Elevated sphingomyelinase and hypercytokinemia in hemophagocytic lymphohistiocytosis.
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.
Takahashi
Tsutomu
T
Department of Pediatrics, Akita University School of Medicine, Japan. tomy@med.akita-u.ac.jp
Abe
Tamaki
T
Sato
Takayuki
T
Miura
Kaori
K
Takahashi
Ikuko
I
Yano
Michihiro
M
Watanabe
Arata
A
Imashuku
Sinsaku
S
Takada
Goro
G
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
D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D005047:Etoposide; D013108:Sphingomyelin Phosphodiesterase