interleukin-8 and Kidney-Diseases

Inflammatory cytokines are important predictors of cardiovascular mortality especially in patients with chronic kidney disease. Here we explored the relationship of anemia and epoetin treatment to inflammatory cytokine levels in patients with chronic kidney disease. One hundred non-dialysis patients with chronic kidney disease over 18 years of age were evenly split into anemic and non-anemic cohorts. Of the 50 anemic patients, 23 were receiving erythropoiesis stimulating agents treatments. Levels of tumor necrosis factor (TNF)-alpha were found to be significantly higher and serum albumin was significantly lower with trends towards higher interleukin (IL)-6 and IL-8 in anemic compared to non-anemic patients. Further analysis by multiple logistic regression found that anemic patients treated with erythropoiesis stimulating agents had significantly higher odds for the upper two quartiles for IL-6, IL-8 and TNF-alpha compared to non-anemic patients. Our study found that the anemia of chronic kidney disease was associated with up regulation of TNF-alpha, and possibly IL-6 and IL-8 along with increased levels of these proinflammatory cytokines in patients treated with epoetin.

Topics: Aged; Anemia; Biomarkers; Case-Control Studies; Chronic Disease; Cytokines; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Inflammation; Interleukin-6; Interleukin-8; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Tumor Necrosis Factor-alpha; Up-Regulation

Cardiopulmonary bypass (CPB) induces an inflammatory response believed to contribute to postoperative morbidity. We hypothesized that the magnitude of the inflammatory response following CPB would be associated with adverse clinical outcomes.. Twenty-nine patients had plasma TNF, IL-6, IL-8, elastase, histamine, complement C5a, and complement C3a measured by ELISA before, during, and after cardiac operations employing CPB. Inflammatory mediator levels were analyzed with respect to outcomes.. Mediator levels peaked at 4 h post-CPB and either returned to baseline or substantially decreased by 24 h. Patients with peak mediator levels above the median for the group as a whole were classified as 'hyper-responders'; those with levels below the median were classified as 'normal responders'. While IL-8, C3a, and IL-6 levels were independently associated with adverse outcomes, TNF, histamine, and C5a levels were not. Elastase levels trended towards adverse outcomes. IL-8 'hyper-responders' experienced significantly greater postoperative weight gain and had higher IL-8 levels at 24 h (p<0.05), with trends towards renal impairment and protracted supplemental oxygen requirements. C3a 'hyper-responders' strongly trended towards increased bleeding, delayed extubation, greater postoperative weight gain, and decreased levels of independent functioning at discharge (p < or = 0.10). IL-6 'hyper-responders' experienced significantly more postoperative bleeding, delayed extubation, and higher IL-6 levels at 24 h compared to 'normal responders' (p < 0.05). They strongly trended towards greater postoperative weight gain and decreased levels of independent functioning at discharge (p < or = 0.10).. Patients who have an exaggerated inflammatory response to CPB tend to bleed more, require more respiratory support, demonstrate greater capillary leak via weight gain, and display a decline in independent functioning relative to normal responders. Thus, it appears that the magnitude of the inflammatory response to CPB adversely influences clinical outcomes.

Topics: Aged; Biomarkers; Cardiopulmonary Bypass; Complement C3a; Enzyme-Linked Immunosorbent Assay; Female; Heart Diseases; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Interleukin-8; Kidney Diseases; Lung Diseases; Male; Middle Aged; Pancreatic Elastase; Postoperative Complications; Treatment Outcome

A total of 105 patients participated in this study, including 10 with chronic glomerulonephritis with normal renal function (CGN patients), 36 uraemic patients (CRF patients), 19 continuous ambulatory peritoneal dialysis patients (CAPD) without peritonitis, three CAPD patients with peritonitis, 37 patients undergoing chronic haemodialysis (HD) divided into short-term HD, 15 patients; medium-term HD, 12 patients; and long-term HD, 10 patients. IL-8 and two other proinflammatory cytokines, IL-6 and TNF alpha were tested using a specific immunoassay. IL-8, IL-6, and TNF alpha serum levels were significantly increased in patients with chronic renal failure compared to their levels in normal individuals (P < 0.0001, P < 0.05 and P < 0.0001 respectively). The most pronounced increment in IL-8, IL-6 and TNF alpha serum levels was observed in CAPD patients (P < 0.0001). CAPD patients without peritonitis showed relatively low levels of IL-8 or IL-6 in peritoneal dialysate effluents (PDE), whereas PDE-TNF alpha were not detectable in almost all patients tested. Patients with peritonitis showed very high serum and PDE levels of IL-8, IL-6 and TNF alpha. The clinical recovery from peritonitis was characterized by a rapid fall in IL-8, IL-6 and TNF alpha in serum and dialysate. HD patients showed a significant increase in serum levels of IL-8 and also IL-6 and TNF alpha compared to normal individuals (P < 0.05, P < 0.05 and P < 0.01 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Chronic Disease; Female; Glomerulonephritis; Humans; Interleukin-6; Interleukin-8; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Renal Dialysis; Renal Replacement Therapy; Tumor Necrosis Factor-alpha; Uremia

The damage to small vessels in AAV and inflammatory reactions are accompanied by the release of various chemokines and cytokines. Using a flow cytometry technique, we assessed the levels of specific cytokines, namely IL-1β IL-6, IL-8, IL-10, IL12p70, and TNF, and chemokines, IFN-α, IP-10, and MIG in the serum from 9 healthy volunteers and 20 AAV patients, where 11 of the patients were not treated and evaluated at the time of diagnosis and 9 were already diagnosed and taking CY + GCS. The obtained results were then compared considering the activity of the disease, the type and titre of the ANCA antibodies, the inflammatory status, and the kidneys' condition. Amongst others, the IL-6, IL-8, IL-10, TNF, and MIG levels were much higher in the serum of AAV patients than in healthy controls, whereas the level of IL-1β was higher in healthy volunteers. Additionally, the levels of IL-6, IL-10, IP-10, and MIG negatively correlated with the eGFR level, while the level of IFN-α positively correlated with the titre of PR3-ANCA. As most of the molecules are implicated in trafficking primed neutrophils towards small vessels, looking for links between the levels of these cytokines/chemokines and the clinical symptoms of AAV may facilitate the diagnosis and predict the progression of the disease.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Chemokine CXCL10; Cytokines; Humans; Interferon-alpha; Interleukin-10; Interleukin-6; Interleukin-8; Kidney Diseases

Sickle cell anemia (SCA) is an important cause of chronic kidney disease, but its pathophysiology is not completely understood. The aim of this study was to compare inflammatory biomarkers in urine samples of SCA children with and without albuminuria, and to explore correlations with renin-angiotensin system (RAS) molecules. A cross-sectional study of 213 children selected from the Minas Gerais state cohort were assigned to two groups: Group 1-89 children with SCA who had albuminuria; Group 2-124 children with SCA and normal albuminuria matched by age and sex with group 1. A subset of 89 children was prospectively followed for a median time of 1.1 year. Inflammatory biomarkers (chemokines and cytokines) in urine were measured using cytometric beads array, and RAS molecules were measured by ELISA. Children with albuminuria had significantly higher urinary levels of IP-10/CXCL10, MCP-1/CCL2, MIG/CXCL9, IL-8/CXCL8, IL-12p70, TNF, IL-10, and IL-6 than patients with normal albuminuria. In the correlation analysis, albumin/creatinine ratio was significantly and positively correlated with IP-10/CXCL10, MCP-1/CCL2, MIG/CXCL9, IL-8/CXCL8, TNF, IL-10, and IL-6. Significant correlations were found between inflammatory and RAS molecules. In the prospective analysis, cumulative risk of persistent albuminuria was higher for children with urinary levels of IP-10/CXCL10 or IL-6 above the 50th percentile. Our data showed that inflammatory markers and RAS molecules might contribute to the occurrence of albuminuria in children with SCA, suggesting that both pathways interact in sickle cell nephropathy.

Topics: Adolescent; Albuminuria; Anemia, Sickle Cell; Biomarkers; Chemokine CCL2; Chemokine CXCL10; Chemokine CXCL9; Chemokines; Child; Child, Preschool; Cross-Sectional Studies; Cytokines; Female; Follow-Up Studies; Humans; Infant; Inflammation; Interleukin-10; Interleukin-12; Interleukin-6; Interleukin-8; Kidney Diseases; Male; Prospective Studies; Renin-Angiotensin System; Tumor Necrosis Factor-alpha; Young Adult

Topics: Aged; APACHE; Cardiovascular Diseases; Cohort Studies; Critical Illness; Disseminated Intravascular Coagulation; Extracellular Traps; Female; Gastrointestinal Diseases; Humans; Intensive Care Units; Interleukin-8; Kidney Diseases; Male; Middle Aged; Mitogen-Activated Protein Kinases; Mortality; Multivariate Analysis; Nervous System Diseases; Neutrophils; Organ Dysfunction Scores; Prospective Studies; Reproducibility of Results; Respiratory Tract Diseases; Risk Assessment; Sepsis; Wounds and Injuries

The prevalence of gout is relatively high worldwide, and many gout patients suffer from uric acid nephropathy (UAN) concomitantly. ELR-CXC chemokines such as CXCL8 and CXCL1 have a elevated expression in UAN. In this research, a mouse UAN model was established for a 12 week duration, and uric acid-related crystals were observed. CXCL8(3-72)K11R/G31P (G31P) is a mutant protein of CXCL8/interleukin 8 (IL-8), which has been reported to have therapeutic efficacy in both inflammatory diseases and malignancies for it acts as a selective antagonist towards CXCR1/CXCR2. In this study, G31P-treated mice showed declined production of the blood urea nitrogen (BUN) level and urine volume in UAN mice compared with G31P-untreated UAN counterparts. In addition, G31P effectively improved renal fibrosis, and reduced uric acid accumulation and leukocyte infiltration in UAN kidneys. Furthermore, the expressions of CXCL1 and CXCL2 were reduced and the activation of NOD-like receptors protein 3 (NLRP3) was inhibited by G31P treatment. This study has demonstrated that G31P attenuates inflammatory progression in chronic UAN, and plays a renoprotective function.

