interleukin-8 and beta-Thalassemia

β-Thalassemia major (β-TM) is an inherited disorder of hemoglobin (Hb) production, which can cause severe anemia. A compromised immune system has been observed in patients with β-TM, whereas cytokines have a major role in immune modulation. Interleukin-4 (IL-4), IL-8, IL-13 and transforming growth factor-β (TGF-β) are critical in initiating pro-inflammatory responses, and the serum levels of those cytokines may be involved in the pathophysiology of β-thalassemia (β-thal). To assess this hypothesis, we studied 23 pediatric patients with β-TM by measuring serum levels of IL-4, IL-8, IL-13 and TGF-β, as well as evaluating infection frequency per year, total number of transfusions and serum ferritin (SF) levels, together with age-matched healthy controls. We found that patients with β-thal had higher IL-8, IL-13 and TGF-β concentrations than normal controls, whereas markedly decreased serum IL-4 level was documented in patients with β-TM. Serum IL-4 level of β-thal patients showed a negative significant correlation with infection frequency, total number of transfusions and SF levels. On the contrary, serum levels of IL-8, IL-13 and TGF-β exerted a positive relationship with those clinical parameters. Taken together, our study implies that dysregulated cytokine profile might contribute to iron overloads and impair immune cell functions, thus serving as useful biomarkers for diagnosis and evaluation of β-TM in the future. Our study sheds new light on the pathogenesis of β-TM.

Topics: beta-Thalassemia; Child; Cytokines; Humans; Interleukin-13; Interleukin-4; Interleukin-8; Transforming Growth Factor beta

Thalassemia major (TM) is characterized by abnormal hemoglobin synthesis, which results in decreased oxygen delivery to the tissues, ineffective erythropoiesis and iron overload. The purpose of this study was to find out the predominant type of lung mechanical abnormalities in TM patients, the prevalence of the change in pulmonary diffusing capacity and to search the association of cytokines with pulmonary function tests (PFTs).. TM patients (n = 26) who were on regular transfusion program were included in the study. Pretransfusional and posttransfusional PFTs were performed. Before transfusion, blood samples were collected for complete blood count, serum ferritin, zinc, transforming growth factor-β1 (TGF-β1), interleukin (IL)-8 and IL-10 levels.. Obstructive lung pattern was the predominant pulmonary sequela. Male gender was the main risk factor for pulmonary function abnormality. Because of very low values, serum IL-10 levels of all patients were undetectable, and serum IL-8 levels could be measured only in six patients. Median serum IL-8 level was higher in patients with abnormal PFT. Pretransfusional single breath diffusion of carbon monoxide (DLCO ) correlated negatively with serum TGF-β1 and ferritin levels. After transfusion, there was a statistically significant decrease in forced expiratory volume in 1 s, forced expiratory flow between 25% and 75% of vital capacity, and airway conductance but significant increase in DLCO .. Although they are mostly asymptomatic, TM patients have important PFT abnormalities. Blood transfusion may have an acute deleterious effect on pulmonary functions. The disturbed pulmonary functions were found to correlate with IL-8 and TGF-β levels. Relations of different cytokines with different PFT parameters suggest that the immune system is effective pulmonary dysfunction.

Topics: Adolescent; beta-Thalassemia; Blood Transfusion; Child; Cytokines; Female; Ferritins; Humans; Interleukin-10; Interleukin-8; Lung; Male; Respiratory Function Tests; Transforming Growth Factor beta1; Young Adult

The aim of this cross-sectional study is to compare the local and systemic levels of soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteoprotegerin (OPG), a proliferation-inducing ligand (APRIL), B-cell activating factor (BAFF), interleukin (IL)-6, and IL-8 in biofluids of patients with thalassemia major (TM) with or without gingivitis.. Seventy-seven patients are included in this study (TM, n = 29; systemically healthy, n = 48). Gingival crevicular fluid (GCF), saliva, and serum levels of IL-6, IL-8, sRANKL, OPG, BAFF, and APRIL were determined by enzyme-linked immunosorbent assay. Data were analyzed by appropriate non-parametric or parametric statistical tests.. Median GCF, serum, and saliva levels for BAFF (P <0.001) and IL-6 and IL-8 (P <0.005) were higher in TM gingivitis than in systemically healthy gingivitis (P <0.001). GCF, serum, and saliva levels for APRIL, sRANKL, IL-6, and IL-8 were higher in TM than in systemically and periodontally healthy comparison groups (P <0.05). Positive correlations were found between bleeding on probing (BOP), plaque index (PI) scores, and GCF APRIL, serum sRANKL, serum OPG, and sRANKL concentrations in TM groups (P <0.05). Several significant positive correlations were found between BOP, PI scores, and biofluid parameters also in systemically healthy groups.. TM may have a role in the underlying systemic hematologic condition and potentially affect gingival inflammation via dysregulation of lymphocytes and increased activation of osteoclasts.

