Plasma Endothelin-1, Cytokine, and Prostaglandin E2Levels in Sickle Cell Disease and Acute Vaso-Occlusive Sickle Crisis

Abstract

The relative contributions of microvascular inflammation and vasomotor dysregulation to the development of acute vaso-occlusive crisis in sickle cell disease have been intensely studied. The present observational study was designed to examine the levels of circulating proinflammatory cytokines, anti-inflammatory cytokines, and vasoactive mediators during and after acute painful crisis. In symptomatic sickle cell patients, plasma levels of endothelin-1 and prostaglandin E2 were elevated during crises compared with healthy African-American controls. These levels had decreased, but not normalized, when patients were seen 1 to 3 weeks after discharge from hospital. Other mediators (tumor necrosis factor α [TNFα], interleukin-1β [IL-1β], IL-6, IL-8, and IL-10) were neither elevated in asymptomatic sickle cell disease nor in acute vaso-occlusive crisis. As a potent long-acting mediator of vasoconstriction and inflammation, endothelin-1 may play a key role in the cycle of ischemia and inflammation that initiates and sustains pain of crisis. The downregulatory effects of prostaglandin E2on immune cell function may contribute to the increased susceptibility to infection observed in patients with sickle cell disease.

Acute chest syndrome: sickle cell disease

“…sPLA 2 is normally present at low levels in plasma. It increases modestly in patients with pneumonia who do not have SCD, but to a comparatively lower level than in children who have SCD and ACS (95).…”

Biomarkers in sickle cell disease

“…, and serum levels of prostaglandin-E2(Graido- Gonzalez et al, 1998), CA 15-3(Symeonidis et al, 2006), soluble CD40 ligand(Lee et al, 2006), HSP-70(Adewoye et al, 2005), pentraxin 3(Nur et al, 2011a), ferritin(Brownell et al, 1986), angipoietin 1 and 2(Mohan et al, 2005), stromal derived factor 1), tumour necrosis factor-a(Cajado et al, 2011) and tumour necrosis factor receptor-1(Dworkis et al, 2011). Flowcytometry has also demonstrated increased expression of…”

Plasma endothelin‐1 levels in patients with complex regional pain syndrome

“…One potential biochemical marker for pain in patients with CRPS is the potent vasoconstrictive peptide, endothelin-1 (ET-1) (Yanagisawa et al, 1998). Multiple reports in animal (Raffa et al, 1996, Piovezan et al, 1998Davar et al, 1998;De-Melo et al, 1998;Jarvis et al, 2000;Gokin et al, 2001) and human studies (Dahlof et al, 1990;Graido-Gonzalez et al, 1998;Carducci et al, 2002) indicate that ET-1 is likely to be involved in the pathogenesis of pain. In humans, a rise in the plasma level of ET-1 was found in symptomatic sickle cell patients during and following sickle cell crises (Graido-Gonzalez European Journal of Pain 8 (2004) 533-538 www.…”