Circulating levels of cytokines and their site of production in patients with mild to severe chronic heart failure.
BACKGROUND
Patients with chronic heart failure have elevated levels of proinflammatory cytokines; however, the mechanism for their increased expression and the site of their production are unknown.


METHODS
Twenty-two patients with heart failure, New York Heart Association functional class II to IV, underwent hemodynamic evaluation and echocardiographic study. Blood samples for cytokine evaluation were performed in the ascending aorta, coronary sinus, inferior vena cava, and hepatic vein. Levels of tumor necrosis factor-alpha (TNF-alpha), its soluble receptors sTNF-RI and sTNF-RII, interleukin-6 (IL-6), IL-6 soluble receptor, soluble gp130, interleukin-2 soluble receptor, and soluble Fas were measured with enzyme-linked immunosorbent assay kits.


RESULTS
IL-6 concentrations were higher in class IV patients than in class III patients, which in turn were higher than those in class II. TNF-alpha, sTNF-RI, and sTNF-RII were higher in class IV patients than in class III and II patients. Significant correlations were found between IL-6 concentrations and left ventricular end-systolic volume (r = 0.64; P <.001), pulmonary wedge pressure (r = 0.56; P <.01), and left ventricular ejection fraction (r = -0.56; P <.01). No correlation was found between TNF-alpha and its soluble receptors and left ventricular volumes or hemodynamic measures. Finally, no difference in cytokine concentrations was found among the different sample sites.


CONCLUSIONS
Among inflammatory cytokines, IL-6 concentrations better reflect the hemodynamic derangement in patients with heart failure. No cardiac or gut production of cytokines occurs in patients with mild to severe heart failure.
Petretta
M
M
Department of Internal Medicine, Cardiology, and Heart Surgery, University of Naples Federico II, Italy.
Condorelli
G L
GL
Spinelli
L
L
Scopacasa
F
F
de Caterina
M
M
Leosco
D
D
Vicario
M L
ML
Bonaduce
D
D
D000328:Adult; D001011:Aorta; D002303:Cardiac Output, Low / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha