Key Points
- To determine the regulatory effects of adenosine and specific adenosine receptor subtypes on TNF-alpha and IL-6 expression in cardiac tissue.
- Measured cytokine mRNA and protein release in cultured rat cardiomyocytes exposed to adenosine and selective A1, A2, and A3 receptor agonists and antagonists.
- Assessed cytokine mRNA changes and immunolocalization in trabecular muscle specimens obtained from patients with cardiomyopathy.
- In rat cardiomyocytes, adenosine suppressed TNF-alpha mRNA by 40% (P < 0.05) via A2 receptor activation and increased IL-6 mRNA 4.7-fold (P < 0.05) with a twofold increase in IL-6 protein release (P < 0.001) via A3 receptor activation.
- In human trabecular muscles, an A2 agonist suppressed TNF-alpha mRNA by 60% (P < 0.05), but adenosine did not alter IL-6 expression.
- In the failing human heart, IL-6 expression was immunolocalized specifically to infiltrating inflammatory cells rather than cardiac muscle cells.
Structured PICO
PPopulationRat cardiomyocytes and trabecular muscles obtained from patients with cardiomyopathy
IInterventionAdenosine and specific adenosine receptor agonists/antagonists (A1, A2, A3)
CComparatorUntreated control (implied)
OOutcomeExpression of TNF-alpha and IL-6 mRNA and protein releasesurrogate
Adenosine differentially regulates cardiac expression of TNF-alpha and IL-6 via A2 and A3 receptors, with distinct responses observed between rat cardiomyocytes and failing human hearts.