Cytokines in chronic heart failure: possible interaction in the neurohormonal and the cytokine system at the cAMP level?
In recent years, the pathophysiological concept of chronic heart failure (CHF) has changed from an isolated hemodynamic view to a more complex concept involving neuroendocrine and inflammatory pathways. New therapeutic strategies, such as beta-blocker therapy, are based on these new concepts and provide clinical evidence for a clinical benefit in patients with CHF. The survival benefit of beta-blocker therapy in CHF has been related to neurohumoral regulation. Thus, evidence evolved showing that following beta-blocker therapy cytokine levels in CHF patients are altered. We have shown that the levels of soluble TNF receptor type 2 correlated well with cAMP in leukocytes. Data from clinical studies in adult and infant CHF patients have demonstrated that beta-blocker therapy is accompanied by altered cytokine, cytokine antagonist, and/or soluble cytokine receptor levels. These alterations may result from a dysregulated interaction of beta-adrenergic pathways and the cytokine system, and are possibly related to cAMP-dependent regulation of the release or shedding of these mediators.
Werner
Claudia
C
Institut für Pharmakologie und Toxikologie der Technischen Universität München, Germany.
Loppnow
Harald
H
Rauchhaus
Mathias
M
Wessel
Armin
A
Werdan
Karl
K
Buchhorn
Reiner
R
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000242:Cyclic AMP / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D018377:Neurotransmitter Agents / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D016207:Cytokines; D018377:Neurotransmitter Agents; D000242:Cyclic AMP