PLASMA ENDOTHELIN-1, CYTOKINE, AND PROSTAGLANDIN E-2 LEVELS IN SICKLE-CELL DISEASE AND ACUTE VASOOCCLUSIVE SICKLE CRISIS

The relative contributions of microvascular inflammation and vasomotor dysregulation to the development of acute vaso-occlusive crisis in si ckle cell disease have been intensely studied. The present observation al study was designed to examine the levels of circulating proinflamma tory cytokines, anti-inflammatory cytokines, and vasoactive mediators during and after acute painful crisis, In symptomatic sickle cell pati ents, plasma levels of endothelin-l and prostaglandin E-2 were elevate d during crises compared with healthy African-American controls. These levels had decreased, but not normalized, when patients were seen 1 t o 3 weeks after discharge from hospital. Other mediators (tumor necros is factor alpha [TNF alpha], interleukin-1 beta [IL-1 beta], IL-6, IL- 8, and IL-10) were neither elevated in asymptomatic sickle cell diseas e nor in acute vaso-occlusive crisis. As a potent long-acting mediator of vasoconstriction and inflammation, endothelin-l may play a key rol e in the cycle of ischemia and inflammation that initiates and sustain s pain of crisis. The downregulatory effects of prostaglandin E-2 On i mmune cell function may contribute to the increased susceptibility to infection observed in patients with sickle cell disease. (C) 1998 by T he American Society of Hematology.