Altered levels of pro-inflammatory cytokines in sickle cell disease patients during vaso-occlusive crises and the steady state condition.

OBJECTIVE This study aimed to evaluate serum levels of pro-inflammatory cytokines and TGF-β in sickle cell disease (SCD) patients, and to compare the results during vaso-occlusive crisis (VOC) or steady state (StSt) conditions. METHODS 54 SCD patients (37HbSS and 17Sβ(+)Thal) were enrolled in the study and evaluated in two groups as follows; group A consisted of 39 VOC patients and group B comprised 15 StSt patients. Nineteen healthy volunteers were included as controls. Circulating levels of IL-1, IL-6, IL-8, IL-17,TNF-α and TGF-β were measured using ELISA. RESULTS Patients in VOC showed higher mean levels of all cytokines than those found in steady-state patients, but this was only marginally significant for IL-8 levels (P = 0.08). Increased levels of TGF-β and IL-17 were found in StSt patients versus normal controls (P = 0.004 and P<0.0001 respectively). A positive correlation was observed between IL-8 and IL-17 in both groups of patients (P = 0.002 and P = 0.005 respectively). Decreased levels of TNF-α, IL-1β and IL-17 were found in hydroxyurea-treated patients. Additionally, significantly higher levels of IL-6 and IL-8 were observed in hydroxyurea-treated and untreated patients than in controls respectively (P = 0.04 and P = 0.01). CONCLUSIONS Our findings indicate that pro-inflammatory cytokines, especially IL-8 and IL-17, could be used as related markers for assessing disease severity, and consequently therapeutic intervention.

[1]  M. Reis,et al.  TNF-alpha and IL-8: serum levels and gene polymorphisms (-308G>A and -251A>T) are associated with classical biomarkers and medical history in children with sickle cell anemia. , 2011, Cytokine.

[2]  M. Reis,et al.  Arginase levels and their association with Th17-related cytokines, soluble adhesion molecules (sICAM-1 and sVCAM-1) and hemolysis markers among steady-state sickle cell anemia patients , 2010, Annals of Hematology.

[3]  V. Kuchroo,et al.  Interleukin-17 and type 17 helper T cells. , 2009, The New England journal of medicine.

[4]  S. Saad,et al.  Altered levels of cytokines and inflammatory mediators in plasma and leukocytes of sickle cell anemia patients and effects of hydroxyurea therapy , 2009, Journal of leukocyte biology.

[5]  S. Gaffen An overview of IL-17 function and signaling. , 2008, Cytokine.

[6]  K. Ataga,et al.  Fibronectin bridges monocytes and reticulocytes via integrin α4β1 , 2008, British journal of haematology.

[7]  M. Telen,et al.  Adhesion molecules and hydroxyurea in the pathophysiology of sickle cell disease , 2008, Haematologica.

[8]  K. Ataga,et al.  β‐Thalassaemia and sickle cell anaemia as paradigms of hypercoagulability , 2007, British journal of haematology.

[9]  C. Elie,et al.  Long-term hydroxyurea treatment in children with sickle cell disease: tolerance and clinical outcomes. , 2006, Haematologica.

[10]  J. Scott,et al.  Long-term hydroxyurea therapy for infants with sickle cell anemia: the HUSOFT extension study. , 2005, Blood.

[11]  J. Hibbert,et al.  Proinflammatory Cytokines and the Hypermetabolism of Children with Sickle Cell Disease , 2005, Experimental biology and medicine.

[12]  A. Pathare,et al.  Cytokine profile of sickle cell disease in Oman , 2004, American journal of hematology.

[13]  S. Saad,et al.  Increased adhesive properties of eosinophils in sickle cell disease. , 2004, Experimental Hematology.

[14]  I. Okpala The intriguing contribution of white blood cells to sickle cell disease - a red cell disorder. , 2004, Blood reviews.

[15]  P. Frenette Sickle Cell Vasoocclusion: Heterotypic, Multicellular Aggregations Driven by Leukocyte Adhesion , 2004, Microcirculation.

[16]  R. Osarogiagbon,et al.  The Endothelial Biology of Sickle Cell Disease: Inflammation and a Chronic Vasculopathy , 2004, Microcirculation.

[17]  E. Perlin,et al.  Plasma levels of TNF-alpha in sickle cell patients receiving hydroxyurea. , 2004, Hematology.

[18]  R. Nagel,et al.  Sickle-cell disease. , 2004, Lancet.

[19]  A. Pathare,et al.  Cytokines in Sickle Cell Disease , 2003, Hematology.

[20]  C. Pegelow,et al.  Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. , 2003, JAMA.

[21]  M. Telen,et al.  Erythrocyte adhesion in sickle cell disease. , 2003, Current hematology reports.

[22]  I. Roberts,et al.  The role of hydroxyurea in sickle cell disease , 2003, British journal of haematology.

[23]  J. Goldman,et al.  Relationship between the clinical manifestations of sickle cell disease and the expression of adhesion molecules on white blood cells , 2002, European journal of haematology.

[24]  M. Gonçalves,et al.  Interleukin 8 as a vaso-occlusive marker in Brazilian patients with sickle cell disease. , 2001, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[25]  S. Ballas,et al.  Elevated serum and bronchoalveolar lavage fluid levels of interleukin 8 and granulocyte colony‐stimulating factor associated with the acute chest syndrome in patients with sickle cell disease , 2000, British journal of haematology.

[26]  E. Hatzimichael,et al.  The role of cytokines in sickle cell disease , 2000, Annals of Hematology.

[27]  S. Taylor,et al.  In vivo production of type 1 cytokines in healthy sickle cell disease patients. , 1999, Journal of the National Medical Association.

[28]  A. Duits,et al.  Neutrophil activation in sickle cell disease , 1999, Journal of leukocyte biology.

[29]  D. Labie,et al.  Long-term hydroxyurea treatment in young sickle cell patients. , 1999, Current opinion in hematology.

[30]  R. Nagel,et al.  Circulating cytokines response and the level of erythropoiesis in sickle cell anemia , 1999, American journal of hematology.

[31]  A. Duits,et al.  Elevated IL‐8 levels during sickle cell crisis , 1998, European journal of haematology.

[32]  S. Douglas,et al.  Serum levels of substance P are elevated in patients with sickle cell disease and increase further during vaso-occlusive crisis. , 1998, Blood.

[33]  K. Bourantas,et al.  Acute phase proteins and interleukins in steady state sickle cell disease , 1998, European journal of haematology.

[34]  I. Okpala,et al.  Peripheral blood neutrophil count and candidacidal activity correlate with the clinical severity of sickle cell anaemia (SCA) , 1998, European journal of haematology.

[35]  S. Taylor,et al.  Type 2 cytokine serum levels in healthy sickle cell disease patients. , 1997, Journal of the National Medical Association.

[36]  H. Bunn Pathogenesis and treatment of sickle cell disease. , 1997, The New England journal of medicine.

[37]  B. Setty,et al.  Vascular cell adhesion molecule-1 is involved in mediating hypoxia-induced sickle red blood cell adherence to endothelium: potential role in sickle cell disease. , 1996, Blood.

[38]  M L Terrin,et al.  Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. , 1995, The New England journal of medicine.

[39]  O. Platt,et al.  Sickle reticulocytes adhere to VCAM-1. , 1995, Blood.

[40]  O. Platt,et al.  Mortality in sickle cell disease. Life expectancy and risk factors for early death. , 1994, The New England journal of medicine.