Urinary Interleukin-6 Research Articles

Изменения иммунитета и микроциркуляции в почках на фоне лечения гнойного пиелонефрита

Изменения иммунитета и микроциркуляции в почках на фоне лечения гнойного пиелонефрита

Prognostic Utility of KDIGO Urine Output Criteria After Cardiac Surgery

Kidney Disease: Improving Global Outcomes (KDIGO) guidelines include assessment of creatinine and urine output to identify acute kidney injury (AKI). Whether urine output is an accurate indicator of AKI after cardiac surgery, however, is unclear. The authors' goal was to examine whether cardiac surgery patients who fulfilled criteria for AKI by KDIGO urine output criteria also demonstrated kidney injury by elevated creatinine, other kidney biomarkers, or had worse clinical outcomes. Secondary analysis of prospectively collected data from a clinical trial, "6% Hydroxyethyl starch 130/0.4 in Cardiac Surgery (NCT02192502)." Academic, quaternary care hospital. Patients undergoing elective aortic valve replacement INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: One hundred forty-one patients were classified into AKI stage by KDIGO urine output criteria within 24 hours after surgery. Kidney biomarkers (serum creatinine, urinary neutrophil gelatinase-associated lipocalin [NGAL], urinary interleukin-18 [IL-18]) and hospital and intensive care unit length of stay were analyzed across AKI stages. Urine output criteria classified four times as many patients with AKI than creatinine criteria (95 [67%] v 21 [15%]). Most patients meeting KDIGO urine output criteria for AKI postoperatively did not satisfy KDIGO creatinine criteria for AKI within one week (77 of 95 [81%]) or six-to-12 months (27 of 29 [93%]). Higher AKI stage assessed by urine output was not associated with higher NGAL, IL-18, or longer hospital or intensive care unit stays. Acute kidney injury classified by KDIGO urine output criteria was not associated with other biomarkers of kidney injury or worse patient outcomes. These data suggested that KDIGO urine output criteria after cardiac surgery may overclassify AKI stage; further research is needed.

Relationships between inflammation, hemodynamic function and RAAS in longstanding type 1 diabetes and diabetic kidney disease.

The renin angiotensin aldosterone system (RAAS) is associated with renal disease and inflammation in a diabetes setting, however, little is known about the implicated mechanisms in individuals with long standing diabetes. Accordingly, our aim was to perform an observational study to quantify urinary excretion of inflammatory biomarkers in participants with long standing type 1 diabetes (T1D) (with and without diabetic kidney disease [DKD]) and controls, at baseline and in response to RAAS activation. GFRINULIN, ERPFPAH, and 42 urine inflammatory biomarkers were measured in 74 participants with T1D for ≥50 years (21 with DKD and 44 without DKD [DKD resistors]) and 73 healthy controls. Additionally, inflammatory biomarkers were measured before and after an angiotensin II infusion (ANGII, 1 ng∙kg-1∙min-1). Significantly lower urinary excretion of cytokines (IL-18, IL-1RA, IL-8), chemokines (MCP1, RANTES) and growth factors (TGF-α, PDGFAA, PDGFBB, VEGF-A) was observed in participants with T1D at baseline compared to controls. Urinary IL-6 was higher in DKD than in DKD resistors in an exploratory analysis unadjusted for multiple comparisons. In T1D only, lower GFRINULIN correlated with greater excretion of proinflammatory biomarkers (IL-18, IP-10, & RANTES), growth factors (PDGF-AA & VEGFAA), and chemokines (eotaxin & MCP-1). ANGII increased 31 of 42 inflammatory biomarkers in T1D vs controls (p < 0.05), regardless of DKD resistor status. In conclusion, lower GFR and intra-renal RAAS activation were associated with increased inflammation even after longstanding T1D. The increased urinary IL-6 in patients with DKD requires further investigation to determine whether IL-6 is a candidate protective biomarker for prognostication or targeted therapy in DKD.

Acute kidney damage by PM2.5 exposure in a rat model

PM2.5 exposure is associated with a glomerular filtration rate (GFR) reduction, and renal tissue damage. The goal of this study was demonstrate the acute effect of PM2.5 on the kidney. Male rats were acutely exposed to PM2.5 or filtered air. Blood pressure was mesure and early kidney biomarkers were evaluated in serum and urine samples, and also IL-1β, IL-6 and TNFα were determined. Oxidative biomarkers, angiotensin/bradykinin-related proteins, KIM-1, IL-6 and histology were determined. Blood pressure, GFR, and early kidney damage biomarkers increase together with oxidative biomarkers and angiotensin/bradykinin endocrine-related proteins increased after exposure to PM2.5. Urinary IL-6 increased after exposure to PM2.5, whereas in kidney cortex decreased. Histological changes were observed and accompanied by the induction of KIM-1. Acute exposure to PM2.5 not decline kidney function. However, it can induce early kidney damage biomarkers, oxidative stress, inflammation and angiotensin mediators, which perhabs culminates in a lose of renal function.

Using urinary Interleukin-18 as a potential marker for early detection of acute kidney injury in intensive care unit.

Acute kidney injury (AKI) is a potentially life-threatening condition. The injury involves the generation of inflammatory mediators which contribute to the recruitment of leukocytes to the site of inflammation. As those inflammatory mediators are secreted directly into the urine, their detection in urine could serve as potential biomarkers for the diagnosis of early kidney injury. This is a prospective cross-sectional descriptive study. Urinary samples were collected from 170 subjects who were admitted to intensive care unit (ICU) at Alkafeel Super Speciality Hospital from September 2017 to June 2018. They were tested for urinary interleukin-18 (IL-18). Among 98 patients, 20 were excluded depending on exclusion criteria. Seventy-two cases in the control group were included. The urine samples were collected at 24, 48, and 72 h after admission to ICU. AKI was diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The incidence rate of AKI among 78 patients who were admitted to ICU was 38.46%. Most of the patients with AKI belonged to stage 1 (80%) based on KDIGO guidelines2012. Urinary IL-18 levels were significantly higher (P <0.0001) in the AKI group in comparison with the non-AKI group. The result of receiver operating characteristic analysis showed that the higher area under the curve for urinary IL-18 was 0.946 measured at 24 h before development of AKI (P <0.000), with 87.5% sensitivity and 94.4% specificity. In addition, there was no significant difference of urinary IL-18 levels between the different causes of AKI. The results of the study indicate that urinary IL-18 has an excellent performance in predicting AKI in ICU patients.

High level of interleukin-10 in serum after therapy is characteristic of prostate carcinoma patients with high Gleason score, high tumor volume and present peritumoral infiltration

Background/Aim. Recent data imply the significance of certain cytokines in the appearance and development of prostate cancer (PC), as well as their association with pathohistological and/or clinical characteristics of PC. The aim of this study was to examine the relationship between the IL-10 concentration with histopathological and clinical characteristics of PC patients. Methods. IL-10 concentration was determined in serum, urine and prostate massage secret (pms) samples of 88 CP patients (initially and after therapy), 20 benign prostatic hyperplasia (BPH) patients and 15 healthy controls. Results. Compared to BPH and control groups, PC patients had the highest average serum IL-10 concentration. Interestingly, BPH patients demonstrated the highest concentration of IL-6 in urine and pms samples. Also, patients with G3 gradus and with the highest Gleason score (4 + 4) demonstrated the highest IL-10 serum level. PC patients without any histopathological sign of tumor invasion had a significantly increased serum IL-10, either before or after the therapy, compared to the patient group with evident invasion of tumor cells. The therapy induced different IL-10 profile in serum and urine samples. After the therapy, there was a clear significant IL-10 increase in serum of patients with unfavorable Gleason score (4 + 4), with present infiltration of tumor cells in peritumoral tissue (lymphatic, vascular and combined) and in patients with high tumor volume. Conclusion. PC patients without any histopathological signs of tumor invasion before the therapy have significantly increased serum IL-10 concentration compared to those with the signs of tumor invasion. There is a clear dissociation of IL-10 values between a serum sample and local, urine and pms samples from a particular patient. After the therapy, high IL-10 serum concentration is present only in patients with high Gleason score, pre-sent infiltration of peritumoral tissue and high tumor volume.

Plasma neutrophil gelatinase-associated lipocalin and Interleukin-18 as predictors of acute kidney injury in renal transplant recipients: A pilot study.

Urine neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL- 18) have shown promise for predicting renal graft recovery. However, urinary flow rate variations may cause variable biomarker dilution. Plasma NGAL and IL-18 may form a biomarker panel that may help predict delayed graft function and slow graft function (SGF) in renal transplant recipients within the first two postoperative days earlier than serum creatinine. There are only a few studies in the literature using plasma NGAL for predicting renal graft recovery. Hence, we planned this study. This observational single-center, prospective cohort study was conducted in renal transplant recipients above 18 years of age. In 22 consecutive renal transplant recipients, we collected ethylenediaminetetraacetic acid-plasma samples 1 h before surgery and subsequently at 6 h, 24 h, and 48 h after surgery for NGAL and IL-18 by sandwich enzyme-linked immuno-sorbent assay technique. Serum creatinine was measured as a part of routine transplant protocol. In renal transplant recipients, neither serum levels of NGAL and IL-18 nor their trends could reliably predict SGF. The only significant correlation existed between serum creatinine at day 2 and IL-18 at day 2 with P = 0.023. Serum NGAL did not correlate with serum creatinine in this setting of renal transplantation. Patients with immediate graft function had a greater percentage decrease of creatinine at day 1 and day 2 (P = 0.002 and 0.001) The percentage change in IL-18 at 24 h and 48 h after transplant from baseline could predict the occurrence of early graft loss (EGL) (P = 0.05, 0.04). The cutoffs were -4.12% at day 1 and +3.39% at day 2 with area under receiver operator characteristics of 0.82 and 0.83, respectively. The percentage change in IL-18 may be a useful marker of EGL in renal transplant recipients. Serum NGAL and creatinine were not able to predict EGL.

Association of Non-Steroidal Anti-Inflammatory Drugs with Kidney Health in Ambulatory Older Adults.

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause kidney injury, especially in older adults. However, previously reported associations between NSAID use and kidney health outcomes are inconsistent and limited by reliance on serum creatinine-based GFR estimates. This analysis investigated the association of NSAID use with kidney damage in older adults using multiple kidney health measures. Cross-sectional and longitudinal analyses. Multicenter, community-based cohort. Two thousand nine hundred and ninty nine older adults in the Health ABC Study. A subcohort (n = 500) was randomly selected for additional biomarker measurements. Prescription and over-the-counter NSAID use ascertained by self-report. Baseline estimated glomerular filtration rate (eGFR) by cystatin C (cysC), urine albumin-to-creatinine ratio (ACR), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) were measured in 2,999 participants; alpha-1 microglobulin (α1m), neutrophil gelatinase-associated lipocalin (NGAL), propeptide type III procollagen (PIIINP), and uromodulin (UMOD) were measured in 500 participants. GFR was estimated three times over 10 years and expressed as percent change per year. Participants had a mean age of 74 years, 51% were female, and 41% African-American. No eGFR differences were detected between NSAID users (n = 655) and non-users (n = 2,344) at baseline (72 ml/min/1.73 m2 in both groups). Compared to non-users, NSAID users had lower adjusted odds of having ACR greater than 30 mg/g (0.67; 95% confidence interval (CI) = 0.51-0.89) and lower mean urine IL-18 concentration at baseline (-11%; 95% CI = -4% to -18%), but similar mean KIM-1 (5%; 95% CI = -5% to 14%). No significant differences in baseline concentrations of the remaining urine biomarkers were detected. NSAID users and non-users did not differ significantly in the rate of eGFR decline (-2.2% vs -2.3% per year). Self-reported NSAID use was not associated with kidney dysfunction or injury based on multiple measures, raising the possibility of NSAID use without kidney harm in ambulatory older adults. More research is needed to define safe patterns of NSAID consumption.

Urine interleukin-9 and tumor necrosis factor-α for prognosis of human acute interstitial nephritis

We previously demonstrated that urine interleukin (IL)-9 and tumor necrosis factor (TNF)-α can distinguish acute interstitial nephritis (AIN) from other causes of acute kidney injury. Here we evaluated the role of these biomarkers to prognosticate kidney function in patients with AIN. In a cohort of participants with biopsy-proven, adjudicated AIN, we tested the association of histological features and urine biomarkers (IL-9 and TNF-α) with estimated glomerular filtration rate measured 6 months after diagnosis (6 m-eGFR) controlling for eGFR before AIN and albuminuria. We also evaluated subgroups in whom corticosteroid use was associated with 6 m-eGFR. In the 51 (93%) of the 55 participants with complete data, median (interquartile range) eGFR before and 6 m after AIN were 41 (27-69) and 28 (13-47) mL/min/1.73 m2, respectively. Patients with higher severity of interstitial fibrosis had lower 6 m-eGFR, whereas those with higher tubulointerstitial infiltrate had higher 6 m-eGFR. IL-9 levels were associated with lower 6 m-eGFR only in the subset of patients who did not receive corticosteroids [6m-eGFR per doubling of IL-9, -6.0 (-9.4 to -2.6) mL/min/1.73 m2]. Corticosteroid use was associated with higher 6 m-eGFR [20.9 (0.2, 41.6) mL/min/1.73 m2] only in those with urine IL-9 above the median (>0.66 ng/g) but not in others. Urine IL-9 was associated with lower 6 m-eGFR only in participants not treated with corticosteroids. Corticosteroid use was associated with higher 6 m-eGFR in those with high urine IL-9. These findings provide a framework for IL-9-guided clinical trials to test efficacy of immunosuppressive therapy in patients with AIN.

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

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

Urine biomarkers for monitoring acute kidney injury in premature infants.

BackgroundPremature infants are at high risk for acute kidney injury (AKI). Serum creatinine (Cr) has limitations for evaluating kidney function in premature infants. We evaluated whether urine biomarkers could be used to monitor AKI in premature infants.MethodsA prospective cohort study was conducted among infants born at < 37 weeks. Urine biomarkers and serum Cr were measured on postnatal days 1, 3, 5, 7, 10, and 14. Infants were divided into 3 groups according to gestational age (GA); < 28, 28 to < 32 and 32 to < 37 weeks.ResultsAKI occurred in 17 of 83 (20.5%) recruited infants at a median age of 7 (interquartile range 5–10) days. While the most common cause of AKI was hemodynamically significant patent ductus arteriosus (53.8%) in infants of GA < 28 weeks, necrotizing enterocolitis was the leading cause (50.0%) in infants of GA 28 to < 32 weeks. Urinary levels of neutrophil-gelatinase-associated lipocalin/Cr were higher and epidermal growth factor/Cr were lower in AKI group before the onset of AKI in infants of GA < 28 weeks. In infants of GA 28 to < 32 weeks, urinary interleukin-8/Cr levels were higher in AKI group at approximately the time of AKI onset.ConclusionSeveral urine biomarkers were significantly different between AKI and no AKI groups, and some had changed before the onset of AKI. These groups were distinct according to causative factors of AKI and GA. Urine biomarkers could be useful for monitoring the development of AKI in premature infants.

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

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

Utility of Urine Interleukines in Children with Vesicoureteral Reflux and Renal Parenchymal Damage.

Vesicoureteral reflux (VUR) is the most common risk factor of urinary tract infection in children. Currently, diagnosis of VUR depends on invasive imaging studies, with a high radiologic burden. Therefore, different biomarkers have been introduced for the evaluation of these patients. The objective of this study was to identify alteration of urinary interleukins (ILs) excretion in children with primary VUR and renal parenchymal damage, for further clinical application. Urinary concentrations of IL-1α, IL-1β, IL-6, and IL-8 were evaluated in 34 children with VUR (cases) and 36 without VUR (control), during 2018-2019. Urinary concentrations of IL-1, IL-1, IL-6 and IL-8 were measured, using polyclonal antibody ELISA kit, and standardized to urine creatinine (Cr). Patients with infectious or inflammatory disorders, urolithiasis, immune deficiency, acute or chronic kidney disease, and secondary VUR were excluded from the study. Mean age of cases (36.00 ± 27.66) had no significant difference with the control (32.86±29.31) group (p=0.44). The majority of patients had moderate VUR (58.8%), followed by severe (35.3%) and mild (5.9%) grades. Urinary concentration of all ILs/Cr were significantly higher in patients with VUR, compared with those without VUR. There was no significant correlation between urine ILs/Cr with age, gender, serum electrolytes, urine specific gravity, renal ultrasound, laterality or severity of VUR, and DMSA renal scan. All urine ILs/Cr had acceptable sensitivity and accuracy for workup of children with primary VUR. Urine IL-1α, IL-1β, IL-6 and IL-8/Cr were sensitive and accurate additionary screening biomarkers in children with primary VUR.

