The role of cytokines in sickle cell disease

Makis, Alexandres Chr.; Hatzimichael, Eleftheria; Bourantas, K. L.

doi:10.1007/s002770000173

Cited by 98 publications

(80 citation statements)

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“…Patients with SCD have a chronic low-grade pro-inflammatory state, even at a steady state condition [7,20]. They have elevated levels of circulating cytokines and vascular adhesion molecules (e.g., VCAM-1), hypercoagulable state and endothelial dysfunction, which all can contribute to vascular inflammation [36][37][38][39][40][41][42][43][44][45][46]. Sickle red cells, and in particular sickle reticulocytes, express a number of adhesion receptors that can mediate adherence to vascular endothelial cells and consequently contribute to endothelial dysfunction [47].…”

Section: Coronary Artery Ectasia In Sickle Cell Diseasementioning

confidence: 99%

Coronary Artery Ectasia in Atherosclerotic Coronary Artery Disease, Inflammatory Disorders, and Sickle Cell Disease

Dahhan

2015

Cardiovascular Therapeutics

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SUMMARYCoronary artery ectasia (CAE) or aneurysm is usually defined as dilation ≥1.5-fold the normal vessel diameter. It has an incidence of 1.4-5.3% and is associated with a wide variety of etiologies-mainly congenital, atherosclerotic, and inflammatory ones. CAE is very common in sickle cell disease, and possibly sickle cell trait, with an incidence of 17.7%. It is likely related to the inflammatory process associated with hemoglobin S. Prognosis depends mainly on the underlying etiology. Atherosclerotic CAE does not carry additional risks compared to atherosclerotic coronary artery disease (ACAD) without ectasia. However, isolated CAE in the absence of ACAD carries an increased risk of myocardial infarction (MI) due to vasospasm, slower coronary blood flow, and thrombosis, typically within the dilated segments. Due to lack of studies and guidelines, management recommendations are based on personal experiences. Therapy should be tailored to each individual case after assessment of severity, history of complications, underlying etiology, and comorbidities. Treatment of underlying condition and avoidance of exacerbating factors are essential. Medical therapy in general may include antiplatelets, b-blockers, angiotensin-converting enzyme inhibitors statins, and dihydropyridine calcium channel blockers. In severe CAE or history of MI, the addition of anticoagulation therapy after assessing bleeding risk may be warranted. In acute MI, the large thrombus burden in the dilated segment makes the percutaneous approach very challenging. Aspiration attempts can result in distal thromboembolization. Survival is better in bypass grafting than with medical therapy. Nonetheless, bypass grafting does not improve survival in atherosclerotic CAE. Depending on the physical characteristics of aneurysm, different surgical approaches can be sought; however, the ideal one is unclear.

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Section: Coronary Artery Ectasia In Sickle Cell Diseasementioning

confidence: 99%

Coronary Artery Ectasia in Atherosclerotic Coronary Artery Disease, Inflammatory Disorders, and Sickle Cell Disease

Dahhan

2015

Cardiovascular Therapeutics

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“…Occlusions of the microcirculation, as well as infections, are important factors that stimulate oxidative stress, production of cytokines, and acute-phase proteins. Cytokines may participate in several mechanisms that contribute to vaso-occlusive pathogenesis in SCA, including vascular endothelial activation, induction of red cell and leukocyte adhesion to vascular endothelium, development of vascular intimal hyperplasia, platelet activation, endothelin-1 production, and dysregulation of endothelial apoptosis [3]. Although alterations in a number of inflammatory, anti-inflammatory cytokines, and inflammatory biomarkers have been related previously, reports have been conflicting, and a conclusive role for cytokines in SCA remains to be established.…”

Section: Introductionmentioning

confidence: 99%

Altered levels of cytokines and inflammatory mediators in plasma and leukocytes of sickle cell anemia patients and effects of hydroxyurea therapy

Lanaro

Franco‐Penteado

Albuqueque

et al. 2008

Journal of Leukocyte Biology

189

142

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Inflammation, cell adhesion to vascular endothelium, and endothelial injury contribute to sickle cell anemia (SCA) vaso-occlusion. Although alterations in inflammatory cytokines and biomarkers have been related, reports have been conflicting, and a conclusive role for these molecules in the disease remains to be established. Furthermore, the effect of hydroxyurea therapy (HU) on the release of inflammatory mediators is not understood. This study aimed to determine plasma levels and leukocyte gene expressions of inflammatory mediators in healthy controls, steady-state SCA patients, and SCA patients on HU therapy. TNF-␣, IL-8, and PGE 2 levels were significantly higher in the plasma of SCA individuals when compared with control individuals. HU therapy was associated with a significant reversal of aug-

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“…Here we show that SPB affects the expression of genes that are relevant to the SCD pathophysiology by cells from a bone marrow microcirculation cell line. Abnormalities of the vascular tone regulation and increased RBC adhesion to the endothelium have been shown to be major participants to the initiation of vaso-occlusion in SCD [18]. ET-1 is a major factor of vasoconstriction [19] and smooth muscle proliferation, which is produced by ECs after hypoxia and/or ischemia [20].…”

Section: Discussionmentioning

confidence: 99%

Sodium phenyl butyrate downregulates endothelin‐1 expression in cultured human endothelial cells: Relevance to sickle‐cell disease

et al. 2007

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As hydroxyurea (HU), sodium phenyl butyrate (SPB) is known to induce fetal hemoglobin (HbF) expression and thus shows potentials for sickle-cell disease (SCD) treatment. More recently, few studies suggested that endothelial cells (ECs), a major pathophysiological actor of SCD, are also a target of SPB. Here, we show that SPB, as HU, reduces endothelin-1 mRNA expression and peptide release by human ECs in culture. SPB increases VCAM-1 and ICAM-1 mRNAs and soluble ICAM-1 release. Both drugs have a cumulative effect on ICAM-1 expression. We conclude that SPB, as HU, also affects the expression of molecules important to the pathophysiology of SCD, in addition to its effect on HbF. Its potential as an alternative or adjuvant drug in SCD treatment warrants further investigations. Am. J. Hematol. 82:357-362, 2007. V V C 2007 Wiley-Liss, Inc.

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The role of cytokines in sickle cell disease

Cited by 98 publications

References 0 publications

Coronary Artery Ectasia in Atherosclerotic Coronary Artery Disease, Inflammatory Disorders, and Sickle Cell Disease

Coronary Artery Ectasia in Atherosclerotic Coronary Artery Disease, Inflammatory Disorders, and Sickle Cell Disease

Altered levels of cytokines and inflammatory mediators in plasma and leukocytes of sickle cell anemia patients and effects of hydroxyurea therapy

Sodium phenyl butyrate downregulates endothelin‐1 expression in cultured human endothelial cells: Relevance to sickle‐cell disease

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