Leukocyte numbers correlate with plasma levels of granulocyte–macrophage colony-stimulating factor in sickle cell disease

Abstract

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.

Hydroxycarbamide reduces eosinophil adhesion and degranulation in sickle cell anaemia patients

“…Indeed, chemokines prime eosinophil ROS production (Chihara et al, 1998;Honda & Chihara, 1999). Other mediators able to induce eosinophil ROS production, such as PAF, IL5 and GM-CSF, are significantly elevated in SCA patients (Oh et al, 1997;Walter et al, 2006;Conran et al, 2007). The current study is the first to report higher eosinophil ROS production in SCA.…”

Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation

“…41 Factors associated with mast cell activation were also reduced in H/R-incited sickle mice following CP55,940 treatment. GM-CSF and white blood cell counts are elevated in SCA patients 26 and in sickle mice, and are both further increased by H/R incitement. 3 Our finding that CP55,940 decreased GM-CSF levels, leukocyte counts and also sickle red blood cells has important implications for improving vaso-occlusive crises and the accompanying pain.…”

“…GM-CSF plays a critical role in regulating leukocyte counts, which are often elevated in SCA. 26 We have previously reported leukocytosis in sickle mice and have shown that mast cells play a role in this process. 3 Treatment with CP55,940 significantly decreased white blood cell counts and sickle red blood cells, compared to the effect of vehicle, both under normoxia and following H/R incitement (Table 1).…”

The genetics of blood disorders: the hereditary hemoglobinopathies

“…A ativação dos monócitos, com a secreção de citocinas pró-inflamatórias (IL-1 e TNF-α), leva os leucócitos, em número constantemente elevado, a aderirem ao endotélio inflamado e a interagirem com as hemácias falcizadas [44][45][46][47][48][49] .…”