Over the last several years, it has become clear that inflammation plays a significant role in the clinical manifestations of sickle cell anemia, whether as a mediator of erythroid suppression or as a facilitator of thrombotic events. Determinations of the concentrations of the cytokine mediators of inflammation in serum or plasma of sickle cell patients have shown disparate results, particularly in patients not experiencing an acute crisis at the time. In studies of anemic patients with either AIDS or rheumatoid arthritis, determinations of bone marrow cytokine concentrations have provided unique correlations with clinical and laboratory parameters. We determined concentrations of IL-1, IL-6, TNF, and placental growth factor (PlGF) in bone marrow aspirates from 6 homozygous sickle cell (SS) patients who were not acutely ill and who were not receiving hydroxyurea, erythropoietin, or chronic transfusion, and compared them to specimens from 7 healthy controls. Concurrent plasma measurements were made when available. We also measured concentrations of soluble transferrin receptor (sTfR) and of marrow erythroid colony-forming units (CFU-E) as markers of erythropoietic activity. As expected, sTfR concentration, whether measured in marrow or plasma, was significantly higher in SS patients (p = .024). CFU-E concentration was not significantly different between the two groups. Although plasma IL-6 was significantly higher in SS patients, and plasma IL-1 significantly higher in controls, values measured were in the normal range. Bone marrow concentrations of IL-6 and IL-1 did not differ between the study groups. TNF was undetectable in all specimens, plasma or marrow. Other investigators have reported that elevated serum PlGF distinguishes SS patients from controls and correlates with disease activity. Plasma PlGF did not differ between SS patients and controls, but bone marrow PlGF concentrations were significantly higher in SS patients (p = .004). Since PlGF is a product of erythroid cells, the ratios of marrow PlGF to marrow CFU-E and sTfR were determined and also found to be significantly greater in SS patients (p = .016 and p = .024, respectively). None of the cytokines measured in SS patients correlated with clinical parameters. The bone marrow of stable SS patients exhibits an increased PlGF concentration not seen in circulating blood. This does not represent a phenomenon general to cytokines and does not reflect increased erythroid activity but rather an increase per erythropoietic unit. The role of PlGF in the clinical manifestations of sickle disease remains to be fully determined.
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