Elevated sphingomyelinase and hypercytokinemia in hemophagocytic lymphohistiocytosis

Purpose: Ceramide generated from sphingomyelinase activation has been reported to play a role in cytokine-mediated events. Secretory sphingomyelinase (S-SMase), a product of the acid sphingomyelinase gene, has been found to be derived from many cell types and to exist in human serum. The purpose of the current study was to investigate the serum level of S-SMase. Patients and Methods: Three patients with hypercytokinemia caused by hemophagocytic lymphohistiocytosis (HLH) were studied. Serum samples were collected from the three patients with HLH, patients with a deficiency of acid sphingomyelinase, or type B Niemann-Pick disease, and normal controls. The S-SMase activities were determined using C-14-sphingomyelin as a substrate. Results: The serum S-SMase activities were increased 10- to 20-fold in the sera from the three patients with HLH (P < 0.0001). The high S-SMase activity was decreased to the normal level along with the clinical improvement of HLH. Conclusions: Increased release of S-SMase from cells into the circulation is observed in patients with active HLH. The authors suggest that S-SMase is related to the pathophysiology of hypercytokinemia.