Effects of darbepoetin-alpha on plasma pro-inflammatory cytokines, anti-inflammatory cytokine interleukin-10 and soluble Fas/Fas ligand system in anemic patients with chronic heart failure

Kourea, Kallirrhoe; Parissis, John; Farmakis, Dimitrios; Panou, Fotios; Paraskevaidis, Ioannis; Venetsanou, Koula; Filippatos, Gerasimos; Kremastinos, Dimitrios Th.

doi:10.1016/j.atherosclerosis.2007.09.039

Cited by 42 publications

(35 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4 Through C-reactive protein screening, we excluded patients with subclinical inflammation; however, all of the cytokines were not measured, and some are known to increase SNS tone during anemia. 26,27 Chronic disease and/or cachexia are also associated with anemia and are known to increase SNS, but the patients in our study did not present these states. 28 Finally, we excluded iron deficiency and drug adverse effects.…”

Section: Discussioncontrasting

confidence: 49%

Tonic Chemoreflex Activation Contributes to Increased Sympathetic Nerve Activity in Heart Failure–Related Anemia

et al. 2010

View full text Add to dashboard Cite

Abstract-Sympathetic activation contributes to both the initiation and progression of heart failure. The role of anemia in determining sympathetic overactivity in chronic heart failure (CHF) patients is unknown. We tested the hypothesis that, in CHF patients, anemia could lead to increased sympathetic activity through tonic activation of excitatory chemoreceptor afferents. We conducted a double-blind, randomized, vehicle-controlled study to examine the effect of chemoreflex deactivation on muscle sympathetic nerve activity in CHF patients with and without anemia. We compared the effect of breathing 100% oxygen for 15 minutes in 18 stable CHF patients with anemia and 18 control CHF patients matched for age, sex, blood pressure, and body mass index. Baseline muscle sympathetic nerve activity was significantly elevated in CHF patients with anemia compared with patients with CHF alone (56.0Ϯ3.2 versus 45.5Ϯ3.1 bursts per minute; PϽ0.0237). Administration of 100% oxygen led to a significant decrease in muscle sympathetic nerve activity in CHF patients with anemia (from 56.0Ϯ3.4 to 50.9Ϯ3.2 bursts per minute; PϽ0.0019). In contrast, neither room air nor 100% oxygen changed muscle sympathetic nerve activity or hemodynamics in patients with CHF alone. We report for the first time direct evidence of increased sympathetic nerve traffic in patients with CHF-related anemia. Sympathetic hyperactivity in patients with CHF and anemia is partially chemoreflex mediated and could explain how anemia contributes to the progression of CHF and increases morbidity and mortality in these patients. (Hypertension. 2010;55:1012-1017.)

show abstract

Section: Discussioncontrasting

confidence: 49%

Tonic Chemoreflex Activation Contributes to Increased Sympathetic Nerve Activity in Heart Failure–Related Anemia

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Furthermore, IL-6 may induce overexpression of hepcidin, an acute-phase protein, with consequent iron metabolism impairment [45]. Other authors observed that administration of exogenous erythropoietin might reduce circulating levels of proinflammatory cytokines and soluble apoptosis mediators [46]. Relative hypoxia associated with lower levels of hemoglobin in CRS type 1 patients may induce mitochondrial and intracellular modifications with consequent cell death throughout necrosis and apoptosis [47].…”

Section: Discussionmentioning

confidence: 99%

Levels of Proinflammatory Cytokines, Oxidative Stress, and Tissue Damage Markers in Patients with Acute Heart Failure with and without Cardiorenal Syndrome Type 1