Correlation between the level of urine interleukin-6 with microalbuminuria in Systemic Lupus Erythematosus (SLE) patients at Sanglah General Hospital, Bali, Indonesia

Background: Lupus Nephritis (LN) is one of the serious manifestations of SLE. Because of its role in the pathogenesis of LN, IL-6 is likely to be a potential marker, whereas for diagnosing kidney involvement at the subclinical stage, microalbuminuria can be examined. Therefore, early detection of kidney damage in SLE is needed to prevent the progression of NL to permanent kidney failure. This study aims to evaluate the relationship between IL-6 levels and microalbuminuria in SLE patients at Sanglah General Hospital Bali.Methods: This study used a cross-sectional analytic design, carried out in Sanglah General Hospital on SLE patients, conducted in May until July 2019. Blood and urine samples were taken to obtain the data needed to measure the Mex-SLEDAI score. Cytokine evaluation is done by quantitative examination using enzyme-linked immunosorbent assay (ELISA). Chi-square analysis was done using SPSS version 24 for Windows.Results: The results of the study were 85 subjects with SLE (94.1% women). The median age is 35 years (18-61 years), and the median duration of illness is three years (0.4-18 years). Most of the patients were in inactive clinical condition, 54 patients (63.53%) and laboratory results were still in the normal range. Steroids (94.1%) are the most widely used therapeutic options. Urine IL-6 levels were obtained with a mean of 0.41±0.21 pg/ml, while microalbuminuria levels were obtained with a median of 20 (0-100) mg/L. The results of data analysis stated that there was no significant relationship between urine IL-6 levels and microalbuminuria in SLE (p = 0.972).Conclusion: In this study, there was no significant relationship between urine IL-6 levels and microalbuminuria.

Prediction of Acute Kidney Injury in Critically-Ill Pediatric Patients Admitted to PICU: The Role of Serum Cystatin C And Serum Interleukin-18

Objectives: We conducted this study to assess the sensitivity and specificity of serum cystatin C (sCysC) and serum interleukin-18 (IL-18) in comparison with serum creatinine and serum urea for early detection of acute kidney injury (AKI) in critically-ill pediatric patients admitted to the pediatric intensive care unit (PICU). Methods: This was an observational case-control study enrolled 61 patients admitted in PICU divided into two groups (the case group 30 patients with proposed AKI and the control group 31 control individuals). After complete clinical evaluation, electrolyte profile, including Na and K besides the biomarkers assay of serum creatinine, urea, sCysC , and IL-18 were measured at the first day of admission and after three days. Results: Urea and creatinine were increased at admission in only three patients and two patients, respectively, while it dramatically increased in 25 patients in both urea and creatinine separately on the third day of admission. sCysC and sIL-18 showed a high diagnostic ability for detecting AKI at admission with AUCs of 0.877 and 0.819 respectively. Supportingnly, sCysC and IL-18 were significantly higher in AKI group compared to the control group. Conclusions: sCysC and serum IL-18 proved their accuracy in prediction of AKI in patients admitted to the PICU. Their diagnostic ability was superior to serum creatinine, serum urea, and even urinary IL-18 and CysC.

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

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

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

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

Effects of Monomeric and Oligomeric Flavanols on Kidney Function, Inflammation and Oxidative Stress in Runners: A Randomized Double-Blind Pilot Study.

Nonsteroidal anti-inflammatory drugs are frequently used by athletes in order to prevent musculoskeletal pain and improve performance. In combination with strenuous exercise, they can contribute to a reduction of renal blood flow and promote development of kidney damage. We aimed to investigate whether monomeric and oligomeric flavanols (MOF) could reduce the severity of kidney injuries associated with the intake of 400-mg ibuprofen followed by the completion of a half-marathon in recreational athletes. In this double-blind, randomized study, the original MOF blend of extracts from grape seeds (Vitis vinifera L.) and pine bark (Pinus pinaster L.) or placebo were taken for 14 days preceding the ibuprofen/half-marathon. Urine samples were collected before and after the ibuprofen/half-marathon, and biomarkers of kidney injury, inflammation and oxidative stress were assessed. Intake of MOF significantly reduced the incidence of post-race hematuria (p = 0.0004) and lowered concentrations of interleukin (IL)-6 in the urine (p = 0.032). Urinary neutrophil-associated lipocalin, creatine, albumin, IL-8 and malondialdehyde tended to decrease. The supplementation with MOF in recreational runners appears to safely preserve kidney function, reduce inflammation and promote antioxidant defense during strenuous exercise and intake of a single dose of ibuprofen.

No Effect of New Zealand Blackcurrant Extract on Recovery of Muscle Damage Following Running a Half-Marathon.

New Zealand blackcurrant (NZBC) contains anthocyanins, known to moderate blood flow and display anti-inflammatory properties that may improve recovery from exercise-induced muscle damage. The authors examined whether NZBC extract supplementation enhances recovery from exercise-induced muscle damage after a half-marathon race. Following a randomized, double-blind, independent groups design, 20 (eight women) recreational runners (age 30 ± 6 years, height 1.73 ± 0.74m, body mass 68.5 ± 7.8kg, half-marathon finishing time 1:56:33 ± 0:18:08hr:min:s) ingested either two 300-mg/day capsules of NZBC extract (CurraNZ™) or a visually matched placebo, for 7 days prior to and 2 days following a half-marathon. Countermovement jump performance variables, urine interleukin-6, and perceived muscle soreness and fatigue were measured pre, post, and at 24 and 48hr after the half-marathon and analyzed using a mixed linear model with statistical significance set a priori at p < .05. The countermovement jump performance variables were reduced immediately post-half-marathon (p < .05), with all returning to pre-half-marathon levels by 48hr, except the concentric and eccentric peak force and eccentric duration, with no difference in response between groups (p > .05). Urine interleukin-6 increased 48-hr post-half-marathon in the NZBC group only (p < .01) and remained unchanged compared with pre-half-marathon levels in the placebo group (p > .05). Perceived muscle soreness and fatigue increased immediately post-half-marathon (p < .01) and returned to pre-half-marathon levels by 48hr, with no difference between groups (p > .05). Supplementation with NZBC extract had no effect on the recovery of countermovement jump variables and perceptions of muscle soreness or fatigue following a half-marathon in recreational runners.

Trans IL-6 signaling does not appear to play a role in renal scarring after urinary tract infection

While inflammation is an important innate defense mechanism against infection, it can also lead to local tissue damage. The trans signaling pathway of interleukin (IL)-6 is a known mediator of inflammation. We hypothesized that the trans IL-6 signaling pathway is associated with the development of post febrile urinary tract infection (UTI) renal scarring. To compare soluble regulators of trans IL-6 signaling between patients with a history of febrile UTI who do or do not have renal scarring. After IRB-approval, we collected urine samples in pediatric patients with a history of febrile (≥38°C) UTI (urine culture >50K uropathogen) with documented presence or absence of renal scarring on imaging. Samples were collected at a time when patients were not actively infected. Enzyme-linked immunosorbent assays were performed on samples for markers of trans IL-6 signaling: IL-6, soluble (s) IL-6 receptor (R), and soluble (s)gp130, a buffer in trans IL-6 signaling. Values were normalized to urine creatinine. Results were analyzed by t-test or Mann-Whitney U. Spearman rank correlation was used. A p-value of <0.05 was considered significant. A total of 50 urines from patients with a history of febrile UTI were collected: 23 with and 27 without scarring. There was no difference between groups regarding age or gender. There was no significant difference in urine IL-6, sIL-6R, or sgp130 between those with and without scarring (Figure). While IL-6 values significantly correlated with sIL-6R and sgp130 in those without renal scarring, IL-6 did not correlate with sgp130 in those with scarring. Ratios of IL-6 to sgp130 and sIL-6R to sgp130 were not different between groups. The inflammatory response generated in response to infection is believed to be largely responsible for the development of renal scarring after UTI. IL-6 is a cytokine known to be induced during UTI with a pro-inflammatory pathway, known as trans signaling. This study investigated for differences in markers of trans IL-6 signaling between patients with a history of febrile UTI with and without renal scarring. There was no significant difference between the absolute values or ratio of these markers between groups. Markers of trans IL-6 signaling are not different between individuals with a history of febrile UTI with and without renal scarring in the non-acute setting.