title: Cytokine generation capacities of monocytes are reduced in patients with severe heart failure.
abstract: BACKGROUND
  Immunologic mechanisms mediated by proinflammatory cytokines have been implicated in the pathogenesis of heart failure. Although monocytes are the major source of such cytokines, little is known about their cytokine generation capacities in heart failure.
  
  
  METHODS
  We measured plasma levels of 7 major monocyte-related cytokines and the generation capacity of monocytes for 3 cytokines (interleukin-1alpha, interleukin-1beta, and tumor necrosis factor-alpha) on stimulation by lipopolysaccharide in 45 consecutive patients with heart failure and 27 controls. The cytokine levels were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The generation capacities of monocytes for all 3 cytokines were decreased in patients with worsened outcome during hospitalization and the monocyte capacities were significantly reduced in patients with severe heart failure (New York Heart Association class IV). There was a significant negative correlation between the cytokine generation capacities of monocytes and the plasma cortisol levels. Moreover, cortisol significantly inhibited the cytokine production by lipopolysaccharide-stimulated monocytes ex vivo.
  
  
  CONCLUSIONS
  These results indicate that the cytokine generation capacities of monocytes are reduced in patients with severe heart failure, partly because of the negative regulation by cortisol. Because monocytes and cytokines play a central role in immune responses, this reduced monocyte function may be involved in part in the pathophysiology of severe heart failure.
authors.affiliation: Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan. shimo@cardio.med.kyushu-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Shimokawa
authors.forename: M
authors.initials: M
authors.lastname: Kuroiwa-Matsumoto
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006854:Hydrocortisone