Topics: Animals; Blood Urea Nitrogen; Chemokine CXCL1; Disease Models, Animal; Humans; Interleukin-8; Kidney Diseases; Leukocytes; Male; Mice; Nephritis; NLR Family, Pyrin Domain-Containing 3 Protein; Peptide Fragments; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Uric Acid

Cisplatin (DDP), a cytotoxic antitumor drug, functions in a dose-dependent manner. However, the pursuit for high‑dose therapeutic effects leads to more serious side effects including kidney toxicity. Nephrotoxicity caused due to endothelial cell dysfunction and neutrophils infiltration in kidneys. Interleukin-8 (IL-8) is an ELR+ chemokine binds with CXCR1/2 receptors and its role is primarily in neutrophils recruitment and also involved in invasion, angiogenesis and metastasis of different solid tumors including liver cancer. G31P, a CXCR1/2 antagonist, binds with CXCR1/2 with high affinity, and acts as an anti-inflammatory and antitumor agent. In the present study, we examined the antitumor effects of G31P and DDP on mouse liver cancer cells, and the effects exerted by G31P on cisplatin-induced renal injury. In vitro, effects of the G31P and DDP regimen on H22 cell proliferation were investigated by MTT assay. In vivo BALB/c mice were inoculated subcutaneously with 1x106 H22 cells and treated after one week with a high single dose of DDP with and without G31P on alternative days until the experiment was terminated. On the 15th day the mice were sacrificed, dissected and kidney tissues were analyzed using H&E staining. Myeloperoxidase (MPO) activity was assessed and RT-PCR was performed to detect inflammatory cytokines. Solid tumors were weighed for tumor growth and performed pathological examination, immunohistochemistry and western blotting were performed to detect tissue-related protein expressions in tumor tissue. The tumor inhibitory rate of DDP, G31P and DDP+G31P groups was 38.40, 40.74 and 74.80%, respectively, and the general state of mice in the DDP+G31P group was significantly improved as compared to the DDP group. The results indicated that G31P with DDP significantly inhibited the proliferation while the growth of H22 cell carnimona in vitro and in vivo enhanced the efficacy of cisplatin in cancer treatment with reduced side effects on acute renal failure.

Topics: Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Line, Tumor; Cisplatin; Cytokines; Cytoprotection; Drug Synergism; Female; Interleukin-8; Kidney Diseases; Liver Neoplasms; Mice; Mice, Inbred BALB C; Peptide Fragments

Higher plasma concentrations of inflammatory and apoptosis markers in critically ill patients receiving RRT are associated with RRT dependence and death. This study objective was to examine whether plasma inflammatory (IL-6, -8, -10, and -18; macrophage migration inhibitory factor) and apoptosis (death receptor-5, tumor necrosis factor receptor I and II) biomarkers augment risk prediction of renal recovery and mortality compared with clinical models.. The Biologic Markers of Recovery for the Kidney study (n=817) was a prospective, nested, observational cohort study conducted as an ancillary to the Veterans Affairs/National Institutes of Health Acute renal failure Trial Network study, a randomized trial of intensive versus less intensive RRT in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 Veterans Affairs- and university-affiliated centers. Primary outcomes of interest were renal recovery and mortality at day 60.. A parsimonious clinical model consisting of only four variables (age, mean arterial pressure, mechanical ventilation, and bilirubin) predicted renal recovery (area under the receiver-operating characteristic curve [AUROC], 0.73; 95% confidence interval [95% CI], 0.68 to 0.78) and mortality (AUROC, 0.74; 95% CI, 0.69 to 0.78). By contrast, individual biomarkers were only modestly predictive of renal recovery (AUROC range, 0.55-0.63) and mortality (AUROC range, 0.54-0.68). Adding plasma IL-8 to a parsimonious model augmented prediction of recovery (AUROC, 0.76; 95% CI, 0.71 to 0.81; P=0.04) and mortality (AUROC, 0.78; 95% CI, 0.73 to 0.82; P<0.01) compared with the clinical model alone.. This study suggests that a simple four-variable clinical model with plasma IL-8 had predictive value for renal recovery and mortality. These findings require external validation but could easily be used by clinicians.

Topics: Age Factors; Apoptosis Regulatory Proteins; Area Under Curve; Arterial Pressure; Bilirubin; Biomarkers; Critical Illness; Humans; Inflammation Mediators; Interleukin-8; Kidney; Kidney Diseases; Models, Biological; Predictive Value of Tests; Prospective Studies; Recovery of Function; Renal Replacement Therapy; Respiration, Artificial; Risk Assessment; Risk Factors; ROC Curve; Time Factors; Treatment Outcome; United States; United States Department of Veterans Affairs

Drug-induced nephrotoxicity causes acute kidney injury and chronic kidney diseases, and is a major reason for late-stage failures in the clinical trials of new drugs. Therefore, early, pre-clinical prediction of nephrotoxicity could help to prioritize drug candidates for further evaluations, and increase the success rates of clinical trials. Recently, an in vitro model for predicting renal-proximal-tubular-cell (PTC) toxicity based on the expression levels of two inflammatory markers, interleukin (IL)-6 and -8, has been described. However, this and other existing models usually use linear and manually determined thresholds to predict nephrotoxicity. Automated machine learning algorithms may improve these models, and produce more accurate and unbiased predictions.. Here, we report a systematic comparison of the performances of four supervised classifiers, namely random forest, support vector machine, k-nearest-neighbor and naive Bayes classifiers, in predicting PTC toxicity based on IL-6 and -8 expression levels. Using a dataset of human primary PTCs treated with 41 well-characterized compounds that are toxic or not toxic to PTC, we found that random forest classifiers have the highest cross-validated classification performance (mean balanced accuracy = 87.8%, sensitivity = 89.4%, and specificity = 85.9%). Furthermore, we also found that IL-8 is more predictive than IL-6, but a combination of both markers gives higher classification accuracy. Finally, we also show that random forest classifiers trained automatically on the whole dataset have higher mean balanced accuracy than a previous threshold-based classifier constructed for the same dataset (99.3% vs. 80.7%).. Our results suggest that a random forest classifier can be used to automatically predict drug-induced PTC toxicity based on the expression levels of IL-6 and -8.

