Urinary Interleukin-6 Levels Research Articles

Association of urine Interleukin-8 (IL-8) with renal impairment in lupus patients

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with clinical manifestations that vary between individuals with progressive and irreversible SLE organ damage. Recently, it has become known that Interleukin-8 (IL-8) levels in the blood rise in SLE patients compared to healthy people. The increase of IL-8 causes kidney inflammation by promoting the release of the Neutrophil Extracellular Traps (NET) complex, which supports further renal damage. This study aims to evaluate the association of urine interleukin-8 with renal impairment in SLE patients. Methods: A total of 45 lupus participants—22 with and 23 without renal abnormalities—had their urine collected. The interleukin-8 concentration was measured using an enzyme-linked immunosorbent assay (ELISA)—renal impairment criteria based on renal biopsy or ACR 1997 criteria. Mann-Whitney and Spearman correlation tests were employed in the statistical analysis. Data were analyzed using SPSS version 25.0 for Windows. Results: There was no significant difference in IL-8 urine levels between the SLE group with renal impairment (111.27±59.03 pg/ml) and the SLE group without renal impairment (125.76±66.62 pg/ml) was not significant (p=0.67). Urine IL-8 also did not significantly correlate with blood neutrophil count, leukocyte count and leukocyturia (p>0.05). Conclusion: In lupus patients, urine Interleukin-8 levels are not associated with renal impairment.

Fecal and Urinary Adipokines as Disease Biomarkers.

The use of biomarkers is of great clinical value for the diagnosis and prognosis of disease and the assessment of treatment efficacy. In this context, adipokines secreted from adipose tissue are of interest, as their elevated circulating levels are associated with a range of metabolic dysfunctions, inflammation, renal and hepatic diseases and cancers. In addition to serum, adipokines can also be detected in the urine and feces, and current experimental evidence on the analysis of fecal and urinary adipokine levels points to their potential as disease biomarkers. This includes increased urinary adiponectin, lipocalin-2, leptin and interleukin-6 (IL-6) levels in renal diseases and an association of elevated urinary chemerin as well as urinary and fecal lipocalin-2 levels with active inflammatory bowel diseases. Urinary IL-6 levels are also upregulated in rheumatoid arthritis and may become an early marker for kidney transplant rejection, while fecal IL-6 levels are increased in decompensated liver cirrhosis and acute gastroenteritis. In addition, galectin-3 levels in urine and stool may emerge as a biomarker for several cancers. With the analysis of urine and feces from patients being cost-efficient and non-invasive, the identification and utilization of adipokine levels as urinary and fecal biomarkers could become a great advantage for disease diagnosis and predicting treatment outcomes. This review article highlights data on the abundance of selected adipokines in urine and feces, underscoring their potential to serve as diagnostic and prognostic biomarkers.

Elevated Urinary IL-6 Predicts the Progression of IgA Nephropathy

Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. However, biomarkers for predicting the progression or regression of IgAN remain a clinical challenge. In the present study, we aim to identify promising prognostic markers of IgAN. Using the cytokine antibody array, we detected serum and urinary levels of 9 common cytokines selected from 23 IgAN-related biomarkers in 32 patients with IgAN and 16 healthy controls. The best biomarkers for distinguishing IgAN patients from healthy controls were identified and confirmed in a multicenter cohort with 222 patients with IgAN and 159 age- and sex-matched healthy controls. Their associations with IgAN progression were further explored in 762 patients with IgAN with a median follow-up of 65 months. Among the 9 candidate markers, urinary interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) levels were the best for distinguishing patients with IgAN from healthy controls. In the diagnostic cohort, both urinary IL-6 and TGF-β1 levels were elevated in patients with IgAN and showed good discriminatory power, with an area under curve (AUC) of 0.9725 (95% confidence interval: 0.9593-0.9858). Elevated urinary IL-6 level was independently and significantly correlated with the high risk of composite renal outcome (hazard ratio per log-transformed IL-6:1.420 [1.139-1.769]), but no statistical significance was observed between urinary TGF-β1 level and IgAN progression after adjusting for multiple confounders. Elevated urinary IL-6 and TGF-β1 levels predict the progression of IgAN. Urinary IL-6 is an independent risk factor and a promising noninvasive predictor for IgAN progression.

