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Objectives: To analyze factors during early stage of urinary tract infection (UTI) that are associated with development of chronic UTI., Methods: Mice were inoculated with Uropathogenic Escherichia coli (UPEC) 2 times 24 hours apart. At 1, 3, 7, 10, 14, 21 and 28 days post infection (dpi), urine bacterial loads and voiding behavior (voiding spot assay, VSA) were measured. At 1 and 28 dpi, 32 urine inflammatory cytokines/chemokines were measured using enzyme-linked immunosorbent assay (ELISA). Bladder and kidney cytokines/chemokines were measured on 28 dpi. Mice that had no more than 1 episode of urine bacterial load < 10 4 colony forming unit/ml during the entire 4 weeks were defined as susceptible to chronic UTI, otherwise, mice were considered resistant., Results: At 28 dpi, 64.3% mice developed chronic UTI (susceptible group) and 35.7% mice did not (resistant group). Factors at 1 dpi that were predictive of chronic UTI included increased urine IL-2 (OR 11.9, 95%CI 1.1-130.8, P = .043) and increased urine IL-10 (OR 14.0, 95%CI 1.0-201.2, P = .052). At 28 dpi, there were several significant differences between the susceptible vs resistant groups including urine/tissue bacterial loads and certain urine/tissue cytokines/chemokines., Conclusions: Higher urine IL-2 and IL-10 at 1 dpi predicted chronic UTI infection in this model. There have been recent publications associating both of these cytokines to UTI susceptibility. Further explorations into IL-2 and IL-10 mediated pathways could shed light on the biology of recurrent and chronic UTI which are difficult to treat., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: To identify predictors of perioperative complications in children with obstructive uropathy., Materials and Methods: A total of 178 patients with obstructive uropathy were divided into 3 groups. In Group 1 there were 108 children with hydronephrosis, while Group 2 included 47 children with ureterohydronephrosis and Group 3 consisted of 23 children with bladder outlet obstruction according to the results of clinical, laboratory, microbiological, X-ray and pathologic study. The evaluation of the urine level of pro- (IL-8) and anti-inflammatory (IL-10) cytokines was performed at two timepoints, prior to treatment (1 point) and on the 3-5th day after the surgery (2 point) using "Vector - Best" (Russia, Novosibirsk) (IL-8), "Bender Medsystems" (Austria) (IL-10) on the enzyme immunoassay analyzer Stat Fax 2010 (USA)., Results: The active phase of chronic pyelonephritis was shown in Groups 1, 2 and 3 in 38%, 36% and 100% of cases, respectively. Microbiological examination of urine allowed to identify a causative agent in 85% and 89% of biopsy specimens from the ureteropelvic and ureterovesical junction, respectively. In all groups, Escherichia coli was a main pathogen (40%). In 25% of patients of Groups 1 and 2, isolated pathogens in biopsy specimen and urine were different. According to the evaluation of cytokines in the urine, during the active phase of chronic pyelonephritis there was an increase in the level of IL8 (p<0.0001) at points 1 and 2 in all patients. In the latent phase of inflammation, there was an increase in the concentration of IL-8 (p<0.04) and IL-10 (p<0.002) at point 2 in Groups 1 and 2. Using the ratio of IL-8 and IL-10, an index of inflammation activity (IIA) was suggested, whose values were increased in all Groups at point 1 and 2. Based on the regression analysis of the changes in IIA level, a model for predicting perioperative complications and an algorithm for personalized patient management were developed., Conclusion: Cytokines are indicators of latent inflammation in children with OU and may be predictors of perioperative complications.

Background: This study investigated the association between urinary levels of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) with estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (uACR), and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in patients with type 2 diabetes (T2D)., Methods: Urinary concentrations of IL-6, IL-10, TNF-α, ACR, and NGAL were measured in 121 patients with T2D., Results: Urinary IL-6 and TNF-α increased 45.5% and 49.4% in the highest uACR quartile compared to lowest quartile. Urinary IL-10 levels decreased 40.9% in the highest uACR quartile compared to the lowest quartile. Urinary IL-6 and TNF-α were 75.3% and 81.6%, higher in the highest uNGAL quartile compared to the lowest quartile. Urinary IL-10 concentration was 69.8% lower in patients from the highest uNGAL quartile compared to lowest quartile., Conclusions: Urinary IL-6, IL-10, and TNF-α were associated with indicators of glomerular and tubular injuries in patients with T2D.

Background: The aim of this study was to investigate the expression of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) in expressed prostatic secretions (EPSs) of patients with chronic prostatitis (CP) and the expression of prostatic exosomal protein (PSEP) in urine, and to evaluate its correlation with the condition., Methods: Urine samples from 310 patients with CP (101 National Institutes of Health [NIH] II, 112 NIH IIIa, and 97 NIH IIIb, classified according to the US National Institutes of Health) and 110 control group subjects were collected. The samples were tested for PSEP by enzyme-linked immunosorbent assay (ELISA). At the same time, EPSs in 60 patients from 310 patients with CP and 20 control group subjects were collected. The levels of IL-10 and TNF-α in the collected samples that EPS were determined by double antibody sandwich ELISA. SPSS 23.0 statistical software was used for statistical analysis of the measured data., Results: The level of PSEP in patients with CP was significantly higher than that in the control group (P < .001). The levels of TNF-α and IL-10 in the EPS of patients with NIH II and NIH IIIa CP were higher than those of the patients with NIH IIIb and the control group (P < .001). There was a positive correlation between PSEP and IL-10 and TNF-α, while TNF-α and IL-10 were also positively correlated., Conclusion: PSEP, TNF-α, and IL-10 may serve as a basis for the classification diagnosis of CP. Their combination can provide more accurate diagnostic information for clinical CP typing.

We evaluated the heat shock system 70 (HSP70) in patients with chronic glomerulonephritis (CGN). Seventy-six patients with CGN patients were included in our study. Ten patients with mild proteinuria (median 0.48 [0.16-0.78] g/24 h) and ten healthy subjects served as positive and negative controls, respectively. Urinary levels of HSP70, interleukin-10, and serum levels of anti-HSP70 were measured by ELISA. The immunohistochemical peroxidase method was used to study the expression of HSP70 and Foxp3+ in kidney biopsies. Treg FoxP3+ cells in the interstitium were determined morphometrically. Median urinary HSP70 levels in patients with nephrotic syndrome (NS) [6.57 (4.49-8.33) pg/mg] and subnephrotic range proteinuria [5.7 (4.12-6.9) pg/mg] were higher (p < 0.05) than in positive [3.7 (2.5-4.82) pg/mg] and negative [3.78 (2.89-4.84) pg/mg] controls. HSP70 expression index in tubular cells positively correlated with urinary HSP70 (Rs = 0.948, р < 0.05) and proteinuria (Rs = 0.362, p < 0.05). The number of Treg Foxp3+ cells in the kidney interstitium and interleukin-10 excretion were lower in patients with NS. Anti-HSP70 antibody serum levels in patients with NS [21.1 (17.47-29.72) pg/ml] and subnephrotic range proteinuria [24.9 (18.86-30.92) pg/ml] were significantly higher than in positive [17.8 (12.95-23.03) pg/ml] and negative [18.9 (13.5-23.9) pg/ml] controls. In patients with CGN, increasing proteinuria was associated with higher HSP70 renal tissue and urinary levels. However, activation of HSP70 in patients with nephrotic syndrome did not lead to an increase in tissue levels of Treg Foxp3+ cells or to the release of IL-10.

