Increased cytokine levels and abnormal response of myeloid progenitor cells to granulocyte colony-stimulating factor in a case of severe congenital neutropenia. In vitro effects of stem cell factor.
OBJECTIVE
The cytokine levels and the in vitro granulopoiesis were studied to evaluate the mechanism of impaired granulopoiesis in severe congenital neutropenia (SCN).


METHODS
The patient was a 5-year-old boy with SCN. We assayed the colony-stimulating activity (CSA) produced by peripheral blood (PB) cells from the patient. The plasma levels of cytokines were measured using enzyme immunoassay. These included granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-6, and tumor necrosis factor-alpha. The effects of IL-3 and stem cell factor (SCF) on the proliferation of granulocyte-macrophage colony-forming cells (GM-CFCs) were studied.


RESULTS
CSA produced by PB cells from the patient was almost the same as in the healthy control. The level of endogenous G-CSF was elevated to 334 pg/ml, and GM-CSF, IL-2, IL-3, and IL-6 were slightly elevated. The numbers of GM-CFCs were markedly depressed in the presence of G-CSF alone and showed no increment on additional stimulation by IL-3. SCF in combination with G-CSF significantly augmented the proliferation of GM-CFCs.


CONCLUSIONS
These findings suggest that some cytokines including G-CSF may be elevated in SCN patients and that CSF may play an important role in the pathogenesis of SCN.
Shitara
T
T
Department of Pediatrics, Gunma University School of Medicine, Maebashi City, Japan.
Ijima
H
H
Yugami
S
S
Sotomatu
M
M
Kuroume
T
T
D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D016207:Cytokines / Q000097:blood*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009503:Neutropenia / Q000151:congenital* / Q000209:etiology; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor
D003115:Colony-Stimulating Factors; D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor