ABSTRACT
UNLABELLED: PURPOSE OR BACKGROUND: Interleukin (IL)-10 is an immunoregulatory cytokine that is produced by a variety of cell types, such as macrophages and activated monocytes. IL-10 possesses numerous anti-inflammatory, anti-thrombotic and anti-atherosclerotic properties. Furthermore, patients with acute coronary syndrome have been demonstrated to have reduced levels of IL-10 compared to their stable counterparts. For these reasons, it has been proposed that IL-10 plays a protective role in both atherogenesis and plaque vulnerability. However, 2 short-term studies on the prognostic utility of IL-10 in patients with acute coronary syndrome have provided conflicting results, with one study showing that reduced levels of IL-10 were predictors of adverse outcomes and another showing that elevated levels predicted poor outcomes. The objective of the present study was to investigate the long-term prognostic significance of baseline IL-10 levels in patients with acute coronary syndrome. METHODS: Baseline plasma IL-10 levels were measured in 193 well-characterized male patients with acute coronary syndrome who were referred for coronary angiography and followed prospectively for 5 years for the development of major adverse cardiovascular events. RESULTS: After controlling for a variety of baseline variables (including established biomarkers such as high-sensitivity C-reactive protein and N-terminal-pro-B-type natriuretic peptide), plasma IL-10 levels (whether analyzed as a continuous variable or as a categorical variable using receiver operating characteristic-derived cut point) were a strong and independent predictor of the composite outcome of death or non-fatal myocardial infarction when using a Cox proportional hazards model. CONCLUSIONS: These data demonstrate that, despite biologic plausibility for IL-10 as being a cardioprotective cytokine, elevated baseline plasma levels of IL-10 are a strong and independent predictor of long-term adverse cardiovascular outcomes in patients with acute coronary syndrome.
Subject(s)
Acute Coronary Syndrome/complications , Acute Coronary Syndrome/mortality , Angina, Unstable/etiology , Interleukin-10/blood , Myocardial Infarction/etiology , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/drug therapy , Aged , Angina, Unstable/blood , Biomarkers/blood , C-Reactive Protein/metabolism , Confounding Factors, Epidemiologic , Hospitals, Veterans/statistics & numerical data , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Myocardial Infarction/blood , Natriuretic Peptide, Brain/blood , New York City/epidemiology , Peptide Fragments/blood , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Prospective Studies , ROC Curve , Risk Assessment , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
Oligomeric ß-amyloid (Aß) has recently been linked to synaptic plasticity deficits, which play a major role in progressive cognitive decline in Alzheimer's disease (AD). Here we present evidence that chronic oral administration of carvedilol, a nonselective ß-adrenergic receptor blocker, significantly attenuates brain oligomeric ß-amyloid content and cognitive deterioration in 2 independent AD mouse models. We found that carvedilol treatment significantly improved neuronal transmission, and that this improvement was associated with the maintenance of number of the less stable "learning" thin spines in the brains of AD mice. Our novel observation that carvedilol interferes with the neuropathologic, biochemical, and electrophysiological mechanisms underlying cognitive deterioration in AD supports the potential development of carvedilol as a treatment for AD.
