Anti-inflammatory Cytokine Profile in Human Heart Failure

Yamaoka, Makoto; Yamaguchi, Seiji; Okuyama, Masaki; Tomoike, Hitonobu

doi:10.1253/jcj.63.951

Cited by 54 publications

(12 citation statements)

References 39 publications

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“…The beneficial effects of elevated IL-10 plasma levels were restricted to patients with elevated IL-6 and TNF-α plasma levels, which is an indication of an enhanced systemic inflammatory response. These data support the hypothesis that the balance between anti-inflammatory and pro-inflammatory cytokines may reflect the intensity of occult plaque inflammation and vulnerability to rupture [24,25]. Therefore, we examined anti- and pro-inflammatory cytokine ratios and found that IL-10 to IL-6 ratios were strongly associated with AMI.…”

Section: Discussionsupporting

confidence: 77%

Relation of Anti- to Pro-Inflammatory Cytokine Ratios with Acute Myocardial Infarction

Biswas

Ghoshal

Mandal

et al. 2010

Korean J Intern Med

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Background/Aims: Acute myocardial infarction (AMI) is a leading cause of death. Inflammatory processes play an important role in atherosclerosis, which is intimately related to AMI. The aim of this study was to investigate the association between anti-inflammatory and pro-inflammatory cytokines ratios and AMI. Methods: A total of 90 AMI patients and 90 age-and sex-matched controls were recruited in this study. Plasma cytokines and conventional risk factors were determined by standard methods. Results: Patients with AMI showed increased interleukin (IL)-6 and tumor necrosis factor-α levels and lower antito pro-inflammatory cytokine ratios as compared with controls. A multivariate logistic regression analysis revealed that IL-10 to IL-6 ratio was independently associated with the occurrence of AMI (odds ratio [OR], 5.39; 95% confidence interval [CI], 2.39 to 12.17; p < 0.0001). In contrast, IL-6 levels were no longer significant in the multivariate model (OR, 1.02; 95% CI, 0.932 to 1.12; p = 0.603). A receiver operating characteristic (ROC) curve analysis indicated that IL-6 levels and IL-10 to IL-6 ratios were a significant predictor of AMI (area under ROC curve, 0.892 and 0.851, respectively). Conclusions: Our results suggest that the ratio of IL-10 to IL-6 is independently associated with AMI, and reduced levels of this ratio may favor the development of AMI. (Korean J Intern Med 2010;25:44-50)

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Section: Discussionsupporting

confidence: 77%

Relation of Anti- to Pro-Inflammatory Cytokine Ratios with Acute Myocardial Infarction

Biswas

Ghoshal

Mandal

et al. 2010

Korean J Intern Med

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“…A number of investigators have reported elevated levels of these mediators in patients with heart failure. [9][10][11][12] The mechanisms by which these mediators contribute to the pathophysiology of heart failure have not been completely elucidated and are likely to be multifactorial. For example, immunomodulatory mediators may decrease cardiac contractility by means of a number of different mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Immunomodulatory Biomarkers in a Pressure Overload Model of Heart Failure

Bleske¹,

Hwang

Zineh

et al. 2007

Pharmacotherapy

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Study Objectives. To characterize the immunomodulatory response in a pressure overload model of heart failure, and to further validate this animal model of human heart failure. Design. Randomized, controlled, animal study. Setting. Large university research facility. Animals. Twenty-seven, male, Sprague-Dawley rats. Intervention. The rats underwent either aortic constriction or a sham procedure. Measurements and Main Results. Six months after the surgical procedure, echocardiographic measurements were obtained, the animals were sacrificed, and plasma samples were taken to measure concentrations of biomarkers. As six (40%) of the 15 rats in the aortic-constriction group died before the 6 months, only nine rats from this group underwent immunomodulatory evaluation. Compared with the sham procedure, aortic constriction increased the left ventricle:body weight ratio in the rats (p=0.0016) It also decreased the velocity of circumferential shortening (p=0.08) and increased myocardial expression of atrial natriuretic factor, ␤-myosin heavy chain, and fibronectin (p<0.05). Concentrations of the proinflammatory mediator interleukin (IL)-1␤ and the counterregulatory mediator IL-10 also significantly increased (p<0.04) in the group that underwent aortic constriction compared with the group that underwent the sham procedure. Nonsignificant increases (mean change ~50-180%) were also observed for IL-2, IL-6, and leptin concentrations. Conclusions. In this classic animal model of heart failure, a systemic immunomodulatory response was evaluated after 6 months of pressure overload resulting in myocardial decompensation and, in some cases, mortality. The findings are similar to the immunomodulatory response that may be observed in human heart failure. These novel results further define this model of heart failure and suggest another aspect of its relevance to human heart failure with regard to pressure overload and the immunomodulatory response.

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“…Fatigue, depressive symptoms, sleep quality, and cytokines were all analyzed as continuous variables. Similar to others, 30 we examined plasma cytokine levels (picograms/ml [pg/mL]) and also calculated ratios of pro-inflammatory to anti-inflammatory cytokines (TNFα/IL-10 and IL-6/IL-10) because in vivo inflammatory responses are influenced by the balance between pro- and anti-inflammatory molecule levels; 31 these ratios may reflect the degree of systemic inflammation better than concentrations of individual cytokines. Pearson’s correlations were determined, to analyze the relationships between fatigue and other variables.…”

Section: Methodsmentioning

confidence: 99%

Fatigue, Inflammation, and Projected Mortality in Heart Failure

Fink

Gonzalez

Lisowski

et al. 2012

Journal of Cardiac Failure

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Background Fatigue is a prominent and poorly understood symptom of heart failure with reduced ejection fraction (HFrEF). The purpose of this study was to determine whether fatigue correlated with immune biomarkers and prognosis. Methods/Results In patients with HFrEF (N = 59) and healthy controls (N = 25), we prospectively measured fatigue (Profile of Mood States), depressive symptoms (Patient Health Questionnaire-8), sleep quality (Pittsburgh Sleep Quality Index), and immune biomarkers (plasma C-reactive protein [CRP], tumor necrosis factor-α [TNFα], and interleukins [IL-6 and IL-10]). Seattle Heart Failure Model (SHFM) mortality risk scores were determined. Patients with HFrEF had significantly greater fatigue and depressive symptoms and poorer sleep quality compared to control subjects. When controlling for depressive symptoms, however, fatigue did not differ significantly between patients with HFrEF and controls. Patients with HFrEF had significantly lower levels of IL-10 compared to controls. Cytokines did not correlate significantly with fatigue, but fatigue was significantly associated with higher SHFM scores. Conclusions Depressive symptoms were an important covariate of fatigue in patients with HFrEF. Our study findings were the first to show a positive association between fatigue and the SHFM score, indicating that fatigue was associated with poorer prognosis.

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Anti-inflammatory Cytokine Profile in Human Heart Failure

Cited by 54 publications

References 39 publications

Relation of Anti- to Pro-Inflammatory Cytokine Ratios with Acute Myocardial Infarction

Relation of Anti- to Pro-Inflammatory Cytokine Ratios with Acute Myocardial Infarction

Evaluation of Immunomodulatory Biomarkers in a Pressure Overload Model of Heart Failure

Fatigue, Inflammation, and Projected Mortality in Heart Failure

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