interleukin-8 and Cardiomyopathy--Dilated

Inflammation and matrix degradation may play a pathogenic role in chronic heart failure (CHF), and therefore, we examined whether thalidomide, a drug with potential immunomodulating and matrix-stabilizing properties, could improve left ventricular (LV) function in patients with CHF secondary to idiopathic dilated cardiomyopathy (IDCM) or coronary artery disease (CAD).. Fifty-six patients with CHF and an LV ejection fraction (LVEF) <40% who were already on optimal conventional cardiovascular treatment were randomized to thalidomide (25 mg QD increasing to 200 mg QD) or placebo and followed up for 12 weeks. Our main findings were as follows: (1) During thalidomide treatment but not during placebo, there was a marked increase in LVEF (&7 EF units) along with a significant decrease in LV end-diastolic volume and heart rate. (2) This improvement in LVEF was accompanied by a decrease in matrix metalloproteinase-2 without any changes in its endogenous tissue inhibitor, suggesting a matrix-stabilizing net effect. (3) Thalidomide also induced a decrease in total neutrophil count and an increase in plasma levels of tumor necrosis factor-alpha, suggesting both proinflammatory and antiinflammatory effects. (4) The effect of thalidomide on LVEF was more marked in IDCM than in CAD, possibly partly reflecting that the former group was able to tolerate a higher thalidomide dosage.. Although our results must be confirmed in larger studies that also examine the effects on morbidity and mortality, our findings suggest a role for thalidomide in the management of CHF in addition to traditional cardiovascular medications.

Topics: Aged; Cardiomyopathy, Dilated; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Heart Failure; Humans; Immune System; In Vitro Techniques; Interleukin-8; Matrix Metalloproteinase 2; Middle Aged; Placebos; Thalidomide; Tissue Inhibitor of Metalloproteinase-1; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left

Chronic heart failure (CHF) is associated with a higher risk for diabetes mellitus. Retinol binding protein 4 (RBP 4) is an adipose tissue-derived protein with pro-diabetogenic effects. A complete understanding of the association of CHF and insulin resistance remains elusive. The purpose of this study was to examine the relationship between CHF and diabetes mellitus.. Plasma levels of RBP 4, insulin, and interleukins (IL) 2, 8, and 10, were assessed in patients with dilated cardiomyopathy (DCM, n = 53), dilated inflammatory cardiomyopathy (DCMi, n = 54), and controls (n = 20). In addition, a possible mechanism of RBP 4 regulation was examined in adipocytes in vitro. Plasma levels of RBP 4 and insulin were measured by a specific ELISA. Interleukin concentrations were obtained by multiplex ELISA. Cell culture with 3T3-L1 adipocytes was performed to measure RBP 4 mRNA expression after stimulation with IL-8. RBP 4 levels were significantly increased in patients with DCMi (52.95 +/- 20.42 microg/mL) compared with DCM (35.54 +/- 23.08 microg/mL) and the control group (27.3 +/- 18.51 microg/mL). RBP 4 was positively correlated with IL-8 (r=0.416, P < 0.05) in human plasma in patients with DCMi. Moreover, increased insulin resistance was observed in patients with DCMi compared with the control and DCM groups. In vitro, IL-8 induced a significant upregulation of RBP 4 mRNA expression in adipocytes.. Elevated RBP 4 plasma concentrations, induced by IL-8, might be one mechanism leading to a higher incidence of diabetes in patients with DCMi.

Topics: 3T3 Cells; Adipocytes; Adult; Animals; Cardiomyopathies; Cardiomyopathy, Dilated; Cells, Cultured; Diabetes Complications; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Humans; Inflammation; Insulin; Interleukin-10; Interleukin-2; Interleukin-8; Male; Mice; Middle Aged; Retinol-Binding Proteins, Plasma

Cardiac transplantation faces the serious problem of lack of donors and it is estimated that 20 to 40% of the patients die while waiting for heart transplantation. For these patients, the use of mechanical circulatory assist devices is the only choice of survival while waiting for a donor. In Brazil, the experience with mechanical circulatory support is limited and there is no regular program regarding the use of these devices as a bridge to heart transplantation.. To evaluate the hemodynamic performance and the systemic inflammatory response during the clinical use of the InCor-type ventricular assist device (VAD-InCor) as a bridge to heart transplantation.. Between October 2003 and April 2006, 11 patients in the waiting list for heart transplantation presented hemodynamic deterioration due to refractory cardiogenic shock. Seven of these patients were submitted to VAD-InCor implantation for left ventricular assistance. The etiologic diagnosis was Chagas' disease in 5 patients and idiopathic dilated cardiomyopathy in 2.. The duration of left ventricular assistance ranged from 14 to 42 days (mean 26.2 days). During this period, the hemodynamic performance of the DAV-InCor was adequate to support a normal hemodynamic state. There was normalization of central venous oxygen saturation and serum lactate. Two patients were submitted to heart transplantation, while the other 5 patients died under assistance due to infection and multiple organ failure.. The performance of the VAD-InCor, in the hemodynamic behavior of the studied patients, was adequate for the maintenance of a satisfactory circulatory state during the studied period. There was improvement in the tissue perfusion parameters and maintenance of systemic inflammatory response signs. There was a high incidence of complications; however, complications related to the device, which could compromise the safety of its use, were not demonstrated.

Topics: Adult; Biomarkers; C-Reactive Protein; Cardiomyopathy, Dilated; Chagas Cardiomyopathy; Female; Heart Transplantation; Heart-Assist Devices; Hemodynamics; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Middle Aged; Statistics, Nonparametric; Tumor Necrosis Factor-alpha; Waiting Lists

Diminished cardiac contractility associated with inflammatory infiltration may be mediated by the release of interleukins. To test this hypothesis, we assessed the presence of interleukin and interleukin-receptor mRNAs in non-failing human heart and in endomyocardial biopsies from patients with dilated cardiomyopathy or inflammatory myocarditis. Only those interleukins expressed by non-circulating cells (interleukin-1 beta, -4, and -8) were detected in samples of human heart while interleukins specific for activated leukocytes (interleukins-1 alpha and -2) were not detected in any samples. While interleukin-1-receptor mRNA was present in samples from non-failing hearts and those with idiopathic myopathy, it was absent from patients with inflammatory myocarditis, suggesting receptor mRNA down-regulation.

Topics: Base Sequence; Cardiomyopathies; Cardiomyopathy, Dilated; Interleukin-1; Interleukin-2; Interleukin-4; Interleukin-8; Interleukins; Molecular Sequence Data; Myocarditis; Myocardium; Polymerase Chain Reaction; Receptors, Immunologic; Receptors, Interleukin-1; RNA, Messenger