Abstract
Objectives: β-Adrenergic receptor agonists such as isoproterenol inhibit production of tumor necrosis factor (TNF)-α in a number of cell types. Because the heart is a source of TNF-α, we hypothesized that isoproterenol would inhibit cardiac production of the cytokine. Design: Analysis of cardiac release of TNF-α. Setting: Medical research laboratory. Subjects: Rats. Interventions: None. Measurements and Main Results: With the approval of the Institutional Animal Care and Use Committee, rats were anesthetized and hearts were removed and perfused. After 30 mins, bacterial lipopolysaccharide (LPS) with or without isoproterenol was infused for 60 mins. At 30, 60, 90, 120, and 150 mins, coronary flow was measured and coronary effluent was analyzed for TNF-α. Cardiac production of TNF-α was expressed as pg/min. Cyclic adenosine monophosphate (AMP) in the coronary effluent was measured. TNF-α messenger RNA was determined in ventricular tissue. After 30 mins, TNF-α was undetectable in the coronary effluent. However, 60 mins after the initiation of LPS infusion, TNF-α release was 875 ± 255 pg/min and increased to 2164 ± 721 pg/min at 150 mins. Simultaneous infusion of isoproterenol with LPS stimulated cyclic AMP release and inhibited TNF-α production. For instance, at 60 and 150 mins, TNF-α release was 75 ± 38 and 58 ± 29 pg/min, respectively (p < .05 vs. LPS alone). Simultaneous infusion of isoproterenol with LPS blocked the induction of TNF-α messenger RNA by LPS. Isoproterenol, begun 30 mins after the initiation of LPS infusion, still suppressed LPS-stimulated TNF-α release by 95% at 150 mins. Similar results were obtained with norepinephrine. Conclusions: Activation of β-adrenergic receptors inhibits cardiac TNF-α release. This implies that cytokine production by the heart is inhibited by the sympathetic nervous system. In heart failure, the cardiac response to the sympathetic nervous system is impaired. This impairment may play a role in the high plasma levels of TNF-α found in heart failure.
Original language | English (US) |
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Pages (from-to) | 3593-3598 |
Number of pages | 6 |
Journal | Critical care medicine |
Volume | 28 |
Issue number | 11 |
DOIs | |
State | Published - Jan 1 2000 |
Externally published | Yes |
Keywords
- Bacterial lipopolysaccharide
- Isolated rat heart
- Isoproterenol
- Messenger RNA
- Norepinephrine
- Tumor necrosis factor-α
- β-Adrenergic receptor
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine