title: Beta blocker and angiotensin-converting enzyme inhibitor therapy is associated with decreased Th1/Th2 cytokine ratios and inflammatory cytokine production in patients with chronic heart failure.
abstract: OBJECTIVE
  To examine the potential impact of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, medications which modulate beta-adrenergic signaling, on immune function in patients with chronic heart failure (HF).
  
  
  METHODS
  118 patients attending an HF center were tested for circulating levels of norepinephrine (NE), T cells and the inflammation-associated cytokine interleukin 6 (IL-6). Levels of the cytokines interferon-gamma (IFNgamma), IL-10, and tumor necrosis factor-alpha (TNFalpha) produced by cultured peripheral blood mononuclear cells (PBMC) were measured in culture supernatants following T cell stimulation in vitro.
  
  
  RESULTS
  NE levels were significantly lower in patients receiving ACE inhibitors (p = 0.0263), with a trend toward lower NE in patients receiving beta-blockers. All patients exhibited relatively normal levels of T cells, and there was a trend toward higher levels of total (CD3+) and helper (CD4+) T cells (p = 0.0578 and 0.0932, respectively) in patients receiving either type of medication. The ratios of Th1 (IFNgamma) to Th2 (IL-10) cytokines were lower in patients receiving a combination of beta-blocker and ACE inhibitor therapy (p = 0.0373). NYHA class was a significant predictor of serum IL-6 (p < 0.0001). There was a trend toward lower levels of serum IL-6 in patients receiving both types of medications (p = 0.0606). TNFalpha production by CD3/CD28-stimulated PBMC was significantly lower in patients receiving ACE inhibitor medications (p = 0.0223).
  
  
  CONCLUSIONS
  These results suggest that high sympathetic tone associated with chronic HF affects Th1/Th2 and inflammatory cytokine production, and that these effects can be modulated by medications. In addition to improvement in clinical parameters relating to cardiovascular function, beta-blocker and ACE inhibitor medications also appear to have a beneficial effect on the immune system in HF.
authors.affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, Calif., USA.
authors.forename: Julia R
authors.initials: JR
authors.lastname: Gage
authors.forename: Gregg
authors.initials: G
authors.lastname: Fonarow
authors.forename: Michele
authors.initials: M
authors.lastname: Hamilton
authors.forename: Mel
authors.initials: M
authors.lastname: Widawski
authors.forename: Otoniel
authors.initials: O
authors.lastname: Martínez-Maza
authors.forename: Donna L
authors.initials: DL
authors.lastname: Vredevoe
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood / Q000187:drug effects* / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects* / Q000276:immunology; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D017252:CD3 Complex; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D009638:Norepinephrine