Background: Predictive factors for the rate of decline in kidney allograft function beyond the first post-transplant year have not been thoroughly studied. We aimed to determine whether a single measurement of serum and urinary interleukin 2, interleukin 8 and interleukin 10 at 1-15 years after kidney transplantation could predict a decline in estimated glomerular filtration rate (eGFR) over a 2-year period., Results: Greater serum concentrations of interleukin 8 and interleukin 10 in 30 recipients of kidney allograft at enrollment were associated with lower eGFR after 1 year (beta = - 0.616, p = 0.002 and beta = - 0.393, p = 0.035, respectively), whereas serum concentrations of interleukin 8 also demonstrated significant association with eGFR after 2 years of follow-up (beta = - 0.594, p = 0.003). Higher urinary interleukin 2 concentrations were associated with lower eGFR at baseline (rho = - 0.368, p = 0.049) and after the first (beta = - 0.481, p = 0.008) and the second year (beta = - 0.502, p = 0.006) of follow-up. Higher urinary interleukin 2 concentrations predicted certain decline in eGFR of ≥ 25% from baseline after 1 year of follow-up in logistic regression: odds ratio = 2.94, confidence interval 1.06-8.18, p = 0.038. When combined with time after transplantation, urinary interleukin 2 demonstrated good accuracy in predicting rapid decline in eGFR by > -5 mL/min/1.73 m 2 /year (area under the receiver-operator characteristic curve: 0.855, confidence interval 0.687-1.000, and p = 0.008)., Conclusions: Our findings suggest that urinary interleukin 2 in the late period after kidney transplantation has promise in identifying patients who are at risk for progressive loss of graft function in a short-time perspective and need closer monitoring.

Objective  To investigate the level of anxiety and its relationship with interleukin (IL)-10 (anti inflammatory cytokine that modulates mood swings) in a group of female soccer players. Methods  Fifty-two eumenorrheic soccer players were evaluated (age 19.8 ± 4.7 years). The presence of premenstrual syndrome (PMS) and phases of the menstrual cycle were determined by a daily symptom report (DSR) kept for 3 consecutive months. The concentration of cytokine IL-10 was determined from urine samples collected at four moments: at the follicular and luteal phases of the menstrual cycle, and before (pre) and after (post) the simulated game, and it was quantified by flow cytometry (Luminex xMAP - EMD Millipore, Billerica, MA, USA). The level of anxiety was determined through the BAI anxiety questionnaire answered by all athletes at the same time of the urine collection. The Student t -test, analysis of variance (ANOVA) and Pearson correlation with significance level at 5% were used for data analysis. Results  We showed that the prevalence of PMS among female soccer players is similar to that reported in the literature. In addition, we showed that the group with PMS has a higher level of anxiety compared with group without PMS ( p  = 0.002). Interleukin-10 analysis in players without PMS revealed that there was a significant decrease in the level of this cytokine before the game during the luteal phase when compared with the follicular phase ( p  < 0.05). The correlation analysis between IL-10 and anxiety showed a negative correlation post-game in the luteal phase in the group without PMS ( p  = 0.02; r = -0.50) and a positive correlation post-game in the luteal phase in PMS group ( p  = 0.04; r = 0.36). Conclusion  Our results suggest that IL-10 may contribute to reduce anxiety in the group without PMS. This could be attributed to the fact that no IL-10 variation was observed in the group with PMS, which presented higher anxiety symptoms when compared with the group without PMS., Competing Interests: Conflict of Interests: Study developed at Escola Paulista de Medicina – Universidade Federal de São Paulo – UNIFESP – São Paulo, SP, Brazil. Authors declare no conflict of interest., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Objectives: In patients undergoing cardiac surgery, both extracorporeal circulation (ECC) and intraoperative mesenterial hypoperfusion may account for increased cytokine levels and lead to postoperative gastrointestinal (GI) symptoms., Methods: We investigated levels of the intestinal damage markers intestinal fatty acid binding protein (I-FABP in plasma [n = 72] and urine [n = 37]), citrulline (in plasma [n = 35]), and claudin-3 (in urine [n = 37]) in patients undergoing aortic or mitral valve surgery with or without coronary artery bypass grafting. Furthermore, the relationship between these markers and the surgery-induced cytokine response was explored by measuring serial plasma levels of tumor necrosis factor-α, interleukin (IL)-6, IL-8, and IL-10 (n = 35). Finally, the relationship between markers of intestinal damage and GI-symptoms (abdominal pain, ileus, vomiting, diarrhea, time to first defecation) was assessed., Results: Plasma and urinary I-FABP levels, and urinary claudin-3 levels peaked at the end of surgery, while citrulline levels were not influenced by surgery. ECC duration correlated with plasma I-FABP levels (r = 0.31, P = 0.007). Plasma levels of all measured cytokines increased during surgery, with peak levels observed either at the end of surgery or on the first postoperative day. While ECC duration correlated with IL-6 and IL-8 release (r = 0.43, P = 0.01 and r = 0.36, P = 0.04 respectively), there was no direct relationship between I-FABP and claudin-3 levels and cytokine concentrations. No patients developed significant GI or non-GI complications, and I-FABP and claudin-3 release appeared not to be related to postoperative GI symptoms, although the incidence of these symptoms may have limited a reliable assessment., Conclusions: Longer duration of ECC is associated with a more pronounced release of intestinal injury markers and inflammatory cytokines, but intestinal injury markers are not directly related to the observed increase in cytokine levels or GI-symptoms. These findings indicate that ECC duration contributes to the cytokine response observed in cardiac surgery patients and that intestinal injury itself is not a causative factor for this response.

