title: Elevated sphingomyelinase and hypercytokinemia in hemophagocytic lymphohistiocytosis.
abstract: OBJECTIVE
  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.
  
  
  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 14C-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.
authors.affiliation: Department of Pediatrics, Akita University School of Medicine, Japan. tomy@med.akita-u.ac.jp
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Tamaki
authors.initials: T
authors.lastname: Abe
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sato
authors.forename: Kaori
authors.initials: K
authors.lastname: Miura
authors.forename: Ikuko
authors.initials: I
authors.lastname: Takahashi
authors.forename: Michihiro
authors.initials: M
authors.lastname: Yano
authors.forename: Arata
authors.initials: A
authors.lastname: Watanabe
authors.forename: Sinsaku
authors.initials: S
authors.lastname: Imashuku
authors.forename: Goro
authors.initials: G
authors.lastname: Takada
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D015616:Histiocytosis, Non-Langerhans-Cell / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D007223:Infant; D008297:Male; D013108:Sphingomyelin Phosphodiesterase / Q000097:blood*; D015854:Up-Regulation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D005047:Etoposide; D013108:Sphingomyelin Phosphodiesterase