Roles of specific cytokines in bone remodeling and hematopoiesis in Gaucher disease.
BACKGROUND
Gaucher disease type 1 and type 3 are characterized by bone disease and hematological symptoms. It is known that monocyte/macrophage lineage is activated in Gaucher disease, and accordingly certain cytokines are elevated in blood. The aim of the present study was to explore the possible relationships between cytokines and bone remodeling and hematological abnormalities in this disease.


METHODS
The concentrations of seven cytokines and two related proteins were measured in patients with Gaucher disease type 1 and type 3 (n= 8; age range, 2-50 years) who had received enzyme replacement therapy.


RESULTS
Concentrations of interleukin-18 and transforming growth factor-beta1 were elevated in patients of all clinical types. Elevation of these cytokines in Gaucher disease has not been previously reported. Analysis of correlation among cytokines and bone-turnover markers showed that interleukin-18 concentration was correlated with each of two bone formation markers of bone-specific alkaline phosphatase activity and osteocalcin concentration, whereas macrophage colony-stimulating factor concentration correlated with the bone absorption marker of N-telopeptide to helix in urine. Concentrations of macrophage colony-stimulating factor and tumor necrosis factor-alpha were inversely correlated with hemoglobin concentration.


CONCLUSIONS
Interleukin-18 and monocyte macrophage colony-stimulating factor are cytokines mainly involved in the mechanism of bone disease, while macrophage colony-stimulating factor and tumor necrosis factor-alpha may play a role in the development of hematological abnormalities in Gaucher disease.
Yoshino
Makoto
M
Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan. yoshino@med.kurume-u.ac.jp
Watanabe
Yoriko
Y
Tokunaga
Yasuyuki
Y
Harada
Eimiei
E
Fujii
Chieko
C
Numata
Sanae
S
Harada
Masaru
M
Tajima
Asako
A
Ida
Hiroyuki
H
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D005260:Female; D005776:Gaucher Disease / Q000097:blood / Q000503:physiopathology*; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D020382:Interleukin-18 / Q000097:blood; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D053773:Transforming Growth Factor beta1 / Q000097:blood
D015415:Biomarkers; D016207:Cytokines; D020382:Interleukin-18; D053773:Transforming Growth Factor beta1; D015675:Osteocalcin; D016173:Macrophage Colony-Stimulating Factor; D000469:Alkaline Phosphatase