The aim of the present study was to investigate the association between the presence of albuminuria and cytokines profile with biomarkers of endothelial damage and oxidative stress in patients with type 1 diabetes mellitus (DM1). The sample was composed by 35 healthy individuals, 63 DM1 patients with normoalbuminuria (<30 mg of albumin/g of creatinine) and 62 DM1 patients with micro- and macroalbuminuria (≥30 mg of albumin/g of creatinine). Plasma and urinary cytokines (TNF-α, IL-6 and IL-10) and thrombomodulin levels were determined by ELISA. Oxidative status was evaluated using the TBARS and MTT assays. Diabetic patients were characterized by elevated levels of urinary cytokines TNF-α, IL-6 and IL-10. Those with macroalbuminuria presented significantly higher TNF-α and IL-10 urinary levels when compared to other groups. Urinary and plasmatic levels of TNF-α were positively correlated with plasma levels of cystatin C, creatinine, urea and albuminuria, while they were negatively correlated with estimated glomerular filtration rate. Urinary IL-10 levels proved positive correlation with fasting glucose, HbA1c, thrombomodulin and TBARS, while IL-6 plasma levels were positively correlated with HbA1c and albuminuria. Only urinary TNF-α levels were associated with the presence and severity of macroalbuminuria, after logistic regression analysis. This finding suggests that measurement of urinary TNF-α level may be helpful to evaluate progression to nephropathy in DM1 patients.

Introduction: A lot of evidence has demonstrated the importance of different cytokines in acute renal rejection. Previous studies have examined the presence or absence of interleukin (IL)-10 in related immunopathologic rejection grafts as well as other interleukins. Studies in human transplantation show elevated levels of IL-10 and gamma interferon (INF-γ) in inflammation and rejection., Objective: The objective of this study was to demonstrate the lack of association of elevated urinary levels of IL-10 and IFN in the presence of active inflammation., Methods: An observational, descriptive, cross-sectional study conducted in transplant recipients at 12 months of follow-up after renal transplantation. In those who were held biopsy after renal transplantation at one year follow-up, or allograft dysfunction, we also measured IL-10 and INF-γ in the urine. The following were considered as variables: age, body mass index (BMI), gender, transplant type, creatinine, chronic kidney disease epidemiology collaboration equation, (CKD-EPI), modification of diet in renal disease study equation (MDRD), Banff classification, and levels of IL-10 and INF-γ. Statistical analysis was performed calculating a sample size of 25 patients, with an alpha bias of 0.05%, yielding measures of central tendency and determining no association between levels of IL-10 and INF-γ with the presence of rejection using SPSS 21.0 program., Results: A total of 50 patients, 34 (68%) males, 16 (32%) females, with an average 31.7 ± 9.9 years, weight of 64.91 ± 13.84 kg, size 1.60 ± 0.10 m and 24.97 ± 4.07 BMI were included,39 (78%) living donor and 11 (22%) cadaveric. Twenty-six (52%) showed inflammation in the biopsy and 24 (48%) showed none. Mean creatinine was 1.81 ± 1.5, and the estimated glomerular filtration rate (eGFR) was 55.27 ± 22.46, 65.76 ± 26.7. (MDRD and CKD-EPI, respectively). No statistical difference was found in the levels of IL-10 and IFN-γ using analysis of variance. (ANOVA; P = .467 and P = .063, respectively) Based on Banff, the inflammation on biopsy score was 2.78 ± 2.84. There was statistical significance (P < .05) with respect to the Cr and eGFR by different equations. There were no significant interactions between cytokine levels and more than 1 factor. (as indicated by P < .2)., Discussion and Conclusions: No significant differences were observed in the level of interleukins in patients with and without inflammation, denoting an adequate immunosuppression in most of these patients. Determination of inflammatory cytokines in urine could be used as a determinant of a good immunosuppression status, rather than as an early marker of rejection., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Glomerulonephritides (GNs) represent common causes of chronic kidney disease associated with a wide spectrum of clinical and histological features. Various factors that activate the inflammatory cascade are involved in the development of kidney injury. The aim of this study was to estimate the urinary excretion of pro-inflammatory (IL-2, INF-γ, TNF-α, IL-6, IL-17) and anti-inflammatory (IL-4, IL-10, TGF-β1) cytokines, as well as the chemokine MCP-1 in patients with various types of GN treated by immunosuppressive drugs and to identify any prognostic value of excreted cytokines for future renal function., Patients and Methods: Ninety-seven patients (62 M/35 F, age 53.1 ± 15.6 years) with primary glomerulonephritis and 32 healthy controls were studied. The original diagnoses were membranous nephropathy (MN, n=36), IgA nephropathy (IgAN, n=31) and minimal changes disease or focal segmental glomerulosclerosis (MCD/FSGS, n=30). All patients had been treated with immunosuppressive drugs and, at the time of measurement of urinary cytokine excretion, were either in clinical remission or still had active disease with persistent proteinuria., Results: GN patients had significantly higher levels of all cytokines and MCP-1 compared to healthy controls. A strong positive correlation between TGF-β1 and MCP-1 concentrations was observed in all GN patients. Increased urinary excretion of all tested cytokines apart from TNF-α and TGF-β1 was observed even in patients with clinical remission. The main difference between patients with proteinuria and those in clinical remission was the level of MCP-1 urinary excretion. The urinary excretion of MCP-1 and TGF-β1 was significantly higher in patients with MN who showed deterioration of renal function over a follow-up period of five years., Conclusions: Increased levels of cytokines are observed in the urine of patients with different types of glomerulonephritis, even after the achievement of clinical remission with the administration of immunosuppressive drugs. Urinary excretion of MCP-1 and TGF-β1 indicates the ongoing inflammatory and fibrotic processes in the kidney and is probably related to unfavourable outcomes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The study was organized to provide additional characteristic of chronic dysfunction of renal allo-transplant using such biomarkers of serum and urine as enzymes (alanine aminotransferase), aspartate aminotransferase, gamma- glutamiltransferase, alkaline phosphatase, N-acetyl-β-D-glucosaminidase, interleukins (IL-2, IL-8, IL-10), beta-2- microglobulin. The chronic dysfunction of renal allo-transplant is characterized by increasing of concentration of IL-10 and beta-2-microglobulin in serum and increasing of concentration of beta-2-microglobulin, IL-2, IL-8 in urine and increasing of activity of N-acetyl-β-D-glucosaminidase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamiltransferase as compared with patients with satisfactory function of renal allo-transplant. The multivariant logistic regression analysis established that only activity of N-acetyl-β-D-glucosaminidase in urine was reliably independently related to chronic dysfunction of renal allo-transplant. It is assumed that increasing of concentration of beta-2-microglobulin in serum testifies glomerular dysfunction and in urine--tubular dysfunction of renal allo-transplant. The enzymeuria indicates continuing damage of epithelium of proximal tubules of nephron. The classification of patients with satisfactory function and chronic dysfunction of renal allo-transplant established that the highest indicators of square under ROC-curves had concentration of beta-2-microglobulin in serum (0.858 ± 0.061) and urine (0.733 ± 0.079) and activity of N-acetyl-β-D-glucosaminidase in urine (0.701 ± 0.061). To specify diagnosis of chronic dysfunction of renal allo-transplant the most useful (ratio of likelihood of positive result 10 and 11 correspondingly) are tests of beta-2- microglobulin in serum (more than 8.55 mkg/ml) and N-acetyl-β-D-glucosaminidase/creatinine in urine (more than 34 nmol/(sl)/ mmol/l). These discoveries require further validation and confirmation by implementation of morphological analysis of bioptat of renal allo-transplant.

