Anti-inflammatory interleukin-10 genotype protects dialysis patients from cardiovascular events

Girndt, Matthias; Kaul, Harald; Sester, Urban; Ulrich, Christof; Sester, Martina; Georg, Thomas; Köhler, Hans

doi:10.1046/j.1523-1755.2002.00504.x

Cited by 132 publications

(69 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…IL-6 is appreciated to act more systemically and thus may more accurately reflect circulating levels; however, adipose tissue may contribute a considerable amount of systemic IL-6 and may not completely reflect response to inflammation. 55,56 While we attempted to select prototypical pro-and anti-inflammatory cytokines most relevant to renal abnormality for our study, we ultimately examined only one proinflammatory and one anti-inflammatory biomarker; other investigators have assessed larger panels. Our group traditionally examines biomarkers in relevant pathophysiologic panels and plans to further explore other inflammatory markers in future studies.…”

Section: J Am Soc Nephrol 26: 3123-3132 2015mentioning

confidence: 99%

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Zhang

Garg

Coca

et al. 2015

Journal of the American Society of Nephrology

176

119

View full text Add to dashboard Cite

Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n=960). AKI was defined as a $50% or $0.3-mg/dl increase in serum creatinine from baseline. Pre-and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P=0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes. AKI is a common complication of cardiac surgery, leading to increased morbidity and mortality. 1 Current paradigms of diagnosis and treatment are based on serum creatinine and are thus insensitive. These limitations have spurred the search for novel proteins that are involved in the process of kidney injury. 2,3 While AKI is traditionally recognized and diagnosed by renal functional impairment and structural damage, it is also an inflammatory condition. Understanding and measuring the processes of inflammation in AKI may provide unique tools for its assessment and prediction.To this end, we developed an ancillary study to our large, multicenter cohort study of adult patients

show abstract

Section: J Am Soc Nephrol 26: 3123-3132 2015mentioning

confidence: 99%

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Zhang

Garg

Coca

et al. 2015

Journal of the American Society of Nephrology

176

119

View full text Add to dashboard Cite

show abstract

“…Furthermore, it has been suggested that IL-10 kinetics are different in CKD patients (4). An earlier study showed large interindividual differences in serum IL-10 levels in patients undergoing hemodialysis caused by promoter gene polymorphism (8).…”

Section: Introductionmentioning

confidence: 98%

“…Although Heeschen et al (6) found that higher serum IL-10 levels were related to better clinical outcomes in terms of CV morbidity and mortality among patients with acute coronary syndrome (ACS), Mälarstig et al (7) showed the opposite. Several potential explanations for this discordance have been suggested (8,9). Furthermore, it has been suggested that IL-10 kinetics are different in CKD patients (4).…”

Section: Introductionmentioning

confidence: 99%

The Relationship between IL-10 Levels and Cardiovascular Events in Patients with CKD

Yılmaz

Solak²,

Sağlam

et al. 2014

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Background and objectives Cardiovascular disease is the leading cause of death in patients with CKD. IL-10 is considered an antiatherosclerotic cytokine. However, previous studies have failed to observe an association between IL-10 and cardiovascular disease in CKD. This study aimed to evaluate whether serum IL-10 levels were associated with the risk of cardiovascular events in CKD patients.Design, setting, participants, & measurements Four hundred three patients with stages 1-5 CKD were followed for a mean of 38 (range=2-42) months for fatal and nonfatal cardiovascular events. IL-10 and IL-6 were measured at baseline together with surrogates of endothelial function (flow-mediated dilatation) and proinflammatory markers (high-sensitivity C-reactive protein and pentraxin-3). The association between IL-10 and flow-mediated dilatation through linear regression analyses was evaluated. The association between IL-10 and the risk of cardiovascular events was assessed with Cox regression analysis.Results IL-10, IL-6, high-sensitivity C-reactive protein, and pentraxin-3 levels were higher among participants with lower eGFR. Both fatal (25 of 200 versus 6 of 203 patients) and combined fatal and nonfatal (106 of 200 versus 23 of 203 patients) cardiovascular events were more common in patients with IL-10 concentration above the median. Flow-mediated dilatation was significantly lower in patients with higher serum IL-10 levels, but IL-10 was not associated with flow-mediated dilatation in multivariate analysis. Kaplan-Meier survival curves showed that patients with IL-10 below the median value (,21.5 pg/ml) had higher cumulative survival compared with patients who had IL-10 levels above the median value (log-rank test, P,0.001).Conclusions IL-10 levels increase along with the reduction of kidney function. Higher serum IL-10 levels were associated with the risk of cardiovascular events during follow-up. We speculate that higher IL-10 levels in this context signify an overall proinflammatory milieu.

show abstract

“…High and low IL-10 producers can be distinguished genetically by single nucleotide polymorphisms (SNPs) in the promoter region of the IL-10 gene [23]. In dialysis patients low IL-10 production is associated with increased levels of C-reactive protein [24]. Moreover, a diminished vaccination response against hepatitis B is generally found in low IL-10 producers, and cardiovascular complications occurs significantly more often in this group of dialysis patients.…”

Section: Introductionmentioning

confidence: 99%

Altered CD46-mediated T cell co-stimulation in haemodialysis patients

Brinkkoetter

Marinaki

Göttmann

et al. 2005

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummaryWhile most of our understanding of immune dysfunction in dialysis patients involves alterations in CD28-CD80/86 signalling, nothing is known of CD46-mediated co-stimulation of T cells in these patients. Because C3b/C4b bind to CD46 and complement activation occurs during haemodialysis (HD), we addressed whether CD46-mediated T cell activation is altered in HD ( n = 9), peritoneal dialysis (PD) ( n = 10) and predialysis patients ( n = 8) compared to healthy controls (HC) ( n = 8). T cell surface markers, T cell proliferation and interleukin (IL)-10 production were studied in CD4 + T cells. In addition, CD46 splice-variants and IL-10 promoter gene polymorphisms were studied by reverse transcription (RT) or amplification refractory mutation systempolymerase chain reaction (ARMS-PCR), respectively. In all uraemic patients, irrespective of the stage of renal insufficiency or dialysis modality, a significant increase in the percentage of CD25 positivity in naive CD4 + T cells was found (64% ± ± ± ± 21% versus 23% ± ± ± ± 18%, P < < < < 0·001). Lymphocytes of HD patients proliferated in greater numbers and produced more IL-10 after costimulation with anti-CD46 than after co-stimulation with anti-CD28. This was also found in CD4 + T cells of PD patients, albeit to a lesser extent. In contrast, with T cells of predialysis patients and of HC, co-stimulation via CD28 was more efficient. The observed alterations in T cell proliferation and IL-10 production were associated neither with CD46 splice variants nor with IL-10 promoter gene polymorphisms. Lymphocytes of HD patients show an increased response on CD46 co-stimulation. These data suggest that ongoing complement activation in HD patients may lead to alterations in acquired immunity.

show abstract

Anti-inflammatory interleukin-10 genotype protects dialysis patients from cardiovascular events

Abstract: The IL-10 genotype influences the risk for cardiovascular events in hemodialysis patients and allows the definition of a high risk group. The data provide further evidence for a causal role of systemic inflammation for progressive atherosclerosis in dialysis patients.

Cited by 132 publications

References 20 publications

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

The Relationship between IL-10 Levels and Cardiovascular Events in Patients with CKD

Altered CD46-mediated T cell co-stimulation in haemodialysis patients

Contact Info

Product

Resources

About