Levels of endothelial, neutrophil and platelet-specific factors in sickle cell anemia patients during hydroxyurea therapy

It has been shown that the clinical course of sickle cell (SS) patients can be ameliorated by administration of hydroxyurea (HU). Induction of hemoglo bin F (HbF) is thought to be the mechanism responsible for clinical improve ment in some patients. However, HU has a variable effect on HbF production and there exists no good correlation between the extent of HbF increase and clinical response. On the other hand, the degree of adherence of SS to vas cular endothelium and neutrophil counts correlate well with clinical severi ty. Being a cytotoxic drug, used in myeloproliferative diseases, HU may alt er proliferation among various cell lines. Moreover, HU has been reported t o reduce red blood cell (RBC) adhesion receptor expression in young SS indi viduals and induces changes in endothelial cells in vitro. It should be con ceived that in addition to its effects on HbF production, HU may change the clinical symptoms of SS patients by affecting the degree of adherence of d ifferent blood cells, by influencing the activity of endothelium as well as the activity of white blood cells (WBC) and platelets. To analyze whether several of the determinants of adhesion are modulated by HU treatment we st udied the levels of endothelial activity (soluble vascular adhesion molecul e-1, (sVCAM-1), interleukin-8 (IL-8), fibronectin, neutrophil activity (sL- selectin, sIL-6 receptor-alpha, myeloperoxidase) and platelet activity (von Willebrand factor) in relation to clinical symptoms, hematological data an d HbF levels in 8 SS patients before and during 5 months of HU therapy. Ste ady state sVCAM-1 levels are increased compared to normal controls and a si gnificant decrease is noted during HU treatment, suggesting a decrease in t he interactions between RBC and vascular endothelium. The IL-8 levels are c omparable to those in normal controls and remain unaffected by HU therapy. Intercurrent infection and crises reveal striking increases in IL-8 which a re accompanied by leukocytosis, but otherwise the IL-8 levels do not correl ate with hematological data. HU has no demonstrable effect on fibronectin o r soluble neutrophil adhesion molecules, but the levels of myeloperoxidase decrease significantly while WBC counts do not, implying a reduction in neu trophil activity which may help attenuate the propagation phase of a vasooc clusive crisis.