Objective: We studied the urinary sediment mRNA level of Th9- and Th22-related cytokines in patients with systemic lupus erythematosus (SLE)., Methods: We quantified urinary mRNA levels of interleukin (IL) 9, IL-10, IL-22, and their corresponding transcription factors in 73 patients with active lupus nephritis, 13 patients with hypertensive nephrosclerosis (HTN), and 25 healthy subjects., Results: There was no detectable IL-9 mRNA in all samples. Patients with proliferative lupus nephritis had significantly lower urinary IL-22 mRNA levels than those with nonproliferative nephritis (2.2 ± 5.4 vs 8.6 ± 20.0 copies, p = 0.019), and urinary IL-22 mRNA level inversely correlated with the histological activity index (r = -0.427, p < 0.0001). In contrast, patients with lupus nephritis had significantly higher urinary IL-10 mRNA levels than patients with HTN (7.8 ± 18.5 vs 1.9 ± 4.0 copies, p = 0.012), and urinary IL-10 mRNA levels correlated with its intrarenal mRNA levels (r = 0.337, p = 0.004) and SLE disease activity index (r = 0.277, p = 0.018). Urinary IL-10 mRNA level was significantly lower among patients who achieved complete remission than those with partial remission or no response (4.1 ± 6.5 vs 14.1 ± 28.0 copies, p = 0.036)., Conclusion: Urinary IL-22 mRNA level is decreased in patients with SLE with proliferative nephritis, while urinary IL-10 mRNA levels correlates with its intrarenal mRNA level and disease activity. Urinary IL-10 mRNA levels may also predict treatment response. These results suggest that urinary mRNA levels of IL-10 and IL-22 might be used as biomarkers for assessing disease activity and risk stratification in lupus nephritis.

Background: Inflammation is implicated in many adverse health conditions, and recent interest has focused on the effects of chronic low-grade inflammation in generally healthy populations. Cytokines measured in plasma or serum are commonly used as biomarkers of systemic levels of inflammation. Measurement of cytokines in urine may offer a simpler and less invasive alternative, although the degree to which levels of cytokines correlate in plasma and urine among healthy individuals is unknown., Materials and Methods: We assessed the correlation of blood and urine levels of 13 cytokines, including interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p70) and IL-13, granulocyte macrophage colony-stimulating factor, interferon gamma and tumour necrosis factor alpha in 61 healthy women aged 18-30. Cytokine concentrations were considered with and without correction for creatinine., Results: Plasma and urine levels of the 13 cytokines were not significantly correlated using measured urinary cytokine concentrations and after adjustment for creatinine. Correlation coefficients for log-transformed cytokine concentrations in paired plasma and urine specimens ranged from -0.28 to 0.087., Conclusions: These results suggest that urine has limited utility as a proxy for plasma for the measurement of inflammatory factors in a healthy population with low levels of inflammation., (© 2015 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Pathological changes due to infection with Schistosoma haematobium include cytokine-mediated urinary tract inflammation. The involved cytokines may be excreted in urine and their presence in urine may therefore reflect S. haematobium-related urinary tract pathology. The present study, for the first time, reports on the relationship between selected cytokines in urine and infection with S. haematobium in children from an area highly affected by this parasite., Methods: Children aged 5-12 years from two primary schools in Tana Delta District of Kenya were examined for S. haematobium eggs using urine filtration technique, for haematuria using dipstix and for eosinophil cationic protein (ECP), IL-6, IFN- γ, TNF-α and IL-10 levels using ELISA, and for S. haematobium-related urinary tract pathology using ultrasonography. In addition, venous blood was examined for serum IL-6, IFN- γ, TNF-α and IL-10 levels using ELISA., Results: There was no significant correlation between urinary and serum levels of IL-6, IFN- γ, TNF-α or IL-10. There was no significant difference in geometric mean intensity (GMI) in any of the serum cytokines, or in urinary TNF-α or IFN-γ, between children with light and heavy S. haematobium infections. However, children with heavy S. haematobium infections had significantly higher GMI of urinary IL-6 (p < 0.001) and lower GMI of urinary IL-10 (p = 0.002) than children with light infections. There was also a significant positive correlation between urinary IL-6 and urinary ECP (p < 0.001) and a significant negative correlation between urinary IL-10 and urinary ECP (p = 0.012)., Conclusion: Urinary IL-6 was positively correlated to and IL-10 was negatively correlated to infection intensity and urinary tract inflammation in S. haematobium-infected children. Urinary IL-6 and IL-10 ELISA may be a useful non-invasive tool to complement the already available tools for studying S. haematobium-related urinary tract pathology in children.

Objective: We examined the value of inflammatory and oxidative biomarkers in predicting acute kidney injury (AKI) following orthotopic liver transplantation (OLT)., Methods: Urinary excretion of tumour necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-10 (IL-10), superoxide dismutase (SOD), malondialdehyde (MDA), 6-keto prostaglandin F1α (6-keto-PGF1α), hydrogen peroxide (H2O2), and 8-keto prostaglandin F2α (8-iso-PGF2α), serum creatinine (SCr), blood urea nitrogen (BUN), urinary N-acetyl-beta-D-glucosaminidase (NAG), β2-microglobulin (β2-MG) and γ-glutamyl-transferase (γ-GT), were measured before surgery (baseline), at 2 h after graft reperfusion and 24 h after OLT in 28 liver transplantation patients., Results: The levels of TNF-α, IL-8, IL-10, SOD, MDA, 6-keto-PGF1α, H2O2 and 8-iso-PGF2α in urine were all significantly higher in patients who had AKI than in those who did not at 2 h after graft reperfusion and 24 h after OLT (p < 0.01).

Bladder cancer (BCA) is one of the most common cancers. In 2010 in Poland, 6296 people developed bladder cancer and 3110 people died of it. Immunotherapy with BCG (Bacillus Calmette-Guérin) is by far the most effective adjuvant therapy. Noninfiltrating muscle membrane changes, that is, stages Ta, Tis and T1 qualify for BCG immunotherapy. BCG immunotherapy comprises series of bladder instillations, containing attenuated strain of Mycobacterium bovis. The effectiveness of immunotherapy in non-invasive bladder cancer is 70% 5-year survival without recurrence of the tumor. The treatment leads to a reduction of the residual tumor mass, but also to the delay and/or prevention of relapse, disease progression and ultimately death. Cytokines, as key mediators of immune response, play an important role in the pathogenesis of bladder cancer, which occurrence is stimulated by the inflammatory process. BCG immunotherapy provokes an intensive immunological response by the increase of cytokine production. Genetic variants determine inter-individual differences in the incidence of this cancer, as well as the response to the therapy. This is evidenced by the presence of differences in genetic variants of cytokines correlated with the varied risk of bladder cancer incidence. It is believed that concentrations of particular cytokines in urine after installation of BCG may indicate response to the therapy. Increased levels of Th1 cytokines - IFN-γ, IL-2 and TNF-α are correlated with longer survival time without recurrence, whereas high levels of Th2 cytokines such as IL-10, predict unsuccessful BCG therapy.

Neutrophil gelatinase-associated lipocalin (NGAL) has been demonstrated to be a novel biomarker in acute and chronic kidney disease. We hypothesized that 24-hour urinary NGAL excretion may be a predictor for renal damage in patients with systemic lupus erythematosus (SLE). Thirty-four SLE patients with renal involvement (SLE-renal group), 8 SLE patients without renal involvement (SLE-nonrenal group), 14 patients with non-SLE autoimmune diseases (disease control or DC group), and 12 healthy volunteers (normal control or NC group) were compared for 24-hour urinary excretion of NGAL and different cytokines. We found that the 24-hour urinary NGAL excretion in the SLE-renal group was higher than that in the SLE-non-renal, DC, and NC groups. However, the excretion of interleukin-10, transforming growth factor-β1, and tumor necrosis factor-α was not different between the SLE-renal and SLE-non-renal groups. Furthermore, NGAL excretion in the SLE-renal group was correlated with serum creatinine levels and creatinine clearance, but not with the SLE Disease Activity Index score. Multivariate logistic regression analysis and receiver operating characteristic curve analysis revealed that 24-hour urinary NGAL excretion is a potential biomarker for renal damage in SLE patients, with higher sensitivity and specificity than anti-dsDNA antibody titers.

In this study, we investigated in groups of female BALB/c mice injected with Crotalus durissus terrificus venom (Cdt) the renal function based on creatinine clearance, percentage of fractional excretion cytokines and histological examination of renal tissue. Cdt caused renal alterations that induced proteinuria during the initial hours post-venom and reduced creatinine clearance 15 min. up to 2 hours post-venom administration. In urine from mice injected with Cdt induced a decrease in IL-4 levels. More pronounced increments of IL-5, IL-6 and IFN-γ were observed after 15 and 30 min, respectively. The highest levels of TNF and IL-10 were observed at 1 and 4 hs, respectively. The ratios of pro- and anti-inflammatory cytokines in animals injected with Cdt, which may be manifested in the inflammatory status during the envenoming. In groups of animals treated with Cdt were observed a decreasing in creatinine clearance and its effect on glomerular filtration rate was accompanied by decreased fractional excretion of cytokines and morphologic disturbances. This loss of change selectively in envenomation could thus explain why the relatively excretion of cytokines is reduced while of total proteins increases. In conclusion the fractional excretion of cytokines is significantly reduced in mice injected with Cdt, despite proteinuria.

Background: Crucial inflammatory mediators involved in development of alloimmune response leading to AR are cytokines. Our project was aimed to investigate the relation between the urine cytokine profile and the development of acute rejection (AR) episodes in patients after kidney transplantation., Material/methods: The project included 44 patients undergoing kidney transplantation. During the six-month period following the transplantation AR was diagnosed in 11 patients. Urine samples were collected 2, 4, 14 and 30 days posttransplantation and cytometrically tested for concentrations of IL-2, IL-4, IL-5, IL-10, IFN-gamma and TNF-alpha., Results: We found the elevated posttransplant concentrations of IFN-gamma, IL-10 and TNF-alpha in the urine of patients with diagnosed AR vs. NONAR (P<.05). No significant differences in the urine concentrations of IL-2, IL-4, IL-5 between the two groups were observed (P>.05). Elevated concentrations of urine IFN-gamma and TNF-alpha in AR patients, not accompanied by higher concentrations of IL-2, may suggest an ongoing undetected nonspecific Th1 immune response, capable of amplifying the alloimmune response in the early phase postsurgery, leading to AR. Higher concentrations of IL-10 found in the urine of AR patients, in turn, can partially result from peripheral regulatory mechanisms controlling the ongoing immune reaction, and partially from activation of monocytes/macrophages., Conclusions: The results of our study suggest that higher concentrations of IFN-gamma, TNF-alpha and IL-10 in the urine of patients shortly after the kidney transplantation can be considered as risk factors increasing the probability of AR episodes.

Background: The early evolution of acute kidney injury (AKI) in humans is difficult to study noninvasively. We hypothesized that urine proteomics could provide insight into the early pathophysiology of human AKI., Study Design: A prospective nested case-control study (n = 250) compared serial urinary proteomes of 22 patients with AKI and 22 patients without AKI before, during, and after cardiopulmonary bypass surgery., Outcomes: AKI was defined as a greater than 50% increase in serum creatinine level, and non-AKI, as less than 10% increase from baseline., Measurements: Serum creatinine, urine protein-creatinine ratio, neutrophil gelatinase-associated lipocalin (NGAL), alpha1-microglobulin, interferon-inducible protein-10 (IP-10), monokine induced by interferon gamma (Mig), interferon-inducible T cell alpha chemoatractant (I-TAC), interleukin 6 (IL-6), IL-1beta, and IL-10. Urine protein profiling by means of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS)., Results: SELDI-TOF-MS showed intraoperative tubular stress in both groups on arrival to the intensive care unit, evidenced by beta2-microglobulinuria. Non-AKI proteomes returned toward baseline postoperatively. In contrast, AKI proteomes showed a second phase of tubular injury/stress with the reappearance of beta2-microglobulin and multiple unidentified peaks (3 to 5 and 6 to 8 kDa) and the appearance of established tubular injury markers: urinary protein, alpha1-microglobulin, and NGAL. Furthermore, 2 novel peaks (2.43 and 2.78 kDa) were found to be dominant in postoperative non-AKI urine samples. The 2.78-kDa protein was identified as the active 25-amino acid form of hepcidin (hepcidin-25), a key regulator of iron homeostasis. Finally, an inflammatory component of reperfusion injury was evaluated by means of enzyme-linked immunosorbent assay analysis of candidate chemokines (IP-10, I-TAC, and Mig) and cytokines (IL-6, IL-1beta, and IL-10). Of these, IP-10 was upregulated in patients with versus without AKI postoperatively., Limitations: This is an observational study. SELDI-TOF-MS is a semiquantitative technique., Conclusions: Evaluation of human AKI revealed early intraoperative tubular stress in all patients. A second phase of injury observed in patients with AKI may involve IP-10 recruitment of inflammatory cells. The enhancement of hepcidin-25 in patients without AKI may suggest a novel role for iron sequestration in modulating AKI.

Inflammatory bowel disease (IBD) is a chronic debilitating disorder that is thought to have both genetic and environmental contributors. Commensal microflora have been shown to play a key part in the disease process. Metabolomics, the study of large numbers of small molecule metabolites, has demonstrated that disease and/or changes in gut microbial composition modulate mammalian urine metabolite fingerprints. The aim of this project was to associate the development of IBD with specific changes in a mouse urinary metabolic fingerprint. Interleukin-10 (IL-10) gene-deficient mice were raised alongside age-matched 129/SvEv controls in conventional housing. Urine samples (22 h) were collected at ages 4, 6, 8, 12, 16, and 20 weeks. Metabolite concentrations were derived from analysis of nuclear magnetic resonance spectra, and both multivariate and two-way analysis of variance (ANOVA) statistical techniques were applied to the resulting data. Principal component analysis and partial least-squares-discriminant analysis of urine derived from the control and IL-10 gene-deficient mice revealed that while both groups initially had similar metabolic profiles, they diverged substantially with the onset of IBD as assessed through external phenotypic changes. Several metabolites, including trimethylamine (TMA) and fucose, changed dramatically in the IL-10 gene-deficient mice following 8 weeks of age, concomitant with the known timeline for development of severe histological injury. This study illustrates that metabolomics is effective at distinguishing IBD using urinary metabolite profiles.

Purpose: Several potential markers have been investigated to improve the noninvasive diagnosis of recurrent superficial bladder carcinoma. We evaluated the role of the interleukin-6/10 ratio as a prognostic marker of recurrence in patients with intermediate risk superficial bladder carcinoma., Materials and Methods: A total of 65 consecutive urological patients seen in the office, including 41 with intermediate risk superficial bladder carcinoma and 24 controls, were selected for this prospective study. Five urine samples for urinary cytology and interleukin analyses were collected from each subject at baseline, and 3, 6, 9 and 12 months after surgery, respectively. Interleukin-6 and 10 were determined in urine by the Quantikine solid phase interleukin-6 and 10 enzyme-linked immunosorbent assay, respectively. Sensitivity, specificity, and positive and negative predictive values of the method were calculated., Results: At baseline sample collection the interleukin-6/10 ratio was not statistically different between patients and controls (p = 0.58). Interleukin-6/10 was statistically different between patients with vs without recurrence 3 (0.009 vs 0.408), 6 (0.011 vs 0.268), 9 (0.012 vs 0.288) and 12 months (0.009 vs 0.302) after pre-transurethral bladder tumor resection (each p <0.001). Multivariate analysis indicated that interleukin-6/10 was an independent prognostic factor of recurrence (HR 3.62, 95% CI 2.80-4.92, p <0.001). Test sensitivity and specificity were 0.83% (95% CI 0.57-0.95) and 0.76% (95% CI 0.45-0.93), respectively., Conclusions: The current study highlights the feasible role of the interleukin-6/10 ratio for predicting intermediate risk superficial bladder carcinoma recurrence. However, clinical trials with a greater number of patients are needed to consider its use in clinical urological practice.

There has long been a need for biomarkers of disease activity in lupus nephritis (LN). Such markers ideally would be capable of detecting early sub-clinical disease and could be used to gauge response to therapy thus obviating the need for serial renal biopsies. Since urine can be readily obtained it lends itself as an obvious biological sample. Much of the focus has been on the measurement of urinary chemokines and cytokines in patients with LN. Elevations in urinary IL-6 and IL-10 had initially been reported to be associated with disease activity in LN but these markers have proven to be less reliable in larger studies. We and others have recently reported that MCP-1, a key chemokine involved in monocyte chemotaxis can be consistently found at high levels in the urine of patients with active LN. Moreover urinary MCP-1 levels decline with treatment of nephritis. In contrast urinary IL-8, a chemokine involved primarily in neutrophil chemotaxis is not a good predictor of disease activity in LN. Further longitudinal studies with larger numbers of patients are needed to determine the utility of urinary biomarkers such as MCP-1 which may act as surrogates of ongoing inflammation in LN.

Background: Previous studies have shown that messenger RNA (mRNA) expression of target genes is increased in the urinary sediment of patients with active lupus. We study the effect of immunosuppressive therapy on the urinary gene expression profile in patients with active lupus nephritis. Method. We recruited nine patients with active systemic lupus erythematosus (SLE) and renal disease, and required corticosteroid, with or without cytotoxic treatment. They were followed for 6 months, urine samples were collected at 0, 4, 12 and 24 weeks and gene expression profile was determined by polymerase chain reactions. The pattern of gene expression was compared to clinical parameters of therapeutic response., Results: Amongst the target genes studied, there was a progressive decline in the urinary expression of T-bet, interleukin (IL)-10, transforming growth factor-beta (TGF-beta), monocyte chemoattractant protein-1 (MCP-1), and interferon-gamma (IFN-gamma) after immunosuppressive treatment, although the change of IFN-gamma was not statistically significant. The time course of their urinary expression was parallel to the systemic activity as reflected by the systemic lupus erythematosus disease activity index (SLEDAI). Throughout the study period, the SLEDAI score correlated significantly with the expressions of IFN-gamma (r = 0.43, P = 0.009), T-bet (r = 0.40, P = 0.016), TGF-beta (r = 0.51, P = 0.002) and MCP-1 (r = 0.38, P = 0.022). The anti-double strand(anti-ds)DNA antibody titer correlated significantly with the expressions of IFN-gamma (r = 0.45, P = 0.009), T-bet (r = 0.37, P = 0.034), IL-10 (r = 0.59, P<0.001), TGF-beta (r = 0.44, P = 0.010) and MCP-1 (r = 0.49, P = 0.004). On the other hand, the expression level of IL-2, IL-4, IL-12, IL-18 and GATA-3 remained static throughout the study period., Conclusions: The mRNA expression of T-bet, IL-10, TGF-beta, MCP-1, and probably IFN-gamma in the urinary sediment of patients with active lupus nephritis improves with successful immunosuppressive therapy, and the change in gene expression profile is in phase with the clinical disease activity. Measurement of urinary mRNA expression of target genes may be a potential non-invasive tool for the monitoring of lupus disease activity.

Objective: To investigate the effects of interleukin-10 (IL-10) and IL-8 in the pathogenesis and diagnosis of chronic prostatitis (CP)., Methods: Twenty-nine different types of CP patients with complaints of low urinary duct symptom were selected at random, and the diagnosis of CP was established by inquiry of the history of prostatic disease, digital rectal examination of the prostate, and analysis of express prostatic secretions (EPS) for leukocytes. Bacterial infection of the prostate was detected by pre- and post-message test (PPMT) in some of the inflammatory CP patients. Quantitative evaluation of IL-10 and IL-8 levels in the limited voided bladder 3 (VB3) was performed by ELISA methods. Eleven healthy men without CP were chosen as control., Results: The level of IL-10 [(47.1 +/- 4.5) pg/ml] in VB3 in 8 patients with apparent clinical symptoms was significantly higher than in the 11 infertile males [(40.8 +/- 5.7) pg/ml] and the 21 patients with both infertility and asymptomatory inflammatory prostatitis (CP type IV) [(42.7 +/- 6.7) pg/ml], P < 0.05. The levels of IL-8 in the 8 patients with apparent clinical symptoms [(1386.2 +/- 852.6) pg/ml] and in the 13 patients with both infertility and asymptomatory inflammatory prostatitis (CP type IV) [(1203.8 +/- 807.8) pg/ml] were significantly higher than in the 7 healthy males [(412.1 +/- 217.2) pg/ml], P < 0.05., Conclusion: IL-10 and IL-8 had a very important role in etiology of CP, and could be detected in VB3 as well as in routine semen and EPS.

We evaluated the clinical significance of Th1(IL-2)/Th2(IL-10) urinary profiles during a weekly induction course lasting 6 weeks, followed by a weekly maintenance therapy schedule for 3 weeks. Urinary IL-2 and /IL-10 were measured by ELISA in 39 patients receiving BCG for superficial bladder cancer or carcinoma in situ. Measurements were made after each instillation of 81 mg of BCG Connaught (Immucyst) during the induction course and the 3-week maintenance therapy (given at 3, 6, 12, 18, 24, 30 and 36 months). Cytokine levels were correlated with the risk of recurrence, progression, leukocyturia and adverse events. Median follow-up was 35 months (range 7-72 months). Complete responses to BCG were obtained in 30 patients (77%); the remaining 9 patients relapsed (23%), and 4 of these patients progressed (10.2%). Failure to detect urinary IL-2 during BCG induction course and the first extended induction cycle (6+3 schedule) correlated with time to recurrence (p = 0.01) and progression (p = 0.01). During the extended induction cycle, the first instillation was associated with an IL-2 cytokine profile, whereas the second and third instillations were associated with a switch to an IL-10 cytokine profile. This switch was associated with leukocyturia (p = 0.0001) and adverse events (p = 0.03). The 6+3 schedule is associated with urinary IL-2 overproduction and improved recurrence- and progression-free survival. During the BCG extended induction cycle, the favorable IL-2 urinary cytokine pattern gradually switches to an IL-10 profile, suggesting that the schedule based on 3 weekly instillations may be unsuitable for some patients and that the dose and frequency of maintenance BCG instillations may be adapted to individual urinary cytokine levels., (Copyright 2003 Wiley-Liss, Inc.)

Cardiopulmonary bypass (CPB) significantly contributes to the plasma pro-inflammatory cytokine response at cardiac surgery. Complementary plasma and urinary anti-inflammatory cytokine responses have been described. The pro-inflammatory cytokines interleukin 8 (IL-8), tumour necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) have lower molecular weights than the anti-inflammatory cytokines interleukin 10 (IL-10), interleukin 1 receptor antagonist (IL-1ra) and TNF soluble receptor 2 (TNFsr2) and thus undergo glomerular filtration more readily. In vitro work suggests that proximal tubular cells are vulnerable to pro-inflammatory cytokine mediated injury. Accordingly, this study investigated the hypothesis that cardiac surgery without CPB would not have significant changes in plasma and urinary cytokines and proximal renal dysfunction. Eight patients undergoing coronary artery bypass grafting (CABG) without CPB were studied. Blood and urine samples were analysed for pro- and anti-inflammatory cytokines. Proximal tubular dysfunction was measured using urinary Nu-acetyl-beta-D-glucosaminidase (NAG)/creatinine and alpha(1)-microglobulin/creatinine ratios. Plasma IL-8, IL-10, IL-1ra and TNFsr2 were significantly elevated compared with baseline. Urinary IL-1ra and TNFsr2 were significantly elevated, as were urinary NAG/creatinine and alpha(1)-microglobulin/creatinine ratios. Two hours following revascularization, urinary IL-1ra correlated with urinary alpha(1)-microglobulin/creatinine ratios (P<0.05). As previously reported in CABG surgery with CPB, we now report that non-CPB cardiac surgery also has significant changes in plasma and urinary cytokine homeostasis and early proximal tubular injury. The correlation between urinary IL-1ra and alpha(1)-microglobulin/creatinine ratios is consistent with earlier suggestions of a mechanistic link between cytokine changes and proximal tubular dysfunction. The relative roles of CPB and non-CPB processes in producing inflammation still require definition., (Copyright 2002 Elsevier Science Ltd.)

Purpose: Interleukin (IL)-2 and interferon-gamma are released during T helper 1 lymphocyte responses, while IL-10 is released during T helper 2 responses. We evaluated the prognostic value of urinary IL-2, interferon-gamma and IL-10 levels in patients with superficial bladder cancer treated with bacillus Calmette-Guerin (BCG) instillation., Methods: Urinary IL-2, interferon-gamma and IL-10 were measured by enzyme-linked immunosorbent assay in 37 patients receiving BCG for stages Ta/T1 superficial bladder cancer, and carcinoma in situ. Measurements were made after instillations 5 and 6 during a course of 6 weekly instillations of 150 mg. BCG, Pasteur strain. Correlations of cytokine levels with the clinical outcome were evaluated using the log rank test., Results: Median followup was 29 months. Patients with urinary IL-2 less than 27 pg./micromol. creatinine were significantly more likely to have recurrences than those with higher values (log rank test p = 0.0009). Urinary IL-10 and interferon-gamma levels had no apparent impact on the risk of recurrence or progression., Conclusion: Urinary IL-2 levels may serve to identify patients at risk for bladder cancer recurrence after a single course of BCG and, thus, to tailor individual treatment.

