title: Interleukin-6 and tumor necrosis factor-alpha levels increase in response to maximal exercise in patients with chronic heart failure.
abstract: Chronic heart failure (CHF) is characterized by the activation of neurohormones and cytokines. Strenuous exercise causes activation of both systems but the effect of acute bouts of exercise on cytokines is not known in patients with CHF. This study determined whether maximal exercise induces activation of cytokines in CHF. Plasma interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, epinephrine, norepinephrine, and atrial and brain natriuretic peptides (ANP and BNP) were determined before and after symptom-limited cardiopulmonary exercise testing in 80 patients with CHF (LVEF=38+/-1%, peak VO(2)=18.8+/-0.5 ml/min/kg) and age-matched 33 controls. Resting IL-6 (Controls vs. CHF: 1.3+/-0.2 vs. 2.5+/-0.3 pg/ml, P<0.001) and TNF-alpha (2.7+/-0.2 vs. 3.8+/-0.2 pg/ml, P<0.01) were elevated in CHF. LogIL-6 and logTNF-alpha were positively correlated (r=0.34 and r=0.35, respectively) with logplasma norepinephrine, and were negatively correlated (r=-0.39 and r=-0.32, respectively) with peak VO(2). Maximal exercise increased IL-6 and TNF-alpha both in controls and CHF (all P<0.01). Changes in IL-6 (DeltaIL-6) correlated with Deltaepinephrine (r=0.63, P<0.0001) and Deltanorepinephrine (r=0.57, P=0.0006) in controls, but not in CHF. DeltaTNF-alpha correlated with DeltaANP (r=0.28, P=0.01) only in CHF. In summary, cytokine activation at rest was associated with high plasma norepinephrine and exercise intolerance. Maximal exercise caused increases in IL-6 and TNF-alpha concentrations. Sympathetic activation seems to be important for the IL-6 increase during exercise in controls. In CHF, changes in ANP during exercise were associated with the exercise-induced increase in TNF-alpha, but still unknown mechanisms are involved for the cytokine activation during exercise.
authors.affiliation: Division of Cardiology, First Department of Internal Medicine, Tottori University Faculty of Medicine, Yonago, Japan. kinugawa@grape.med.tottori-u.ac.jp
authors.forename: Toru
authors.initials: T
authors.lastname: Kinugawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kato
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Ogino
authors.forename: Shuichi
authors.initials: S
authors.lastname: Osaki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tomikura
authors.forename: Osamu
authors.initials: O
authors.lastname: Igawa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hisatome
authors.forename: Chiaki
authors.initials: C
authors.lastname: Shigemasa
mesh_terms: D009320:Atrial Natriuretic Factor / Q000097:blood; D016022:Case-Control Studies; D002908:Chronic Disease; D004837:Epinephrine / Q000097:blood; D005080:Exercise Test; D005260:Female; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D009638:Norepinephrine; D004837:Epinephrine