Effects of cAMP and β-Adrenergic Receptor Antagonists on the Function of Peripheral T Helper Lymphocytes in Patients with Heart Failure

• Published in: Neuroimmunomodulation 2011-01, Vol.18 (2), p.73-78
• Main Authors: Tian, Xiuqing, Zhang, Lei, Hou, Yinglong, Xu, Wanju, Dong, Yuling, Liu, Jianhua, Liang, Jiangjiu
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - therapeutic use; Adult; Aged; Carbazoles - therapeutic use; Cell Separation; Cyclic AMP - analysis; Cyclic AMP - metabolism; Female; Flow Cytometry; Heart Failure - drug therapy; Heart Failure - immunology; Humans; Interferon-gamma - biosynthesis; Interleukin-10 - biosynthesis; Male; Metoprolol - therapeutic use; Middle Aged; Original Paper; Propanolamines - therapeutic use; Radioimmunoassay; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Helper-Inducer - immunology
• ISSN: 1021-7401; 1423-0216
• DOI: 10.1159/000319375

Objective: To observe the effects of cyclic adenosine monophosphate (cAMP) in peripheral lymphocytes on T helper 1 (TH1)/TH2 cytokine ratios and to investigate the potential impact and mechanism of β-adrenergic receptor antagonists on immune function in patients with chronic heart failure (CHF). Methods: Sixty-nine patients with New York Heart Association functional class II–IV CHF and a radionuclide left ventricular ejection fraction of less than 45% received carvedilol or metoprolol in a randomized fashion. Thirty healthy persons were studied as controls. Interferon (IFN)-γ and interleukin (IL)-10 in CD4+ T lymphocytes were quantified by three-color flow cytometry. cAMP levels in peripheral blood mononuclear cells were tested by radioimmunoassay at baseline and 6 months after treatment. Results: The levels of lymphocyte cAMP in CHF patients were significantly lower than in normal controls (p < 0.01). The IFN-γ/IL-10 ratio was significantly higher in CHF patients (p < 0.01). The levels of cAMP, IFN-γ and IL-10 among CHF patients with different pathogenic factors displayed no significant differences (p > 0.05). The lymphocyte cAMP level was negatively correlated with the IFN-γ/IL-10 ratio (p < 0.01). After treatment with metoprolol and carvedilol, the IFN-γ/IL-10 ratio in the CHF patients was dramatically decreased (p < 0.01 for each drug) and lymphocyte cAMP was remarkably increased (p < 0.01 for each drug). Conclusion: These results suggest that the decrease of cAMP affects the TH1/TH2 phenotype in peripheral lymphocytes of CHF patients. β-Blocking medications appear to have a beneficial effect on the TH1/TH2 balance and on the immune system through increasing production of cAMP, offering further evidence to support the use of β-adrenergic receptor blockers to treat CHF.