Leukocyte numbers correlate with plasma levels of granulocyte-macrophage colony-stimulating factor in sickle cell disease.
Despite a clear role for leukocytes in modulating the pathophysiology of sickle cell disease (SCD), the mechanism by which leukocyte numbers are increased in this disorder remains unclear. Hypothesizing that the chronic inflammatory state, elicited by adhesive interactions involving various cell types, might underlie leukocytosis, we measured plasma levels of proinflammatory or myeloid cytokines that play a role in leukocytosis and examined their correlations with leukocyte numbers in patients with SCD. Our studies found that, although plasma levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3, and macrophage colony-stimulating factor are elevated in steady-state patients with SCD, only plasma GM-CSF levels are positively correlated with the numbers of total leukocytes, neutrophils, monocytes, and eosinophils, regardless of whether they received hydroxyurea. GM-CSF levels were significantly decreased in patients on hydroxyurea therapy. These data suggest a role of GM-CSF in leukocytosis of SCD. In contrast, plasma levels of granulocyte colony-stimulating factor, a major cytokine that induces leukocytosis due to bacterial infection, were lower than those of control subjects. These results indicate that elevated GM-CSF levels may contribute, at least in part, to high leukocyte numbers in SCD. As plasma GM-CSF levels were decreased in patients on hydroxyurea therapy, hydroxyurea may decrease leukocyte numbers by reducing circulating GM-CSF levels.
Conran
Nicola
N
Hematology and Hemotherapy Center, University of Campinas, UNICAMP-SP, Campinas, Brazil.
Saad
Sara T O
ST
Costa
Fernando F
FF
Ikuta
Tohru
T
D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000188:drug therapy; D016022:Case-Control Studies; D002648:Child; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007377:Interleukin-3 / Q000097:blood; D007958:Leukocyte Count; D007964:Leukocytosis / Q000097:blood*; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism
D007377:Interleukin-3; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006918:Hydroxyurea