Cytokine gene expression in the marrow stromal cells of patients with giant cell arteritis.
OBJECTIVE
Anemia of chronic disease is a common feature of giant cell arteritis (GCA). It has been shown that constitutive hematopoiesis is regulated in the bone marrow microenvironment by direct cell-to-cell contact between hematopoietic progenitor cells and marrow stromal cells. Since cytokines are of crucial significance in this process, we decided to examine the role of stem cell factor (SCF), granulocyte macrophage colony stimulating factor (GM-CSF), interleukin 3 (IL-3), granulocyte colony stimulating factor (G-CSF), and interleukin 1 alpha (IL-1 alpha), known for their stimulatory effects on in vitro hematopoiesis; and transforming growth factor beta (TGF beta), interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF-alpha), known for their inhibitory effect, in the anemia of GCA.


METHODS
The expression of these cytokines was examined in the marrow stromal cells from 6 GCA patients with anemia of chronic disease and in 6 healthy individuals by the reverse transcription mediated polymerase chain reaction (RT-PCR).


RESULTS
Consistent constitutive gene expression was detected in the marrow stromal cells of all control samples for SCF, GM-CSF, IL-1 alpha, TGF beta and TNF-alpha, while only 2/6 expressed IFN gamma. None of the controls expressed either IL-3 or G-CSF. In all GCA patients SCF, TGF beta and TNF-alpha were expressed, but the level of expression was reduced compared to the control group. IL-1 alpha was expressed in 3/6 patients, and IFN gamma in 2/6. More importantly, GM-CSF expression was not detected in any patient, in marked contrast with the controls.


CONCLUSIONS
The combination of the defective expression of SCF and GM-CSF, cytokines with a known stimulatory effect on in vitro hematopoiesis, may contribute to the pathogenesis of anemia in GCA.
Orphanos
V
V
Division of Hematology, Medical School, University of Patras, Greece.
Andonopoulos
A P
AP
Kourakli
A
A
Zoumbos
N C
NC
D000740:Anemia / Q000209:etiology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D013700:Giant Cell Arteritis / Q000150:complications / Q000378:metabolism*; D006801:Humans; D008297:Male; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism
D016207:Cytokines; D017931:DNA Primers; D018076:DNA, Complementary; D012313:RNA