title: Angiotensin II type 1 receptor antagonist decreases plasma levels of tumor necrosis factor alpha, interleukin-6 and soluble adhesion molecules in patients with chronic heart failure.
abstract: OBJECTIVE
  To evaluate the effects of an angiotensin (Ang II) type 1 receptor antagonist on immune markers in patients with congestive heart failure (CHF).
  
  
  BACKGROUND
  Ang II stimulates production of immune factors via the Ang II type 1 receptor in vitro, and the long-term effects of Ang II type 1 receptor antagonists on plasma markers of immune activation are unknown in patients with CHF.
  
  
  METHODS
  Twenty-three patients with mild to moderate CHF with left ventricular dysfunction were randomly divided into two groups: treatment with Ang II type 1 receptor (candesartan cilexetil) (n = 14) or placebo (n = 9). We measured plasma levels of immune factors such as tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1). We also measured plasma levels of the neurohumoral factors such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP), a biological marker of ANP and BNP.
  
  
  RESULTS
  Plasma levels of TNFalpha, IL-6, sICAM-1 and sVCAM-1 were increased in the 23 CHF patients compared with normal subjects and significantly decreased after 14 weeks of candesartan cilexetil treatment, but did not change in the placebo group. Plasma levels of BNP, which is a marker of ventricular injury, significantly decreased, and the molar ratio of plasma cGMP to cardiac natriuretic peptides (ANP + BNP) was significantly increased after candesartan cilexetil treatment, but did not change in the placebo group.
  
  
  CONCLUSIONS
  These findings suggest that 14 weeks of treatment with an Ang II type 1 receptor antagonist (candesartan cilexetil) decreased plasma levels of the immune markers such as TNFalpha, IL-6, sICAM-1 and sVCAM-1 and that it improved the biological compensatory action of endogenous cardiac natriuretic peptides in patients with mild to moderate CHF.
authors.affiliation: First Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Japan. tutamoto@belle.shiga-med.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Tsutamoto
authors.forename: A
authors.initials: A
authors.lastname: Wada
authors.forename: K
authors.initials: K
authors.lastname: Maeda
authors.forename: N
authors.initials: N
authors.lastname: Mabuchi
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Tsutsui
authors.forename: M
authors.initials: M
authors.lastname: Ohnishi
authors.forename: M
authors.initials: M
authors.lastname: Sawaki
authors.forename: M
authors.initials: M
authors.lastname: Fujii
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: M
authors.initials: M
authors.lastname: Kinoshita
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000097:blood; D001562:Benzimidazoles / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000097:blood*; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013318:Stroke Volume; D013777:Tetrazoles; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; D015815:Cell Adhesion Molecules; D015850:Interleukin-6; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D020097:Natriuretic Peptide, Brain; D018799:Intercellular Adhesion Molecule-1; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; C077793:candesartan cilexetil