Topics: Algorithms; Artificial Intelligence; Bayes Theorem; Humans; Interleukin-6; Interleukin-8; Kidney Diseases; Kidney Tubules, Proximal; Models, Theoretical; Pharmaceutical Preparations; ROC Curve; Support Vector Machine

To investigate the effect of continuous renal replacement therapy (CRRT) on the outcome of severe pneumonia in patients receiving long-term immunosuppressants.. Thirty-four patients, who had been treated with long-term immunosuppressants, were admitted for severe pneumonia. After admission, the dose of immunosuppressants including glucocorticoids was decreased, and the patients were divided into 2 groups: antibiotic treatment group (n = 16) and antibiotic + CRRT treatment group (n = 18). Before and after treatment, the changes of the patients' condition, chest CT and blood gas analysis were monitored. Biomarkers including C-reactive protein (CRP), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8(IL-8), white blood cell and neutrophil counts were determined.. After treatment, the levels of CRP[(109 ± 24) vs (40 ± 13) mg/L], IFN-γ [(151 ± 28) vs (42 ± 12) ng/L], TNF-α [(301 ± 45) vs (118 ± 28) pg/L], IL-6 [(214 ± 45) vs (76 ± 23) pg/L], IL-8[(590 ± 121) vs (159 ± 60) pg/L], white blood cell count [(14.3 ± 5.7)×10⁹/L vs (8.5 ± 2.7)×10⁹/L], and neutrophil percentage [(91.3 ± 3.1)% vs (75.3 ± 2.6)%] decreased significantly in the antibiotic + CRRT group (P < 0.05) as compared to the antibiotic treatment group. In the antibiotic + CRRT group, blood gas showed significant improvement in pH [(7.30 ± 0.12) to (7.37 ± 0.18)], SaO₂ [(80.6 ± 7.6)% to (91.9 ± 7.3)%] and PaO₂ (41 ± 6) mm Hg (1 mm Hg = 0.133 kPa) to (71 ± 9) mm Hg. The patients' condition and chest CT abnormalities also improved more rapidly in the antibiotic + CRRT group. The 6-month survival was increased by 12.9% in the antibiotic + CRRT group as compared to the antibiotic group (P < 0.05).. CRRT is effective in clearance of inflammatory mediators and may increase survival of severe pneumonia patients receiving long-term treatment of immunosuppressants.

Topics: Adult; Aged; Anti-Bacterial Agents; C-Reactive Protein; Female; Glucocorticoids; Hemofiltration; Humans; Immunosuppressive Agents; Interferon-gamma; Interleukin-6; Interleukin-8; Kidney Diseases; Lung; Male; Middle Aged; Pneumonia; Prognosis; Radiography; Renal Replacement Therapy; Retrospective Studies; Treatment Outcome; Tumor Necrosis Factor-alpha

Acute pyelonephritis (APN) is one of the most significant bacterial infections in infancy and early childhood, and can lead to permanent kidney damage and chronic renal failure.. To evaluate interleukin-6 (IL-6) and interleukin-8 (IL-8) levels in the urine of children with renal scarring (RS), searching for clinical information about the immuno-inflammatory process that contributes to RS.. Urine concentrations of IL-6 and IL-8 were evaluated in 50 children, 33 with RS detected after an episode of acute pyelonephritis (group A) and 17 children with a history of acute pyelonephritis, but without RS (group B). These children were divided into four groups: group A(1), 23 children with RS and vesicoureteral reflux (VUR); group A(2), 10 children with RS without VUR; group B(1), 13 children without RS and without VUR; group B(2), 4 children without RS, but with VUR. None of them had had urinary tract infection for a minimum of 6 months. To avoid dilution effects, urinary levels of IL-6 and IL-8 were expressed as the ratio of cytokine to urinary creatinine (pg/mg).. Urinary IL-8 levels were below the lower detection limit in all samples. IL-6 was detectable in the majority of children with RS and below the detection limits in the urine samples of children without RS. There were no statistically significant differences between urinary interleukin-6 levels in children with and those without VUR. There was a significant relationship between the grade of renal scars, the time passed since the last episode of acute pyelonephritis and the urinary levels of IL-6 (p < 0.0001 and p < 0.04 respectively).. Further experimental studies are required to demonstrate the correlation between histopathology and urinary cytokine levels.

Topics: Child; Child, Preschool; Cicatrix; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant; Interleukin-6; Interleukin-8; Kidney Diseases; Male; Pyelonephritis; Vesico-Ureteral Reflux

The objective of this study was to assess the urine levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) as noninvasive markers of vesicoureteral reflux (VUR) and renal parenchymal scarring (RPS) in children in the absence of a recent urinary tract infection (UTI) episode. Urine concentrations of IL-6 and IL-8 in 114 children aged 1 month to 16 years were evaluated. The children were divided into four groups: group 1, 26 children with VUR and RPS; group 2, 27 children with VUR without RPS; group 3, 34 children with RPS without VUR, group 4, 27 children without VUR and RPS, as the control group. After the first assessment, the children were divided into four larger groups for comparison purposes: group A (groups 1+2), 53 children with VUR; group B (groups 3+4), 61 children without VUR; group C (groups 1+3), 60 children with RPS; group D (groups 2+4), 54 children without RPS. Urinary IL-6 and IL-8 concentrations were determined. To avoid dilution effects and to the standardize samples, urinary levels of IL-6 and IL-8 were expressed as the ratio of cytokine to urinary creatinine (pg/mg). The median urine IL-6/creatinine was significantly higher in patients with VUR than in those without VUR (5.72 vs. 3.73). In patients with VUR, there was a significant but rather weak correlation between IL-6/creatinine concentrations and there flux grade (p<0.05, R=0.305). The median urine IL-8/creatinine was significantly higher in patients with RPS than in those without RPS (43.12 vs. 16.36). In patients with RPS, there was a significant but rather weak correlation between IL-8/creatinine concentrations and the renal scar grade (p<0.05, R=0.251). The results of this study provide preliminary evidence that children with VUR have a high urine IL-6 concentration, whereas children with RPS have a high urine IL-8 concentration.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Cicatrix; Creatinine; Female; Humans; Infant; Interleukin-6; Interleukin-8; Kidney; Kidney Diseases; Male; Predictive Value of Tests; Prospective Studies; ROC Curve; Severity of Illness Index; Up-Regulation; Vesico-Ureteral Reflux

Toll-like receptors (TLRs) are an evolutionarily conserved family of cell membrane receptors that are part of the innate immunity system playing an important role as a first response to tissue injury. TLR2 and TLR4 are constitutively expressed on renal epithelium, and their expression is enhanced following renal ischemia/reperfusion (I/R) injury. Genetic deletion of either TLR2 or TLR4 protects from renal I/R injury. However, it is not known whether deletion of both combined protects the kidney more than a deletion of either one alone. Therefore, we performed renal I/R injury in mice lacking TLR2, TLR4, and TLR2/4, respectively. Our results demonstrate that there are no significant differences regarding protection from renal I/R injury in TLR2/4((-/-)) compared with either TLR2((-/-)) or TLR4((-/-)) gene-targeted mice as determined by histological evaluation and renal functional parameters. Furthermore, there was no difference in the number of apoptotic tubular cells and in nuclear translocation of nuclear factor kappa-B (NF-kappaB) between the TLR-gene-targeted groups. In parallel, in vitro experiments did not demonstrate an additional effect of the double genetic deletion compared with the single gene deletion with respect to tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 production in hypoxic isolated proximal tubular epithelial cells of the respective animals. In conclusion, a double genetic deletion of TLR2 and TLR4 confers a similar protection following renal I/R injury compared with single deletions of TLR2 and TLR4.

Topics: Animals; Apoptosis; Cells, Cultured; Disease Models, Animal; Immunity, Innate; Interleukin-8; Kidney; Kidney Diseases; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B; Reperfusion Injury; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Vesico-ureteral reflux (VUR) is the most common inherited disorder of the lower urinary tract. Children with VUR are at risk for ongoing renal damage with subsequent infections. IL8 is an important inflammatory mediator which can be produced by epithelial cells of the renal tract in response to a variety of inflammatory stimuli. High serum concentrations of IL-8 have been reported in patients with chronic renal failure. Elevated IL-8 levels have been reported in the urine of patients with VUR and renal parenchymal scarring (RPS). More recently it was reported that urine IL-8 levels remain elevated in infants with VUR even in the absence of a urinary tract infection (UTI). Increased IL-8 expression has been shown to be associated with polymorphism at position -251 (rs4073) of the IL-8 promoter. The aim of this study was to examine the association of IL-8 gene polymorphism with familial VUR in a cohort of 219 siblings from 109 families affected with VUR, the largest such cohort tested to date. RPS was assessed using dimercaptosuccinic acid scintigraphy. Genotyping was performed in 219 siblings with VUR (157 without RPS, 62 with RPS) and 292 controls for the position -251 of IL-8 gene by polymerase chain reaction with tetra primers and gel analysis. Genotype was compared using the chi square test. Statistical significance was taken as a value of P < 0.05. There were no significant differences in IL-8 -251 genotype frequency between VUR patients and controls. Similarly, gender, severity of VUR and renal parenchymal scarring had no effect on IL-8 -251 genotype frequency. Although IL-8 urinary levels have been reported to be elevated in VUR, our data indicate that IL-8 gene is not involved in the pathogenesis of familial VUR or reflux nephropathy.

Topics: Chelating Agents; Cohort Studies; Female; Genetic Predisposition to Disease; Humans; Interleukin-8; Kidney; Kidney Diseases; Male; Polymerase Chain Reaction; Polymorphism, Genetic; Radionuclide Imaging; Sex Distribution; Siblings; Succimer; Vesico-Ureteral Reflux

Statins reduce lipid levels, inflammation and cardiovascular events in patients with coronary artery disease; CKD patients show increased risk of cardiovascular and increased plasma levels of IL-6 and IL-8.. To evaluate the in vitro effect of simvastatin (S) or fluvastatin (F) on the lipopolysaccharide (LPS) stimulated secretion of IL-6 and IL-8 from monocytes of chronic kidney disease patients (CKD) in K-DOQI stages 3-5.. Monocytes enriched peripheral blood (PBMC) from 28 CKD (15 in K-DOQI stages 3-4, Group I, and 13 in K-DOQI stage 5 on hemodialysis, Group II) and 10 healthy subjects (HS), were isolated by Ficoll-gradient centrifugation. Cells were incubated with LPS 100 ng/ml or with LPS plus increasing doses of statins (from 10(-6) to 10(-8) M ) for 24 h. Surnatant IL-6 and IL-8 concentrations were determined by EIA.. Basally the mean concentration of IL-6 and IL-8 was higher in patients than in HS and in Group II than in Group I (IL6: HS 285 +/- 77 pg/ml, Group I 365 +/- 178 pg/ml, Group II 520 +/- 139 pg/ml- IL8 HS 180 +/- 75 pg/ml, Group I 1722 +/- 582 pg/ml, Group II 4400 +/- 1935 pg/ml). After addition of LPS the mean concentration of IL-6 and IL-8 increased in all groups (IL6: HS 1740 +/- 178 pg/ml, Group I 3754 +/- 672 pg/ml, Group II 4800 +/- 967 pg/ml; IL8: HS 450+/-132 pg/ml, Group I 9700+/-2837 pg/ml, Group II 11608 +/- 2316 pg/ml). After the addition of LPS plus increasing doses of S or F from 10(-10) to 10(-6) M, a significantly lower cytokine concentration compared to the data after LPS alone was observed (IL6: HS 45%, Group I 75%, Group II 50%; IL8: HS 100%, Group I 65%, Group II 35%).. These data confirm that cytokine release is increased in CKD patients and that is highest in the most severe patients. Furthermore they suggest that fluvastatin or simvastatin can be used in order to reduce the high cardiovascular risk.

Topics: Cardiovascular Diseases; Cells, Cultured; Chronic Disease; Cytokines; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Indoles; Interleukin-6; Interleukin-8; Kidney Diseases; Lipopolysaccharides; Monocytes; Simvastatin

Mast cells are growth factor-rich, bone marrow-derived cells that infiltrate injured tissue where they have been implicated in the pathogenesis of progressive fibrosis.. Mast cell infiltration and the expression of related chemoattractants was examined following 5/6 nephrectomy, a model of progressive, nonimmune-mediated renal injury. In addition, expression of the profibrotic cytokine, transforming growth factor-beta (TGF-beta) within mast cells and the effects of renoprotective therapy with angiotensin-converting enzyme (ACE) inhibition were also determined.. Renal injury was accompanied by mast cell infiltration, in close proximity to areas of tubulointerstitial fibrosis. Mast cells displayed toluidine blue metachromasia and were immunopositive for TGF-beta1 as well as chymase and tryptase. The expression of several mast cell chemokines, including stem cell factor, interleukin-8 (IL-8), and also TGF-beta1, were increased in 5/6 nephrectomized kidneys. ACE inhibition with ramipril led to a reduction in renal injury in association with attenuation of mast cell infiltration and chemokine expression.. Mast cell infiltration and related chemokine expression are prominent and early features following renal mass reduction and may contribute pathogenetically to progressive renal injury.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Chemokines; Disease Progression; Interleukin-8; Kidney Diseases; Macrophages; Male; Mast Cells; Nephrectomy; Ramipril; Rats; Rats, Sprague-Dawley; Stem Cell Factor; Transforming Growth Factor beta; Transforming Growth Factor beta1

Cytokines are small regulatory peptides with diverse functions. They regulate the immune system and modulate the inflammatory response, both of which are implicated in vesico-ureteric reflux (VUR) and associated reflux nephropathy (RN). The cytokine profile in VUR and RN has yet to be fully investigated. Blood was obtained from three subject groups immediately after induction of anaesthesia: group A [subjects with VUR and established RN, (N=9)]; group B [VUR alone but no associated RN, (N=6)]; and group C [age- and sex-matched controls with no history of urinary sepsis, (N=14)]. Serum cytokine levels of tumour-necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), soluble TNF receptor-1 (sTNF-R1), and interleukin-8 (IL-8) were measured using standard ELISA technique. Serum levels of IL-6 were higher in group A subjects (1.798-4.638 pg/ml, median 3.253 pg/ml) than controls (1.531-2.078 pg/ml, median 1.798 pg/ml). There was no significant difference in levels in group B subjects (1.498-3. 048 pg/ml, median 1.948 pg/ml) and controls. These same relationships were observed for levels of TNF-alpha (group A: 8. 501-14.471 pg/ml, median 13.483 pg/ml; group B: 7.088-10.650 pg/ml, median 8.886 pg/ml; group C: 6.746-13.344 pg/ml, median 7.671 pg/ml) and sTNF-R1 (group A: 690.34-5780.74 pg/ml, median 1197.38 pg/ml; group B: 366.65-1401.62 pg/ml, median 592.82 pg/ml; C: 313.49-636.33 pg/ml, median 504.17 pg/ml). IL-8 was not significantly elevated in any of the study groups (A or B) compared with control group C (group A: 27.08-56.38 pg/ml, median 31.35 pg/ml; group B: 29.90-35. 87 pg/ml, median 31.35 pg/ml; group C: 25.05-30.22 pg/ml, median 29. 90 pg/ml). These results suggest there may be an immunological basis to RN.

Topics: Adolescent; Antigens, CD; Child; Child, Preschool; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant; Interleukin-6; Interleukin-8; Kidney Diseases; Male; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Tumor Necrosis Factor-alpha; Vesico-Ureteral Reflux

Previously it has been demonstrated that human proximal tubular epithelial cells (PTEC) are able to produce chemokines (such as IL-8 and MCP-1) and complement components (such as C2, C3, C4 and factor H), and that production of these proteins is regulated by pro-inflammatory cytokines such as interleukin-1 alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). Since TGF-beta is also expressed in the renal interstitium during inflammation, we investigated the effect of TGF-beta on the production of chemokines and complement components by PTEC in culture. Transforming growth factor-beta 1 up-regulated IL-8 production by an average of 4.17 +/- 1.0 fold. macrophage chemoattractant phagocyte (MCP-1) production, on the other hand, was down-regulated by TGF-beta 1 by an average of 2.2 +/- 0.7 fold. The production of C3 and C4 was also down-regulated after incubation with TGF-beta 1 (1.9 +/- 0.3- and 3.0 +/- 1.2-fold, respectively). All effects were dose- and time-dependent and were found to be specific for TGF-beta 1, as assessed by inhibition of the effect with a neutralizing antibody against TGF-beta 1. These data, together with the knowledge that TGF-beta, chemokines and complement components play a role in several types of renal disease, suggest that TGF-beta is involved in the regulation of local expression of chemokines and complement components by tubular cells.

Topics: Antibodies, Monoclonal; Cell Line; Chemokine CCL2; Chemokines; Complement C3; Complement C4; Complement System Proteins; Dose-Response Relationship, Drug; Humans; Interleukin-8; Kidney Diseases; Kidney Tubules, Proximal; Kinetics; Transforming Growth Factor beta

Plasma levels of some pro-inflammatory cytokines and soluble adhesion molecules have been suggested to be useful parameters to assess the activity of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis and lupus nephritis. We hypothesized that the renal activity of these diseases is better reflected by the urinary excretion and fractional excretion of these molecules.. Plasma levels and urinary excretion of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8, and the soluble cell adhesion molecules sICAM-1 and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 14 patients with ANCA-positive renal vasculitis (eight active, ANCA-A; six in remission, ANCA-R), six patients with active lupus nephritis (LN), 15 patients with IgA nephropathy (IgAN) and nine healthy subjects. Fractional excretion of selected cytokines and adhesion molecules was also calculated.. Patients with ANCA-A had increased urinary excretion and fractional excretion of TNF-alpha (9.27 +/- 3.19% vs 0.58 +/- 0.02%, P < 0.01), IL-6 (120.79 +/- 65.83% vs 1.89 +/- 0.34%, P < 0.01) and increased fractional excretion of IL-8 (23.34 +/- 6.38% vs 2.56 +/- 1.07%, P < 0.01) and sVCAM-1 (0.81 +/- 0.33% vs 0.03 +/- 0.02%, P < 0.01) compared with controls. Urinary excretion of TNF-alpha and IL-6 and fractional excretion of TNFalpha, IL-6 and IL-8 were higher in ANCA-A than in ANCA-R. Patients with LN had increased plasma TNF-alpha (20.52 +/- 2.01 pg/ml vs 12.33 +/- 0.23 pg/ml, P < 0.05) and sVCAM-1 (1537.88 +/- 276.36 ng/ml vs 692.26 +/- 44.42 ng/ml, P < 0.05) and increased urinary excretion of TNF-alpha (2.81 +/- 0.51 microg/mol creat vs 0.98 +/- 0.05 microg/mol creat, P < 0.01), IL-8 (35.78 +/- 14.03 microg/mol creat vs 12.46 +/- 5.19 microg/mol creat, P < 0.05) and sVCAM-1 (48.98 +/- 20.20 microg/mol creat vs 2.92 +/- 1.35 microg/mol creat, P < 0.01) compared with controls. Patients with IgAN had, in comparison with controls only increased plasma TNF-alpha (18.10 +/- 0.57 pg/ml vs 12.33 +/- 0.23 pg/ml, P < 0.05).. Urinary excretion and fractional excretion, but not plasma levels, of selected pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-8) were increased in patients with active ANCA-positive renal vasculitis, but not in ANCA positive vasculitis in remission. These parameters may be useful to monitor the activity of this disease.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Case-Control Studies; Cell Adhesion Molecules; Cytokines; Female; Glomerulonephritis, IGA; Humans; Immunosuppressive Agents; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Kidney Diseases; Lupus Nephritis; Male; Middle Aged; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1; Vasculitis

Chemokines are important mediators of leucocyte chemoattraction to inflammatory sites. Previous work has shown that the expression of some chemokines is upregulated during renal transplant rejection. The objectives of the present study were to determine whether chemokine expression is increased during renal transplant rejection. Immunohistochemistry was used to localize the C-X-C (alpha) chemokine interleukin-8 (IL-8) and the C-C (beta) chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1beta (MIP-1beta) in 30 needle biopsies of human kidney transplants taken for diagnosis of renal dysfunction. Urine samples from transplant patients taken immediately prior to biopsy were assayed for chemokine content using enzyme-linked immunosorbent assays (ELISAs). Results from groups of patients having different clinicopathological diagnoses were then compared. All three chemokines were detected in most renal transplant biopsies showing acute cellular rejection but, although infiltrating leucocytes were often positive, staining was predominantly localized to renal tubular epithelium. Staining for MCP-1 was generally weaker than for the other chemokines, and collecting tubules were usually stained more strongly than proximal convoluted tubules. Tubular epithelial staining was also found in biopsies from patients without signs of acute cellular rejection. There were significantly higher amounts of IL-8 in the urine of patients with acute cellular rejection, even when patients with urinary tract infections were excluded, but mean titres of urinary MIP-1beta did not differ between patient groups. This was also found when titres were normalized for urine volume and creatinine levels. Production of IL-8, MCP-1 and MIP-1beta is not confined to kidney transplants showing acute cellular rejection, and may be a relatively nonspecific response of tubular epithelial cells to renal damage.

Topics: Acute Disease; Adult; Chemokine CCL2; Chemokine CCL4; Chemokines, CC; Chemokines, CXC; Epithelial Cells; Female; Graft Rejection; Humans; Interleukin-8; Kidney Diseases; Kidney Transplantation; Kidney Tubules; Macrophage Inflammatory Proteins; Male; Middle Aged; Staining and Labeling

Elevation of urinary levels of interleukin-6 and 8 has been observed in patients with acute urinary tract infections. However, to our knowledge there have been no studies concerning the secretion of interleukin-6 and 8 into the urine after acute inflammation has resolved and renal scarring has occurred. On the other hand, it is well known that cytokines are variously related to glomerular diseases and, thus, it is possible that the progression of reflux nephropathy depends on interleukin-6 or 8. Therefore, we assessed urinary levels of interleukin-6 and 8 in children with vesicoureteral reflux and/or renal scarring.. We evaluated interleukin-6 and interleukin-8 levels in the urine of 32 children without a urinary tract infection who presented or were admitted to our hospital because of vesicoureteral reflux between April and December 1994. Interleukin-6 and 8 were determined using a commercially available human enzyme-linked immunosorbent assay kit and the 2-step sandwich method.. Urinary interleukin-6 levels were below the lower detection limit (less than 10 pg./ml.) in all samples. There were statistically significant differences between urinary interleukin-8 levels in children with and without renal scarring (p = 0.001), and with and without vesicoureteral reflux (p = 0.0246).. Urinary interleukin-8 is an effective marker for renal scarring and vesicoureteral reflux.

Topics: Adolescent; Child; Child, Preschool; Cicatrix; Female; Humans; Interleukin-6; Interleukin-8; Kidney Diseases; Male; Vesico-Ureteral Reflux

Topics: Aged; Female; Humans; Interleukin-8; Kidney Diseases; Polyarteritis Nodosa

IL-8 is a chemotactic cytokine with proinflammatory and growth-promoting activities. The release of IL-8 was measured in supernatants of cultured peripheral blood monocytes (PBM) that were obtained from patients with glomerulonephritis (GN) and healthy controls. Spontaneous and lipopolysaccharide (LPS)-induced IL-8 release was significantly higher in PBM isolated from patients with IgA nephropathy (IgAN) and membranous nephropathy (MN) compared with normal controls. These results raise the question of whether IL-8 contributes to the ongoing pathogenesis of GN. We cannot relate IL-8 release to clinical and laboratory parameters in IgAN and MN patients. Thus, disease progression in vivo may not be accompanied by increased or sustained IL-8 release.

Topics: Adolescent; Adult; Aged; Female; Glomerulonephritis; Humans; Interleukin-8; Kidney Diseases; Lipopolysaccharides; Male; Middle Aged; Monocytes; Prospective Studies

CAPD-related peritonitis was used as an in-vivo model to study Il-8 during peritoneal inflammation. Eleven episodes were studied in nine patients, who were followed on 8 consecutive days from the start of peritonitis and once after recovery (control). Il-8 was measured in dialysate (night dwells) and serum. The Il-8 time course was compared to Il-6 and TNF alpha. In addition, an in-vivo relationship between dialysate Il-8 and intraperitoneal accumulation of neutrophils was studied. A highly increased peritoneal appearance rate of Il-8 was found in the acute phase that decreased to control values during recovery. A remarkable parallelism was observed for dialysate Il-8 and Il-6 with respect to the time course and the peritoneal appearance rate. In contrast, the appearance rate of TNF alpha was much less and had a different time course. In three of four cases where the dialysate Il-8 peak occurred on day 2, the dialysate Il-6 peak still coincided with Il-8, in contrast to TNF alpha (always day 1). Dialysate Il-8 generally exceeded serum concentrations during the entire follow-up, indicating intraperitoneal Il-8 synthesis. A positive correlation was present between the dialysate Il-8 peak and the maximal number of neutrophils in dialysate. This relationship was absent for Il-6 and TNF alpha. In five of six episodes where neutrophils were quantified on both day 1 and 2, the Il-8 peak occurred simultaneously with the neutrophil peak. These findings suggest that Il-8 is involved in the recruitment of neutrophils towards the dialysate during peritonitis.

Topics: Acute Disease; Adult; Aged; Ascitic Fluid; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Kidney Diseases; Leukocytes; Male; Middle Aged; Models, Biological; Neutrophils; Peritoneal Cavity; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Time Factors; Tumor Necrosis Factor-alpha

Growing evidence suggests that cytokine expression is influenced by locally produced mediators, thus modifying the pluripotential effects of cytokines toward a tissue-specific inflammatory reaction. The granulocyte inhibitory protein (GIP), a 23-kDa protein found to be significantly overexpressed in patients with chronic renal failure, increases autocrine transcription and expression of interleukin (IL) 6 and IL-8 in human mesangial cells. Moreover, GIP alone induced the transcription of c-jun mRNA; however, in combination with IL-6, it stimulated de novo synthesis of DNA and the transcription of both c-jun and c-fos genes. The data suggest that the overall effect of GIP results in the modulation of the glomerular response to injury and contributes to the progression of glomerulosclerosis.

Topics: Cells, Cultured; Cytokines; Gastric Inhibitory Polypeptide; Gene Expression; Humans; In Vitro Techniques; Interleukin-6; Interleukin-8; Kidney Diseases; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; RNA, Messenger; Transcription, Genetic