesis of HLH and is useful as a clinical marker.