Изменения иммунитета и микроциркуляции в почках на фоне лечения гнойного пиелонефрита

Изменения иммунитета и микроциркуляции в почках на фоне лечения гнойного пиелонефрита

Serum and Urine Interleukin-6 and Interleukin-8 Levels Do Not Differentiate Acute Pyelonephritis from Lower Urinary Tract Infections in Children.

BackgroundUrinary tract infection (UTI) is common in pediatrics. Infection of the upper urinary tract may cause renal scarring, and subsequently renal failure and hypertension. Permanent renal damage has been suggested to be caused by the host inflammatory response. Therefore, it is crucial to understand the host defense mechanisms against such infection in order to make timely diagnosis. The aim of this study was to evaluate interleukin-6 (IL-6) and IL-8 as potential biomarkers in differentiating acute pyelonephritis (AP) from cystitis (Cys) in children.MethodsForty-three children (21 with AP and 22 with Cys) were included. Serum and urinary IL-6 and IL-8 were measured during the acute phase (within 12 hours of presentation) and the convalescent phase (8 weeks post-infection). Thirty-eight healthy children were included as controls.ResultsDuring the acute phase, the mean urinary IL-6 level in the Cys group was significantly higher than that in the controls (17.8 pg/mL vs 14.8 pg/mL, P=0.03), while the serum levels were significantly higher in both the Cys and AP groups than in the controls (19.5 pg/mL, 19.4 pg/mL, 15 pg/mL, P=0.005 and 0.02, respectively). During the convalescent phase, serum and urinary IL-6 levels were higher in patients than in controls. Urinary IL-8 levels were significantly higher in both the AP and Cys groups compared to controls (206.5 pg/mL, 291.8 pg/mL, 89.4 pg/mL, P=0.05 and 0.02, respectively) during the acute phase. Serum IL-8 was not significantly different between the 3 groups. Nonetheless, no significant differences were found between the AP and Cys groups, in urinary or serum levels of IL-6 or IL-8, during both phases.ConclusionIL-6 and IL-8 levels are elevated in patients with UTI. However, the levels did not differentiate between AP and cystitis. Further studies are warranted to evaluate their roles as indicators of the site of UTIs.

Urinary interleukin-6 and tumour necrosis factor-alpha as early markers for diabetic nephropathy in children and adolescents with type 1 diabetes

Background: Diabetic nephropathy (DN) is the main cause of morbidity and mortality in young adults with type 1 diabetes mellitus (T1DM). The accuracy of albuminuria has been frequently questioned as a predictor and prognosticator of renal injury. Therefore, new urinary markers were investigated for the early detection of DN. Objectives: To assess the potential value of urinary interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) as early markers for detection of DN in children and adolescents with T1DM. Method: This case-control study was conducted on 50 children and adolescents with T1DM, aged ≤ 18 years. Patients were classified according to their albumin/creatinine ratio (ACR) into two groups; normo-albuminuric and albuminuric group, together with 25 age and sex-matched healthy controls. ACR, urinary IL-6 and TNF-α levels were assayed for the patients and controls. Results: Urinary interleukin-6/creatinine (IL-6/Cr) ratio of albuminuric patients was significantly higher compared to normo-albuminuric patients or controls. Urinary IL-6/Cr ratio ≥ 0.24 pg/mg showed a significant cutoff value to detect albuminuria with 72% sensitivity and 52% specificity (p= 0.04). While, we did not observe different urinary tumour necrosis factor-alpha/creatinine (TNF-α/Cr) ratio in the studied groups, or between albuminuric and normo-albuminuric patients or controls Conclusions: Urinary IL-6/Cr ratio seems to be a promising new marker for early detection of DN in patients with T1DM, while urinary TNF-α /Cr ratio showed no significant difference between diabetic patients and controls. Sri Lanka Journal of Child Health, 2020; 49(3): 269-275

Promotion of epithelial hyperplasia by interleukin-8-CXCR axis in human prostate.

The clinical manifestation of benign prostatic hyperplasia (BPH) is causally linked to the inflammatory microenvironment and proliferation of epithelial and stromal cells in the prostate transitional zone. The CXC-chemokine interleukin-8 (IL-8) contributes to inflammation. We evaluated the expression of inflammatory cytokines in clinical specimens, primary cultures, and prostatic lineage cell lines. We investigated whether IL-8 via its receptor system (IL-8 axis) promotes BPH. The messenger RNA and protein expression of chemokines, including components of the IL-8 axis, were measured in normal prostate (NP; n = 7) and BPH (n = 21), urine (n = 24) specimens, primary cultures, prostatic lineage epithelial cell lines (NHPrE1, BHPrE1, BPH-1), and normal prostate cells (RWPE-1). The functional role of the IL-8 axis in prostate epithelial cell growth was evaluated by CRISPR/Cas9 gene editing. The effect of a combination with two natural compounds, oleanolic acid (OA) and ursolic acid (UA), was evaluated on the expression of the IL-8 axis and epithelial cell growth. Among the 19 inflammatory chemokines and chemokine receptors we analyzed, levels of IL-8 and its receptors (CXCR1, CXCR2), as well as, of CXCR7, a receptor for CXCL12, were 5- to 25-fold elevated in BPH tissues when compared to NP tissues (P ≤ .001). Urinary IL-8 levels were threefold to sixfold elevated in BPH patients, but not in asymptomatic males and females with lower urinary tract symptoms (P ≤ .004). The expression of the IL-8 axis components was confined to the prostate luminal epithelial cells in both normal and BPH tissues. However, these components were elevated in BPH-1 and primary explant cultures as compared to RWPE-1, NHPrE1, and BHPrE1 cells. Knockout of CXCR7 reduced IL-8, and CXCR1 expression by 4- to 10-fold and caused greater than or equal to 50% growth inhibition in BPH-1 cells. Low-dose OA + UA combination synergistically inhibited the growth of BPH-1 and BPH primary cultures. In the combination, the drug reduction indices for UA and OA were 16.4 and 7852, respectively, demonstrating that the combination was effective in inhibiting BPH-1 growth at significantly reduced doses of UA or OA alone. The IL-8 axis is a promotor of BPH pathogenesis. Low-dose OA + UA combination inhibits BPH cell growth by inducing autophagy and reducing IL-8 axis expression in BPH-epithelial cells.

Blood Neutrophil-to-Lymphocyte Ratio and Urine IL-8 Levels Predict the Type of Bacterial Urinary Tract Infection in Type 2 Diabetes Mellitus Patients.

BackgroundExtended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) are the most common uropathogens causing UTI (urinary tract infection) in type 2 diabetes mellitus (T2DM). Circulatory inflammatory markers such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) are usually dysregulated during UTI. However, the differential regulation of these inflammatory signatures during E. coli and K. pneumoniae UTI in T2DM has not been determined.MethodsA case–control study on 466 patients was performed to investigate the inflammatory signatures indicative of ESBL-E. coli and K. pneumoniae UTIs in T2DM. Serum CRP levels and blood NLR for these patients were determined and associated with E. coli and K. pneumoniae ESBL uropathogen using multivariate logistic regression analysis. Urinary interleukin 8 (IL-8) levels were also assessed and associated with these two UTI uropathogens in T2DM. The association of the two ESBL-uropathogens with the survival outcomes of T2DM patients was also analyzed using Cox-proportional hazard model.ResultsT2DM patients with ESBL-E. coli UTI had lower serum CRP levels (median, CRP mg/dL 33.7 vs 39.8, respectively; P=0.023) and higher blood NLR (median, NLR 3.2 vs 2.6, respectively; P=0.010) compared to those with K. pneumoniae UTIs (P<0.001). Moreover, in T2DM, the urinary IL-8 levels was higher in ESBL-E. coli compared to those with K. pneumoniae UTIs (P<0.0001). After adjusting for confounders, including age, gender, serum albumin, hemoglobulin, leukocytes, and platelet counts, T2DM patients with blood NLR ≥ 3.5 were at higher risk for ESBL-E. coli UTIs than ESBL-K. pneumoniae UTIs (odds ratio [OR], 3.61, 95% confidence interval, Cl, 1.49–8.73; P=0.004). Moreover, T2DM patients with ESBL-E. coli UTIs had higher all-cause mortality (hazard ratio [HR], 4.09; 95%, 1.14–14.59) than those with K. pneumoniae UTIs.ConclusionSerum CRP levels, blood NLR, and IL-8 urinary levels differentiate ESBL-E. coli from K. pneumoniae UTIs in T2DM.

Urinary Interleukin‐6 as biomarker for diagnosis of acute pyelonephritis in children

Introduction Urinary Interleukin-6 (IL-6) a pleiotropic cytokine with pro-inflammatory and immune-regulatory functions is a key mediator of inflammation in children with Urinary tract infection (UTI). Aim of the study The aim of this study is to estimate the role of urinary IL-6 (UIL-6) in diagnosis of acute UTI in children and its usefulness in differentiation between upper urinary tract infection (UUTI) (pyelonephritis) and lower urinary tract infection (LUTI) (cystitis). Patients & Methods This study conducted on a total 56 children divided into 36 patients suffering from UTI with mean age 4.3 ± 3.1 and 20 apparently healthy children age and sex matched with the cases. All patients were subjected to routine investigation and urine IL-6 assay. Results Urinary IL-6 was significantly higher in patients with UTI than control group, Sensitivity was 94.4 %, specificity of 92.1%, positive predictive value was 85%, negative predictive value was 97.2% anddiagnostic accuracy was 92.8% and the best cut off value >17 pg/ml. Also Urinary IL-6 was significantly higher in acute pyelonephritis (APN) in comparison to lower UTI cases and there was a positive correlation between urinary IL-6 level and fever, CRP, and leukocyte count [r = 0.623 P = 0.006, r = 0.816, P < 0.001 and r = 0.688, P < 0.002 respectively] Conclusion Urinary IL-6 level may considered as a reliable biochemical marker to determine the severity of renal injury in APN as well as outcome of pediatric patients

Diagnostic value of urinary interleukin-6 in urinary tract infection in children.

Introduction Urinary tract infection (UTI) is the second most common bacterial infection in children. Aim of the study To estimate the value of urinary Interleukin-6 (IL-6) in diagnosis of UTI in children and also if it can differentiate between upper and lower UTI. Patients and Methods This study included 80 children, divided into 40 patients suffering from UTI and 40 healthy children served as a control group. Patients were classified into acute pyelonephritis (n=22) and lower UTI (n=18). Urine IL-6 was measured by enzyme-linked immune- sorbent assay (ELISA) technique. Results Urinary IL-6 was significantly higher in patients with UTI than control group (p value <0.001) and also it was significantly higher in upper than lower UTI cases (p value <0.001). Conclusion Urinary IL-6 level is a reliable diagnostic tool for early identification of UTI in febrile children. The study confirms usefulness of Urinary IL-6 level is a reliable diagnostic tool for early identification of urinary IL-6 to differentiate between upper and lower UTIs.

Evaluation of liver-type fatty acid binding protein (L-FABP) and interleukin 6 in children with renal cysts.

Renal cysts, according to their etiology, can be divided into genetic and acquired cysts. This is of great importance in patients with cystic kidney disease with a possible poor prognosis to identify markers of early kidney damage. The objective of this study was to evaluate the concentration of serum and urine liver-type fatty acid binding protein (L-FABP) and interleukin 6 (IL-6) in children with kidney cysts. The study was conducted on a group of 39 children with kidney cysts including 20 subjects with autosomal dominant polycystic kidney disease (ADPKD). Serum and urine L-FABP concentration in children with renal cysts was significantly higher compared to the controls, regardless of the underlying type of cystic degeneration, number of cysts and gender. Also, serum and urinary IL-6 concentration was significantly higher than in the control group. There was a significant negative correlation between serum L-FABP concentration and standard deviation score (SDS) for diastolic blood pressure (DBP). A significant negative correlation was found between serum IL-6 concentration and systolic blood pressure (SBP), DBP and mean arterial pressure (MAP) values as well as SDS for SBP and DBP. In addition, a significant positive correlation was found between urinary IL-6 concentration and estimated glomerular filtration rate (eGFR). Higher concentration of L-FABP in serum and urine in children with kidney cysts indicates the early damage to the renal parenchyma, detectable before the onset of hypertension and other organ damage. Significantly higher serum and urinary IL-6 levels in children with cystic kidney disease compared to healthy children may suggest the role of this cytokine in chronic kidney disease development.

Empagliflozin alleviates renal inflammation and oxidative stress in streptozotocin-induced diabetic rats partly by repressing HMGB1-TLR4 receptor axis.

Objective(s):Empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, possesses verified anti-inflammatory and anti-oxidative stress effects against diabetic nephropathy. The present investigation aims to examine empagliflozin effects on the renal levels of high mobility group box-1 (HMGB1), a potent inflammatory cytokine, and its respective receptor toll-like receptor-4 (TLR-4) in STZ-induced diabetic rats.Materials and Methods:Empagliflozin at 10 mg/kg per os (p.o.) was administered for 4 weeks, starting 8 weeks after the induction of diabetes. Renal function, kidney inflammation, oxidative stress, and apoptosis markers as well as renal HMGB1, receptor for advanced glycation end products (RAGE), and TLR-4 levels were assessed.Results:In addition to down-regulating NF-κB activity in renal cortices, empagliflozin reduced renal levels of HMGB1, RAGE, and TLR-4. It alleviated renal inflammation as indicated by diminished renal expressions of inflammatory cytokines and chemokines like tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) and also decreased urinary levels of interleukin-6 (IL-6) and alpha-1 acid glycoprotein (AGP). Moreover, empagliflozin ameliorated renal oxidative stress as demonstrated by decreased renal malondialdehyde (MDA) and elevated renal activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX). It also suppressed renal caspase-3, the marker of apoptosis; and furthermore, enhanced renal function noticed by the declined levels of serum urea and creatinine.Conclusion:These findings underline that empagliflozin is able to attenuate diabetes-related elevations in renal HMGB1 levels, an influential inflammatory cytokine released from the necrotic and activated cells, and its correspondent receptors, i.e., RAGE and TLR-4.

Reduction of renal tubular injury with a RAGE inhibitor FPS-ZM1, valsartan and their combination in streptozotocin-induced diabetes in the rat

Receptor for advanced glycation end-products (RAGE) is involved in the pathogenesis of diabetic nephropathy. FPS-ZM1, a selective RAGE inhibitor, in combination with valsartan were investigated for their protective potentials on the renal markers of tubular injury in streptozotocin-induced diabetic rats. Rats were assigned into groups of receiving FPS-ZM1 (1 mg/kg/day), valsartan (100 mg/kg/day), and FPS-ZM1 plus valsartan (1 mg/kg/day and 100 mg/kg/day, respectively) for one month. Kidney histology, renal inflammation and oxidative stress, and renal and urinary markers of tubular injury were investigated. FPS-ZM1 and valsartan in combination more significantly attenuated renal expressions of tumor necrosis factor-alpha and interleukin-6 genes and reduced urinary levels of interleukin-6. Moreover, the combination elevated renal NAD+/NADH ratios and Sirt1 activities, and mitigated nuclear acetylated NF-κB p65 levels. In addition to alleviating indices of oxidative stress i.e. malondialdehyde, superoxide dismutase and glutathione peroxidase, the combination of FPS-ZM1 and valsartan more effectively upregulated the renal levels of master antioxidant proteins Nrf2, heme oxygenase-1, and NAD(P)H:quinone oxidoreductase-1. Additionally, this dual therapy ameliorated more efficiently the indices of renal tubular injuries as indicated by decreased renal kidney injury molecule-1 levels as well as reduced urinary levels of cystatin C, retinol binding protein, and beta-2-microglobulin. While FPS-ZM1 alone had no appreciable effects on the renal fibrosis, the combination treatment ameliorated fibrosis better than valsartan in the kidneys. Collectively, these findings underline the extra benefits of FPS-ZM1 and valsartan dual administrations in obviating the renal tubular cell injury in streptozotocin-induced diabetic rats partly by suppressing renal inflammation and oxidative stress.

