title: Cytokine inhibitors in patients with heart failure and impaired functional capacity.
abstract: Cytokines are proteins with pleiotropic biological effects, but the pathophysiologic role of cytokine inhibitors in advanced cardiac disease remains unclear. We assessed the levels of tumor necrosis factor (TNF)-alpha and its soluble receptors I (sTNF-RI) and II (sTNF-RII), soluble interleukin-1 receptor antagonist (sIL-1 Ra), and interleukin-6 soluble receptor (IL-6 sR) in sera from 11 patients with severe chronic congestive heart failure (mean left ventricular ejection fraction 19 +/- 6%; mean symptom-limited oxygen consumption 13 +/- 4 ml/min per kg) and 11 healthy volunteers. The serum concentrations of TNF, sTNF-RI, and sIL-1 Ra, but not of sTNF-RII and IL-6 sR, were significantly increased in heart failure patients. Importantly, their symptom-limited oxygen consumption was strongly associated with both sTNF-RI (R = -0.68, p = 0.04) and sIL-1 Ra (R = -0.77, p = 0.01). These results suggest that cytokine inhibitors from different receptor families may be involved in functional disability, a characteristic feature in patients with severe congestive heart failure. Understanding the response of cytokine inhibitors to heart failure might have therapeutic value as interventions against cytokines become available.
authors.affiliation: Department of Cardiology, Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire, Montpellier, France.
authors.forename: E
authors.initials: E
authors.lastname: Missov
authors.forename: A
authors.initials: A
authors.lastname: Campbell
authors.forename: B
authors.initials: B
authors.lastname: Lebel
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood; D016022:Case-Control Studies; D016207:Cytokines / Q000037:antagonists & inhibitors*; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000097:blood; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D012795:Sialoglycoproteins / Q000097:blood; D012995:Solubility
chemical_list: D015703:Antigens, CD; D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins