title: Enhanced gene expression of chemokines and their corresponding receptors in mononuclear blood cells in chronic heart failure--modulatory effect of intravenous immunoglobulin.
abstract: OBJECTIVE
  We sought to study the gene expression of chemokines and their corresponding receptors in mononuclear blood cells (MNCs) from patients with chronic heart failure (CHF), both of which were cross-sectional and longitudinal studies during therapy with intravenous immunoglobulin (IVIg).
  
  
  BACKGROUND
  We have recently demonstrated that IVIg improves left ventricular ejection fraction (LVEF) in patients with CHF. Based on the potential pathogenic role of chemokines in CHF, we hypothesized that the beneficial effect of IVIg may be related to a modulatory, effect on the expression of chemokines and their receptors in MNCs.
  
  
  METHODS
  We examined: 1) the gene expression of C, CC and CXC chemokines and their receptors in MNCs from 20 patients with CHF and 10 healthy blood donors; and 2) the expression of these genes in MNCs from 20 patients with CHF randomized in a double-blind fashion to therapy with IVIg or placebo for 26 weeks.
  
  
  RESULTS
  Our main findings in CHF were: 1) markedly raised gene expression of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and interleukin (IL)-8; 2) enhanced gene expression of their corresponding receptors; 3) modulation in a normal direction of this abnormal chemokine and chemokine receptor gene expression during IVIg, but not during placebo therapy; 4) down-regulation of MIP-1alpha, MIP-1beta and IL-8 during IVIg at the protein level in plasma; and 5) a correlation between down-regulation of MIP-1alpha gene expression and improved LVEF during IVIg therapy.
  
  
  CONCLUSIONS
  Our results further support a pathogenic role for chemokines in CHF and suggest that IVIg may represent a novel therapeutic approach, with the potential to improve LVEF in patients with CHF, possibly by modulatory effects on the chemokine network.
authors.affiliation: Department of Cardiology, University of Oslo, The National Hospital, Norway. j.k.damas@klinmed.uio.no
authors.forename: J K
authors.initials: JK
authors.lastname: Damås
authors.forename: L
authors.initials: L
authors.lastname: Gullestad
authors.forename: H
authors.initials: H
authors.lastname: Aass
authors.forename: S
authors.initials: S
authors.lastname: Simonsen
authors.forename: J G
authors.initials: JG
authors.lastname: Fjeld
authors.forename: L
authors.initials: L
authors.lastname: Wikeby
authors.forename: T
authors.initials: T
authors.lastname: Ueland
authors.forename: H G
authors.initials: HG
authors.lastname: Eiken
authors.forename: S S
authors.initials: SS
authors.lastname: Frøland
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D000368:Aged; D019744:Chemokines, C / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*; D013318:Stroke Volume / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D019744:Chemokines, C; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016756:Immunoglobulins, Intravenous; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D019707:Receptors, Chemokine