The activated immune system and the renin-angiotensin-aldosterone system in congestive heart failure.

OBJECTS: The aim of the study was to investigate a possible relationship between plasma renin activity, angiotensin II, serum levels of angiotensin-converting enzyme, aldosterone and markers of immune activation in congestive heart failure (CHF). PATIENTS AND METHODS: Fifty-three patients (50 male, three female, mean age 46 +/- 16 years) with congestive heart failure were studied. Twenty-eight patients had I or II NYHA class of CHF and 25 patients had III or IV NYHA class (NYHA class, mean +/- SD: 2.3 +/- 0.9). Serum neopterin concentration and hormones were measured by commercial radioimmunoassays. Serum soluble receptors of tumour necrosis factor and interleukin-2 were determined by ELISA. RESULTS: All analytes significantly correlated with NYHA classes (P < 0.05). There existed correlations between neopterin and angiotensin-converting enzyme or aldosterone (rs = 0.35 and rs = 0.36, P < 0.05). The soluble tumour necrosis factor receptor concentrations correlated with plasma renin activity (rs = 0.38, P < 0.05). CONCLUSION: The result of our study suggest that there exists some relationship between the renin-angiotensin-aldosterone system and immune activation in severe congestive heart failure, however, the associations found are rather weak.

Stimulated cellular immune system in patients with congestive heart failure.

In this cross-sectional study, we analysed serum concentrations of soluble markers of cellular immune activation, namely, interferon-gamma, neopterin (a product of activated macrophages), soluble interleukin-2 receptor, and soluble CD8, in 25 patients with congestive heart failure. Ten (40%) patients showed increased concentrations (i.e. above the reference ranges of healthy controls) of neopterin, 14 (56%) showed increased soluble interleukin-2 receptor, and 6 (24%) showed increased soluble CD8. Endogenous interferon-gamma was detectable in 10 patients (40%). In addition, we found significant correlations between neopterin and interferon-gamma (rs = 0.417, p < 0.05), and between neopterin and soluble CD8 concentrations (rs = 0.430, p < 0.05). All patients with increased soluble CD8 also had increased soluble interleukin-2 receptor. However, no significant correlations of soluble interleukin-2 receptor with soluble CD8 or any of the other quantities were observed. Increased concentrations of soluble interleukin-2 receptors, soluble CD8 and neopterin indicate that cellular immunity is stimulated in patients with congestive heart failure. Activated CD8-positive T-lymphocytes may represent the source of increased soluble CD8. Endogenous interferon-gamma, which is derived from activated T-cells, may induce neopterin release by monocytes/macrophages.

Patterns of serological markers for cellular immune activation in patients with dilated cardiomyopathy and chronic myocarditis.

We determined serum concentrations of neopterin and beta 2-microglobulin, soluble markers of cellular immune activation, in 27 patients with either dilated cardiomyopathy (DCM) or chronic myocarditis. Neopterin and beta 2-microglobulin concentrations were respectively increased in 2 and 5 of 11 patients with DCM and in 11 and 9 of 16 patients with chronic myocarditis. A higher cardiac functional class (according to the New York Heart Association) was associated with greater neopterin and beta 2-microglobulin concentrations. During follow-up of patients, both neopterin and beta 2-microglobulin concentrations in serum correlated with the course of disease. Additionally, correlations were significant between left ventricular functional tests (end-diastolic volume, end-systolic volume, and ejection fraction) and neopterin and beta 2-microglobulin concentrations. We conclude that measurement of neopterin and beta 2-microglobulin are useful to monitor disease development in patients with myocardial inflammation.