Purpose: Interleukin (IL)-2 and interferon-gamma are released during T helper 1 lymphocyte responses and IL-10 is released during T helper 2 lymphocyte responses. We have previously reported that a T helper 1 lymphocyte urinary cytokine profile is associated with a favorable prognosis after bacillus Calmette-Guerin (BCG) treatment. We evaluated the T helper 1/2 lymphocyte cytokine profiles during courses 1 and 2 of 6 weekly BCG instillations., Materials and Methods: Urinary interferon-gamma, IL-2 and IL-10 were measured by enzyme-linked immunosorbent assay after each of 6 weekly instillations of 150 mg. BCG, Pasteur strain, in 19 patients with superficial stages Ta and T1 bladder cancer, and carcinoma in situ. The 11 patients who did not respond to course 1 were re-treated according to the same schedule and reevaluated., Results: During course 1 interferon-gamma was higher than during course 2 (p <0.001), which was associated with nonrecurrence (p <0.001). In contrast, IL-2 cytokine was higher after course 2 (p <0.01), which was associated with a BCG response (p = 0.01). Interferon-gamma and IL-10 correlated during courses 1 and 2 (p = 0.04 and 0.0004, respectively). We distinguished groups 1-immediate T helper 1 lymphocyte profile consisting of responders to course 1 with high interferon-gamma, IL-2 and IL-10, 2-delayed T helper 1 lymphocyte profile consisting of responders to course 2 with early high IL-2 and 3-consisting of nonresponders to the 2 courses with low interferon-gamma, IL-2 and IL-10., Conclusions: A T helper 1 lymphocyte urinary cytokine profile was associated with a clinical response to BCG. A repeat BCG course induces a favorable immune response in a subset of patients, suggesting that maintenance therapy may be beneficial.

Background: Acute rejection and urinary tract infection (UTI) both increase nitric oxide synthase (NOS) activity in urine from renal transplant patients. Also, with rejection, a regulatory interplay between nitric oxide (NO) and cytokines has been suggested. Thus, measurement of the temporal changes of NOS products and cytokines in urine will provide a strategy for the diagnosis of acute rejection and for its differentiation from UTI., Methods: Soluble interleukins (ILs) and NOS-related products, cyclic GMP (cGMP), nitrate, and nitrite were measured in 192 urine samples consecutively collected from 13 patients within the first three months of transplantation. Sixty-seven additional urine specimens were collected randomly from 24 patients for follow-up analysis of the nitrate test., Results: Among patients who experienced rejection, the percentage (%) binding of IL-2 increased within the first five days (P = 0.0004) after transplantation and one to five days prior to the clinical diagnosis (dx) of rejection (P = 0.02). Tumor necrosis factor-alpha, IL-6, and IL-8 increased at the time of rejection dx (P < or = 0.01). With UTI, IL-2 (P = 0.01) decreased one to five days prior to dx, and IL-10 (P = 0.003) increased one to five days after dx. Although cGMP and nitrate are dependent variables, cGMP increased (P < or =0.0009) with both rejection and UTI, and nitrate increased (P = 0.0001) with rejection and decreased (P = 0.0001) with UTI. Prior to formal dx (1 to 5 days), urine nitrate clearly differentiated rejection (3004 to 7451 micromol/L) from UTI (90 to 885 micromol/L) and controls (1059 to 3235 micromol/L). The additional 67 urines demonstrated that the sensitivity of the nitrate test for rejection and UTI was 100%., Conclusions: In renal transplant patients, specific temporal changes in urine cytokine levels do occur with acute rejection and UTI, but urine nitrate levels are the most precise at differentiating rejection from UTI.

Background: Cytokines and cytokine receptors are involved in the systemic and local inflammatory response in patients with urinary tract infections., Methods: We examined urine and serum concentrations of soluble IL-6 receptor (sIL-6R), IL-10 and granulocyte colony-stimulating factor (G-CSF) in 29 women with acute pyelonephritis caused by Escherichia coli 2 weeks after the infection, during the subsequent episode of cystitis or asymptomatic bacteriuria and also later when the same patients were free from bacteriuria. Concentrations of sIL-6R, IL-10 and G-CSF were related to the expression of five virulence markers of E. coli and to glomerular filtration rate (GFR) after pyelonephritis., Results: On admission because of acute pyelonephritis the serum concentration of sIL-6R was similar to that of 12 healthy controls. Two weeks after the infection when all patients had received antibiotic treatment, the serum concentration of sIL-6R was significantly higher compared to that on admission (p < 0.001) and also higher compared to healthy controls (p = 0.001). Patients with increased concentrations of sIL-6R in serum 2 weeks after infection had significantly lower GFR at follow-up (p < 0.05). Patients with acute pyelonephritis had higher concentrations of G-CSF and IL-10 in serum compared to healthy subjects (p < 0.001 and p = 0.06, respectively). G-CSF in serum was higher in patients infected by E. coli producing cytotoxic necrotizing factor (p < 0.05). Patients infected by strains producing hemolysin had lower concentrations of sIL-6R (p < 0.001). Patients with detectable levels of the anti-inflammatory cytokine IL-10 in serum had significantly higher concentrations of IL-6 and the soluble tumor necrosis factor receptors I and II in serum as compared to patients in whom IL-10 was not detectable (p < 0.001, p = 0.001 and p < 0.05, respectively., Conclusion: These investigations, together with our previous findings summarized in this paper, contribute to an increased understanding of the local and systemic inflammatory response arising in response to acute pyelonephritis.

The antiinflammatory cytokine response during urosepsis was determined by measurement of concentrations of soluble tumor necrosis factor receptor (sTNFR) types I and II, interleukin 1 receptor antagonist (IL-1ra), soluble IL-1 receptor type II (sIL-1RII), and interleukin 10 in sera and urine of 30 patients with culture-proven urinary tract infections before and 4, 24, 48, and 72 h after initiation of antibiotic therapy and in 20 healthy individuals. In serum, the levels of sTNFR types I and II, IL-1ra, and IL-10 were higher in patients than in controls. In urine, only sTNFR type I and II levels were elevated in patients. The ratios of concentrations of both types of sTNFR in urine to concentrations in serum were higher in patients than in controls. These findings indicate that during urosepsis, the antiinflammatory cytokine response is generated predominantly at the systemic level.

Typically, ovarian cancer remains restricted to the peritoneal cavity. Because of this unique localization, the study of ovarian cancer is particularly suitable for immune analysis and for the development of immunotherapy. Here we report that peritoneal fluid from patients with ovarian or other intra-abdominal cancers contained significantly elevated levels of interleukin 10 (IL-10) (542 +/- 77 pg/ml, N = 35), compared with peritoneal fluid from patients with benign gynecological conditions (34.2 +/- 7.5 pg/ml, N = 63) (P < 0.001). Peritoneal fluid IL-10 levels did not correlate with histology, tumor stage, grade, or prognosis. IL-10 levels were also elevated in the serum of patients with intra-abdominal cancer (1353 +/- 906, N = 8). Established ovarian cancer cell lines (N = 5) did not produce any detectable IL-10. Investigation of the cell surface phenotype of the cells in the peritoneal cavity indicated the presence of significant amounts of activated immune cells. The presence of cytokines such as IL-10 in the peritoneal cavity of ovarian cancer bearing patients could be important in the growth and development of cancer, more specifically, in relation to host immune responsiveness.