et al. 2018

View full text Add to dashboard Cite

Background: Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Inflammation and oxidative stress seem to play a pivotal role in its pathophysiology. In this in vivo study, we examined the putative role of inflammation and humoral markers in the pathogenesis of the CRS type 1. Methods: We enrolled 53 patients with acute heart failure (AHF); 17 of them developed AKI (CRS type 1). The cause of AKI was presumed to be related to cardiac dysfunction after having excluded other causes. We assessed the plasma levels of proinflammatory cytokines (TNF-α, IL-6, IL-18, sICAM, RANTES, GMCSF), oxidative stress marker (myeloperoxidase, MPO), brain natriuretic peptide (BNP), and neutrophil gelatinase-associated lipocalin (NGAL) in AHF and CRS type 1 patients. Results: We observed a significant increase in IL-6, IL-18, and MPO levels in CRS type 1 group compared to AHF (p < 0.001). We found higher NGAL at admission in the CRS type 1 group compared to the AHF group (p = 0.008) and a positive correlation between NGAL and IL-6 (Spearman’s rho = 0.45, p = 0.003) and between IL-6 and BNP (Spearman’s rho = 0.43, p = 0.004). We observed lower hemoglobin levels in CRS type 1 patients compared to AHF patients (p < 0.05) and inverse correlation between hemoglobin and cytokines (IL-6: Spearman’s rho = –0.38, p = 0.005; IL-18: Spearman’s rho = –0.32, p = 0.02). Conclusion: Patients affected by CRS type 1 present increased levels of proinflammatory cytokines and oxidative stress markers, increased levels of tissue damage markers, and lower hemoglobin levels. All these factors may be implicated in the pathophysiology of CRS type 1 syndrome.

show abstract

“…EPO, or its derivatives, the longer-acting darbepoetin (DA) or pegylated Mircera along with the addition of either oral or IV iron. Such treatment has been reported in uncontrolled studies [24,25,26,27,28], non-placebo-controlled studies [29,30,31], and small, single-blind [32,33,34,35] and double-blind [36,37], placebo-controlled studies or larger, double-blind, placebo-controlled studies [38,39,40]. The Hb increased by an average of about 2 g/dl with ESA treatment.…”

Section: The Effect Of Correction Of Anemia In Chf Patients Treated Wmentioning

confidence: 99%

“…In addition to the above findings, several of the studies have shown that correction of the anemia with ESA reduced diuretic dose, heart rate, plasma volume, left-ventricular hypertrophy and dilation, pulmonary artery pressure, the severity of mitral regurgitation, and inflammatory factors such as IL-6 and C-reactive protein, and improved renal function, caloric intake, depression, sleep apnea, left-ventricular diastolic function, and the adhesive and proliferative properties of circulating endothelial progenitor cells [24,25,26,27,28,29,30,31,32,33,34,35,36,37]. …”

Section: The Effect Of Correction Of Anemia In Chf Patients Treated Wmentioning

confidence: 99%

The Anemia of Heart Failure

Silverberg¹,

Wexler²,

Palazzuoli³

et al. 2009

Acta Haematol

View full text Add to dashboard Cite

Anemia is common in congestive heart failure (CHF) and is associated with an increased mortality and morbidity. The most likely causes of anemia are chronic kidney disease (CKD) and excessive cytokine production, both of which can cause depression of erythropoietin (EPO) production and bone marrow activity. The cytokines also induce iron deficiency by both reducing gastrointestinal iron absorption and iron release from iron stores located in the macrophages and hepatocytes. Iron deficiency can cause thrombocytosis which might also contribute to cardiovascular complications in both CHF and CKD and is partially reversible with iron treatment. Thus attempts to control this anemia will have to consider both the use of erythropoiesis-stimulating agents (ESA), such as EPO, as well as oral and, probably more importantly, intravenous (IV) iron. The many studies on anemia in CHF patients treated with ESA and oral or IV iron, and even with IV iron without ESA have up to now shown a quite consistent positive effect on hospitalization, fatigue, shortness of breath, quality of life, exercise capacity, and β-natriuretic peptide reduction, in the absence of increased cardiovascular damage related to the therapy. Adequately powered long-term placebo-controlled studies of ESA and/or IV iron are currently being carried out and their results are eagerly awaited.

show abstract

Effects of darbepoetin-alpha on plasma pro-inflammatory cytokines, anti-inflammatory cytokine interleukin-10 and soluble Fas/Fas ligand system in anemic patients with chronic heart failure

Cited by 42 publications

References 32 publications

Tonic Chemoreflex Activation Contributes to Increased Sympathetic Nerve Activity in Heart Failure–Related Anemia

Tonic Chemoreflex Activation Contributes to Increased Sympathetic Nerve Activity in Heart Failure–Related Anemia

Levels of Proinflammatory Cytokines, Oxidative Stress, and Tissue Damage Markers in Patients with Acute Heart Failure with and without Cardiorenal Syndrome Type 1

The Anemia of Heart Failure

Contact Info

Product

Resources

About