Topics: Adolescent; Adult; B-Cell Activating Factor; beta-Thalassemia; Cross-Sectional Studies; Dental Plaque Index; Female; Gingival Crevicular Fluid; Gingivitis; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Osteoprotegerin; Periodontal Index; RANK Ligand; Saliva; Tumor Necrosis Factor Ligand Superfamily Member 13; Young Adult

Topics: Adolescent; Adult; Anemia, Sickle Cell; beta-Thalassemia; Biomarkers; C-Reactive Protein; Case-Control Studies; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Vascular Cell Adhesion Molecule-1

Several immunological defects can be found in patients with beta-thalassaemia, among which the impairment of neurophil and macrophage phagocytic and killing functions and the production of some cytokines are the most important. It is known that interleukin-6 (IL-6) and interleukin-8 (IL-8) are important components of the pro-inflammatory response. The plasma levels of these cytokines may be relevant in the pathophysiology of beta-thalassaemia. To assess this hypothesis, the plasma IL-6 and IL-8 concentrations in patients with beta-thalassaemia, were investigated. Fourteen patients with thalassaemia major were studied by evaluating body iron status, iron supply for erythropoiesis, and plasma IL-6 and IL-8 levels, together with 12 age-matched healthy controls. The plasma levels of IL-6 and IL-8 were determined by enzyme-linked immunosorbent assay (ELISA). Patients with beta-thalassaemia were found to have higher IL-8 concentrations than normal controls (p < 0.001) and plasma IL-6 concentrations increased significantly in the beta-thalassaemic patients compared with control subjects (p = 0.01). Serum ferritin levels of beta-thalassaemic patients were significantly higher than those of control groups (p < 0.05). IL-8 levels correlated with ferritin levels (r = 0.694; p < 0.05) and the total number of transfusions (r = 0.64; p < 0.05). Plasma IL-6 levels in beta-thalassaemic patients did not correlate with any clinical, haematological or biochemical parameters. It was also found that plasma IL-8 levels in the patients who had blood transfusions over 100 times were significantly higher than those of under 100 times (p < 0.05), whereas there was no statistical difference for IL-6. Markedly increased plasma IL-6 and IL-8 levels were documented in patients with beta-thalassaemia. Increased production of IL-6 and IL-8 might have contributed to abnormalities in iron metabolism and it is probably due to overstimulation of macrophages. Before a clinical value can be ascribed to these changes in plasma cytokine levels in beta-thalassaemia, the follow-up samples of larger series of patients with 8-thalassaemia should be evaluated.

Topics: Adolescent; Adult; beta-Thalassemia; Blood Transfusion; Case-Control Studies; Child; Child, Preschool; Deferoxamine; Female; Ferritins; Humans; Immune System; Interleukin-6; Interleukin-8; Male; Splenectomy

Neutrophil chemotactic and functional defects occur in beta-thalassemia and in patients after bone marrow transplantation (BMT). Interleukin-8 (IL-8) is a novel chemotactic and activating peptide for neutrophils and can be detected in the circulation. IL-8 serum concentrations were evaluated in 30 beta-thalassemic patients before and after BMT. Serial samples from 16 patients were also studied. Fourteen sera from healthy children, 43 patients with chronic viral hepatitis, 16 patients on chronic transfusion treatment for various hematologic disorders, and 28 healthy adults were studied as controls. IL-8 was evaluated by an enzyme-linked immunosorbent assay. Patients with beta-thalassemia had higher IL-8 concentrations than did normal controls, patients with liver disease, and patients on chronic transfusion. beta-Thalassemic patients with severe liver siderosis and fibrosis had the highest IL-8 concentrations. After BMT in patients with successful engraftment, IL-8 concentrations decreased significantly. In contrast, in patients with acute graft-versus-host disease (GVHD), IL-8 concentrations were not statistically different from the concentrations found before BMT and were higher than in patients with no complications and patients with graft rejection. IL-8 may play a part in the immune dysregulation that occurs in beta-thalassemia and may be involved in the immune mechanisms leading to GVHD.

Topics: Adolescent; Adult; beta-Thalassemia; Biomarkers; Biopsy; Blood Transfusion; Bone Marrow Transplantation; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Graft vs Host Disease; Hepatitis, Viral, Human; Humans; Interleukin-8; Liver; Male; Reference Values; Time Factors