ABSTRACT
Acute painful episodes represent the most frequent and prominent manifestation of sickle cell disease. Vasospasm and inflammation might play important roles in the pathophysiology of pain crisis. Endothelin-1, which is a vasoconstrictor peptide released from damage of endothelial cells in homozygous sickle cell disease [SS disease], may play a role during crisis. Inflammatory events as cytokine production and adhesion molecular expression may also occur. The present study was designed to investigate plasma levels of endothelin-1 and interlukin-1Beta [proinflammatory cytokine] in asymptomatic sickle cell disease and during pain crisis. The study included 20 children with homozygous sickle cell anemia admitted for painful crisis. Fifteen age and sex matched children were included as a control group. Blood samples were collected from controls and from patients on the first day of crisis and then 4 weeks later [steady state]. Plasma levels of endothelin-1 [ET-1] and interlukin-1Beta in patients' and control samples were determined using commercially available enzyme-Iinked immunosorbent assay [ELISA]. The results showed that plasma ET-1 levels were significantly elevated relative to healthy controls [1.5235 +/- 0.939 pg/ml] in both patients in acute pain crisis [81.9 +/- 44.4 pg/ml] and those after crisis [15.97 +/- 6.96 pg/ml]. Meanwhile, plasma interlukin-1B [IL-1B] levels were not significantly different between normal controls [148.75 +/- 39.31 pg/ml] and patients during painful crisis [139.8 +/- 44.3 pg/ml] or after crisis [144.8 +/- 17.4 pg/ml]
Conclusion: Endothelin-1 could contribute to both the prolonged vasospasm and to inflammation in acute painful sickle cell crisis and that endothelin antagonist strategies might have utility in the treatment of this complex disorder. A direct role for IL-1Beta in the pathogenesis of vascular occlusion in sickle cell disease could not be demonstrated, but an indirect role was not excluded