Production of interleukin-6, tumor necrosis factor α and interleukin-10 in vitro correlates with the clinical immune defect in chronic hemodialysis patients

Girndt, Matthias; Köhler, Hans; Schiedhelm-Weick, Erika; Schlaak, J. F.; Büschenfelde, Karl‐Hermann Meyer zum; Fleischer, Bernhard

doi:10.1038/ki.1995.70

Cited by 159 publications

(122 citation statements)

References 25 publications

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“…Injury spurs necessary inflammation, regulated by proinflammatory mediators, such as IL-6, which is suppressed by anti-inflammatory forces, such as IL-10. 44,45 This temporal trajectory-of IL-6 functioning before, and eventually spurring, the production of IL-10-may provide perspective and a potential rationale to our findings that IL-6 was more strongly associated with the earlier outcome of AKI in a dose-dependent manner, while IL-10 was more strongly associated with the long-term outcome of mortality. In addition, the proinflammatory functionality of IL-6 lends credibility to the predictive potential of the cytokine to predict AKI, while the anti-inflammatory properties of IL-10 are consistent with the ability of IL-10 levels to predict protection against mortally.…”

Section: Discussionmentioning

confidence: 68%

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

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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

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Section: Discussionmentioning

confidence: 68%

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

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“…Monocytes from CKD patients are preactivated and overproduce proinflammatory cytokines. [54][55][56][57][58] Likewise, T lymphocytes from CKD patients show increased expression of early activation markers and heightened apoptotic turnover. [43][44][45][46][47][48][59][60][61] Of note, data from our control patients indicates a progressive state of monocyte activation over the study period.…”

Section: Effects Of Regular Exercisementioning

confidence: 99%

Evidence for Anti-Inflammatory Effects of Exercise in CKD

Viana

Kosmadakis

Watson

et al. 2014

Journal of the American Society of Nephrology

160

128

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CKD is associated with a complex state of immune dysfunction characterized by immune depression, predisposing patients to infections, and immune activation, resulting in inflammation that associates with higher risk of cardiovascular disease. Physical exercise may enhance immune function and exert antiinflammatory effects, but such effects are unclear in CKD. We investigated the separate effects of acute and regular moderate-intensity aerobic exercise on neutrophil degranulation (elastase release), activation of T lymphocytes (CD69 expression) and monocytes (CD86 and HLA-DR expression), and plasma inflammatory markers (IL-6, IL-10, soluble TNF-receptors, and C-reactive protein) in patients with predialysis CKD. A single 30-minute (acute) bout of walking induced a normal pattern of leukocyte mobilization and had no effect on T-lymphocyte and monocyte activation but improved neutrophil responsiveness to a bacterial challenge in the postexercise period. Furthermore, acute exercise induced a systemic anti-inflammatory environment, evidenced by a marked increase in plasma IL-10 levels (peaked at 1 hour postexercise), that was most likely mediated by increased plasma IL-6 levels (peaked immediately postexercise). Six months of regular walking exercise (30 min/d for 5 times/wk) exerted anti-inflammatory effects (reduction in the ratio of plasma IL-6 to IL-10 levels) and a downregulation of T-lymphocyte and monocyte activation, but it had no effect on circulating immune cell numbers or neutrophil degranulation responses. Renal function, proteinuria, and BP were also unaffected. These findings provide compelling evidence that walking exercise is safe with regard to immune and inflammatory responses and has the potential to be an effective anti-inflammatory therapy in predialysis CKD.

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“…2c, d). a good correlation between reduced proliferation of peripheral blood mononuclear cells, impaired secretion of interleukin-2, and enhanced expression of IL-2 receptor on resting T cells with the clinical sequelae of immunodepression [9]. The response to HBV vaccination in dialysis patients has been regarded as a good predictor of immunocompetence.…”

Section: Resultsmentioning

confidence: 99%

“…In this regard, a defect in the co-stimulatory function of monocytes/macrophages was pathogenetically linked to the uraemic state [l 11. Alternatively, dysregulated production of monocytederived cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and interleukin-1 0 (IL-10) have been implicated in the suboptimal response of HBV vaccination in dialysis patients [9]. High level of IL-6 correlates with impaired immune status, and this defect could be corrected by upregulation of IL-10 secretion in monocytes [9].…”

Section: Significance Of Monocytic Cytokines At Single Cell Level Formentioning

confidence: 99%

“…Alternatively, dysregulated production of monocytederived cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and interleukin-1 0 (IL-10) have been implicated in the suboptimal response of HBV vaccination in dialysis patients [9]. High level of IL-6 correlates with impaired immune status, and this defect could be corrected by upregulation of IL-10 secretion in monocytes [9]. In RTR, alterations of cytokine profile are more complicated as a result of the immunosuppressive therapy.…”

Section: Significance Of Monocytic Cytokines At Single Cell Level Formentioning

confidence: 99%

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Significance of monocytic cytokines at single cell level for the immune responsiveness in renal transplant recipients

Li¹,

Ho²,

Yip³

et al. 2002

Transplant Int

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Cytokine dysregulation is an important factor underlying the immune unresponsiveness to hepatitis B vaccination (HBV) in renal transplant recipients. This study investigated the relationship between monocyte-derived interleukin-6 (IL-6) and interleukin-10 (IL-10) production and the immune responsiveness using flow cytometry (cytoflow) after whole blood culture. According to their previous response to hepatitis B vaccination, 40 renal transplant recipients were divided into two groups of 20 patients. The percentage of CD14+ monocytes stained positive for intracellular IL-6 or IL-10 was measured using flow cytometry after 4 and 20 h of whole blood culture with lipopolysaccharide stimulation. The percentage of CD14 + /IL-6 + cells after incubation in vitro for 4 h was lower in the responders compared to the non-responders and controls (27.15 * 8.93 vs 35.47 * 9.95, P = NS; and 37.06 & 10.89, P < 0.05 respectively).The staining intensity of IL-6 at 4 h for responders was also significantly reduced. At 20 h, there were a significantly higher percentage of CD14+ /IL-lO + positive cells in the responders compared to the non-responders (41.874~ 18.39 vs 27.55 * 17.25, P < 0.05). These results indicate that alteration of intracellular cytokine profile in activated monocytes distinguishes the HBV vaccination responders from the non-responders among renal transplant recipients. The capacity to upregulate monocyte IL-I0 production in this subset of patients may modulate the immune responsiveness and effectively assists in mounting a positive response to HBV vaccination.

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Production of interleukin-6, tumor necrosis factor α and interleukin-10 in vitro correlates with the clinical immune defect in chronic hemodialysis patients

Cited by 159 publications

References 25 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

Evidence for Anti-Inflammatory Effects of Exercise in CKD

Significance of monocytic cytokines at single cell level for the immune responsiveness in renal transplant recipients

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