Elevated urinary lipocalin-2, interleukin-6 and monocyte chemoattractant protein-1 levels in children with congenital ureteropelvic junction obstruction

In children with congenital ureteropelvic junction obstruction (UPJO), urinary biomarkers could assist in the diagnosis of renal damage or kidneys at risk for damage. Urinary levels of interleukin-6 (IL6), neutrophil gelatinase-associated lipocalin (LCN2), monocyte chemoattractant protein-1 (MCP1), and transforming growth factor-β1 (TGFB1) proteins have been correlated with renal damage in several contexts. Whether they might be useful non-invasive biomarkers of obstructive nephropathy due to unilateral and bilateral congenital UPJO was tested. A cohort study was performed at People's Hospital of Xinjiang Uygur Autonomous Region in China. Bladder urine samples from 17 patients with UPJO were obtained before surgical intervention and from 17 healthy age-matched controls. Levels of IL6, LCN2, MCP1, and TGFB1 were determined by enzyme-linked immunosorbent assay and normalized to urinary creatinine levels. Levels of urinary LCN2, MCP1, and IL6 were significantly elevated in the urine from individuals with UPJO compared with controls (P=0.0003, P=0.0003, and P=0.0073, respectively). Children with bilateral UPJO (n=5) showed significantly higher levels of IL6, LCN2, and MCP1 protein in their urine compared with controls or those with unilateral UPJO (n=12; P=0.007, P<0.0001, and P=0.0002, respectively). Combining LCN2 and MCP1 slightly improved biomarker performance. Urinary biomarkers could be used in obstructed patients to monitor for renal damage and might find particular utility on patients with bilateral UPJO. Monitoring urinary biomarkers and imaging features in untreated patients could provide insights into the natural history of renal damage due to obstruction and will be necessary to test their performance characteristics as biomarkers. Urinary levels of LCN2 and MCP1 protein are promising biomarkers monitoring children with UPJO, particularly in those with bilateral disease.

Value of urinary levels of interleukin-6, epidermal growth factor, monocyte chemoattractant protein type 1 and transforming growth factor β1 in predicting the extent of fibrosis lesions in kidney biopsies of patients with IgA nephropathy

ObjectiveTo analyse the associations between urinary levels of IL-6 EGF, MCP-1 and TGFβ1 and clinical, biochemical and histopathological characteristics in patients with primary IgA nephropathy and their ability to predict the extent of lesions of glomerular and/or interstitial sclerosis. Patients and methodsA total of 58 patients with IgA nephropathy were studied. We determined the urine levels of IL-6, EGF, MCP-1, and TGFβ1 at the time of diagnosis. The extent of glomerular and interstitial fibrosis was analysed by quantitative morphometry and kidney biopsies were classified according to the Oxford criteria. We analysed the ability of these molecules to predict the extent of glomerular and interstitial fibrosis lesions. ResultsIL-6, TGFβ1 and MCP-1 were associated with focal glomerulosclerosis and interstitial fibrosis extension but not with the presence of mesangial, extracapillary or endocapillary proliferation. EGF showed a negative association with interstitial fibrosis. By categorising patients according to the Oxford classification, patients with T1 and T2 scores had significantly higher levels of IL-6, MCP-1, TGF-β1 and significantly lower levels of EGF than patients with T0 scores. By multiple regression and logistic regression analyses, the levels of MCP-1, IL-6 and EGF were independent predictors of the fibrosis surface, after adjusting for age and eGFR. ConclusionThe urinary concentration of IL-6, EGF and MCP-1 provides additional information that significantly improves the estimation of the surface of interstitial fibrosis in patients with IgA nephropathy.

Inflammation and Cardio-Renal Interactions in Heart Failure: A Potential Role for Interleukin-6

Introduction: Inflammation is considered a key driver of cardio-renal dysfunction in patients with heart failure (HF). Of the myriad of pro-inflammatory cytokines, interleukin 6 (IL-6) is of particular interest; it is a multifunctional effector with a central role in several chronic inflammatory conditions via its influence on ubiquitous cellular pathways. Accordingly, IL-6 has emerged as a promising therapeutic target for several chronic inflammatory states. Whereas IL-6 causes adverse cardio-renal effects in rodent models, its effects on these pathways in humans are less clear. Hypothesis: Plasma and urine IL-6 levels would associate with key parameters of cardio-renal dysfunction such as diuretic resistance, renal filtration, and neurohormonal activation. Methods: We enrolled 98 consecutive patients receiving high-dose loop diuretics in an ambulatory HF unit. IL-6 levels in plasma were used to query systemic inflammation and IL-6 in urine to quantify inflammation at the renal tissue level. Results: Plasma and urine IL-6 levels were modestly correlated (r = 0.40, P < .001), and levels showed varied association with key parameters of cardiorenal syndrome (Fig. 1). Plasma IL-6, a measure of systemic inflammation, showed the strongest relationship with systemic neurohormonal activation (OR for high plasma renin = 1.9 per SD increase, 95% CI 1.2–3.0, P = .008) and risk of mortality (adjusted HR = 2.3 per SD increase, 95% CI = 1.5–3.7, P < .001). Conversely, levels of urine IL-6, which reported on tissue specific inflammation, were closely associated with measures of cardio-renal dysfunction such as diuretic resistance (OR = 2.3 per SD increase, 95% CI 1.4–3.8, P = .001), lower eGFR (OR = 1.9 per SD increase, 95% CI = 1.2–3.1, P = .01) and increased renal tissue-level neurohormonal activation (OR for high urine renin = 2.1 per SD increase, 95% CI 1.3–3.4, P = .002). Conclusion: IL-6 was strongly and independently associated with parameters of cardio-renal dysfunction, neurohormonal activation, and mortality. In the context of existing mechanistic data suggesting a causal role for IL-6 in cardio-renal dysfunction, this pathway represents a potential therapeutic target.

Clinical significance of serum and urinary interleukin-6 in systemic lupus erythematosus patients

BackgroundPrevious studies reported higher interleukin-6 (IL-6) levels in systemic lupus erythematosus (SLE) patients than in healthy controls. However, the clinical relevance of IL-6 in SLE has not been clearly established. Aim of the workThe present study aimed to evaluate the clinical significance of serum and urinary IL-6 and their usefulness as markers of disease activity in SLE. Patients and methods63 SLE patients were included. Disease activity was assessed according to the Systemic Lupus Activity Measure (SLAM) score. Serum and urinary IL-6 were assessed by ELISA. ResultsThe study included 63 Romanian patients, female to male ratio 9.5:1 with a mean age of 45.4±12.6years and disease duration of 8 (3–12.3) years. The median SLAM score at inclusion was 5 (range 3–8). Urinary IL-6 significantly correlated with proteinuria (r=0.25; p=0.04) and negatively with the platelet count, C3 and C4 levels (r=−0.38; p=0.002, r=−0.43; p=0.001, and r=−0.46; p<0.001 respectively). Moreover, in patients with active lupus nephritis (LN), urinary IL-6 correlated with the SLAM (r=0.62; p=0.01). Patients with low urinary IL-6 levels (<7.3pg/ml) had a longer duration of treatment with corticosteroids or hydroxychloroquine (HCQ) (9.5 vs 4years; p=0.02 and 7 vs 4years; p=0.02). In a regression, only C3 was a significant determinant of urinary IL-6 level. ConclusionsUrinary but not serum IL-6 seems to be related to SLE activity in LN patients. Treatment with corticosteroids or HCQ therapy might reduce urinary IL-6 levels in SLE.

Inflammatory Cytokines as Risk Factors for Mortality After Acute Cardiac Events.

Introduction:Inflammatory markers have been identified as potential indicators of future adverse outcome after acute cardiac events.Aim:This study aimed to analyze baseline inflammatory cytokines levels in patients with acute heart failure (AHF) and/or acute coronary syndrome (ACS) according to survival. The main objective was to identify risk factors for mortality after an episode of AHF and/or ACS.Methods:In this prospective longitudinal study 75 patients with the diagnosis of AHF and/or ACS were enrolled. Baseline laboratory and clinical data were retrieved. Serum and urine interleukin-6 (IL-6) and interleukin-18 (IL-18) levels, plasma B-type natriuretic peptide (BNP) and serum cystatin C values were determined. The primary outcome was in-hospital mortality while secondary outcome was six-month mortality.Results:Median serum and urine IL-6 levels, serum and urine IL-18 levels, as well as median concentrations of plasma BNP and serum cystatin C, were significantly increased in deceased in comparison to surviving AHF and/or ACS patients. Univariate Cox regression analysis identified serum IL-6, serum IL-18, urine IL-6, urine IL-18 as well as serum cystatin C and Acute Physiology and Chronic Health Evaluation (APACHE) II score as risk factors for mortality after an episode of AHF and/or ACS. Multivariate Cox regression analysis revealed that only serum IL-6 is the independent risk factor for mortality after acute cardiac events (HR 61.7, 95% CI 2.1-1851.0; p=0.018).Conclusion:Present study demonstrated the strong prognostic value of serum IL-6 in predicting mortality of patients with AHF and/or ACS.

The effect of garlic powder on human urinary cytokine excretion.

To evaluate the effects of orally administered dehydrated garlic powder on cytokine excretion in the urinary tract. A total of 60 healthy volunteers, randomized into 3 groups, were given a single oral dose of 1 g or 3 g of dehydrated garlic powder or placebo. Urine samples were obtained 6.0 and 24.0 h after garlic intake and assayed for interleukin-8 (IL-8), interleukin- 12 (IL-12), tumor necrosis factor-alpha (TNF-α), diallyl disulfide (DADS) and diallyl sulfide (DAS). Significant increases in IL-12 levels over baseline were noted in urine samples obtained after oral intake of 1 g and 3 g of garlic powder (P < .001). In the 1 g and 3 g garlic powder treatment groups, time-dependent variations in IL-12 levels over the study period were significantly different from the placebo group (P < .001). In both garlic treatment groups, urinary levels of IL-8 and TNF-α were not significantly different from baseline and placebo levels (P > .017). DADS and DAS were not detected in the urine samples at any time after garlic powder intake. Oral intake of doses of garlic traditionally used for daily supplementation increases urinary levels of IL-12, which is a potent stimulator of T helper cell 1 (Th-1) immune responses. This observation encourages further studies investigating the immunostimulatory role of garlic in the urinary tract.

Serum and urinary MIP-1α and IP-10 levels in children with urinary tract infections.

Urinary tract infection (UTI) is a common bacterial disease in infants and children, with potentially serious complications, including kidney damage. The aim of this study was to test whether serum and urinary levels of interleukin-6 (IL-6), macrophage inflammatory protein-1a (MIP-1a) and interferon-γ-inducible protein-10 (IP-10) can be used as biomarkers in children with urinary tract infections. The study group consisted of 22 children with UTI and 20 controls. Blood and urine samples were collected in the acute phase and the convalescent phase, on the eighth day after the onset of antibiotic therapy. Serum and urine levels of MIP-1a, IP-10 and IL-6 were measured. In children with UTI in the acute phase, serum MIP-1a and IL-6 levels were significantly higher compared to the controls (p<0.05 and p<0.005, respectively). A correlation between the serum levels of the chemokines MIP-1a and IP-10 in the acute phase was found. The findings suggest that the chemokines MIP-1a or IP-10 respond to infection, but they cannot be used as biomarkers for UTI in childhood.