interleukin-8 and Pyelonephritis

Urinary tract infection (UTI) is common among pediatric population. Pyelonephritis, especially in young infants, is associated with a significant morbidity. Usually, clinical manifestations, laboratory findings, and imaging are used to differentiate between lower and upper UTI. Lack of specific clinical findings and commonly used nonspecific blood indices are important hamper differentiation between lower and upper UTI in early stages. Imaging techniques are neither cost benefit nor safe for detection of UTI. Recent efforts have focused on characterization of novel serum and urinary biomarkers for early detection of acute pyelonephritis in children. It seems that urinary NGAL, NAG, TNF-α and IL-8 may be used as novel markers for early diagnosis of acute pyelonephritis in children.

Topics: Acute Disease; beta-N-Acetyl-Galactosaminidase; Biomarkers; Child; Child, Preschool; Early Diagnosis; Humans; Infant; Interleukin-8; Lipocalin-2; Pyelonephritis; Tumor Necrosis Factor-alpha; Urinary Tract Infections

One of the most serious complications of acute febrilepyelonephritis in children is the development of renal scar. Thisstudy aimed to investigate the effect of dexamethasone on urinarycytokine levels and renal scar in children with acute pyelonephritis.. In a double-blind randomized clinical trial, 60 childrenaged 3 months to 12 years with acute febrile pyelonephritis enrolled.The experimental group was treated with a combination of antibioticand dexamethasone, and the control group underwent treatmentwith antibiotic and placebo. The urinary levels of interleukin -6(UIL-6) and -8 (UIL-8) were measured before treatment as baselineand were repeated four days later.. 52 cases (23 patients with mean age of 34.19 ± 30.82 monthsin the dexamethasone group, and 29 patients with mean age of50.55 ± 44.41 months in the control group) completed the study. Inthe control group, the UIL-6 and UIL-8 level became significantlylower after four days treatment (P < .05). In the dexamethasonegroup, there was a statistically significant difference between bothUIL-6 and UIL-8 levels before and after treatment (P < .05). Inpatients who had scar on DMSA scan, the mean UIL-8 and UIL-6levels were significantly high before and after treatment.. Results of this study showed that dexamethasone plusantibiotic have no clear superiority to antibiotic therapy alone indecreasing inflammatory cytokines and scar formation. We foundout that patients with scar had sustained high levels of biomarkersbefore and after treatment.

Topics: Acute Disease; Child; Child, Preschool; Cicatrix; Cytokines; Dexamethasone; Double-Blind Method; Female; Humans; Infant; Interleukin-6; Interleukin-8; Kidney; Male; Pyelonephritis; Radionuclide Imaging

Neutrophil accumulation in the graft kidney is a feature of cellular rejection and bacterial infection. The cellular infiltration is mediated by the local production of chemoattractant factors. The aim of the study was to analyze levels of IL-8 in renal graft recipients during and after episodes of acute renal rejection and urinary tract infection (UTI). A total of 50 renal graft recipients, including 10 with acute graft rejection (Group I) and 20 with UTI (Group II) were studied. Urine and serum levels of IL-8 were determined in patients of Group I before and after 7 days of antirejection therapy and in patients of Group II before and after 2 weeks of antimicrobial therapy. Results were compared with group of 20 patients with stable renal function and a group of 25 healthy people. IL-8 was determined by ELISA technique. The level of IL-8 in urine (uIL-8) was elevated in patients with acute graft rejection and uIL-8 decreased after antirejection treatment (772 +/- 241 pg/mg cr. vs 140 +/- 50 pg/mg cr.; p < 0.01). In 13 patients UTI was asymptomatic and 6 patients had an acute pyelonephritis. The level of uIL-8 was elevated in all patients with UTI and decreased after antimicrobial therapy. Levels of uIL-8 during acute pyelonephritis were significantly higher (p < 0.01) than in patients with asymptomatic bacteriuria (2582 +/- 950 pg/mg cr. vs 804 +/- 225 pg/mg cr.) Urine levels of IL-8 were lower in patients infected by Gram-positive Cocci as compared to patients infected by Gram-negative organisms. Patients with higher concentrations of serum creatinine during UTI had high urine levels of IL-8. Serum levels of IL-8 in patients of Group I and Group II were comparable with patients with stable graft function although they were higher than in control group. Elevated urinary secretion of IL-8 in acute rejection and UTI suggests a role of IL-8-neutrophiles system in in the pathogenesis in both inflammatory complications after kidney transplantation. Urine level of IL-8 was correlated with clinical symptoms of UTI.

Topics: Adult; Aged; Bacterial Infections; Bacteriuria; Biomarkers; Creatinine; Female; Graft Rejection; Humans; Interleukin-8; Kidney Transplantation; Male; Middle Aged; Neutrophil Activation; Pyelonephritis; Urinary Tract Infections

The objective of this study was to probe the effect and mechanism of Szechwan Lovage Rhizome (Chuanxiong, CX) extract on renal function (RF) and inflammatory responses (IRs) in acute pyelonephritis (APN) rats infected with Escherichia coli (E. coli). Fifteen SD rats were randomized to intervention, model and control groups. Rats in the control were fed normally without treatment, rats in the APN model were infected with E. coli, and rats in the intervention group were intragastrically administered CX extract after infection with E. coli. HE staining detected pathological changes in the kidney tissues in rats. Levels of renal function indexes and inflammatory factors (IFs) were measured by ELISA and an automatic biochemical analyzer. Besides, levels of IL-6/signal transducer and activator of transcription 3 (STAT3) pathway-related genes in rat kidney tissue were detected by qRT-PCR and western blot. the experimental results showed that IL-1β, IL-8, TNF-α and RF levels were the highest in the model group and the lowest in the control group, with those of the intervention group in between (P<0.05). Besides, the IL-6/STAT3 axis was markedly activated in the model group but inhibited in the intervention group (P<0.05). Subsequently, activated IL-6/STAT3 signal promoted IFs (IL-1β, IL-8 and TNF-α) and RF (BUN, Scr, β2-MG and UA), but this effect was offset after CX treatment (P<0.05). In conclusion, CX extract could improve RF and inhibit IRs of APN rats infected with E. coli by inhibiting the IL-6/STAT3 axis, which may be a new choice for APN treatment in the future.

Topics: Animals; Escherichia coli; Interleukin-6; Interleukin-8; Kidney; Levisticum; Plant Extracts; Pyelonephritis; Rats; Rats, Sprague-Dawley; Rhizome; STAT3 Transcription Factor; Tumor Necrosis Factor-alpha

To identify predictors of perioperative complications in children with obstructive uropathy.. 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).. 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.. Cytokines are indicators of latent inflammation in children with OU and may be predictors of perioperative complications.

Topics: Child; Cytokines; Humans; Hydronephrosis; Inflammation; Interleukin-10; Interleukin-8; Perioperative Care; Pyelonephritis; Russia; Urinary Bladder Neck Obstruction

Urinary tract infection (UTI) is a common bacterial infection among infants and children. Predicting which children with upper UTI will develop long-term sequelae remains difficult. We aimed at evaluating the predictive value of urine concentrations of interleukin-6 (UIL-6) and interleukin-8 (UIL-8) in subsequent renal scarring. In the current observational prospective study, urine samples for UIL-6 and UIL-8 were obtained from two groups: 31 children with first episode of febrile UTI and 22 febrile children of other origin. UIL-6 and UIL-8 were increased in children with febrile UTI, compared to children with fever of other origin [median and range (picograms per milliliter): (1) UIL-6, 74.46 (0-168) vs. 10.51 (0-47.50), respectively, p = 0.0001; (2) UIL-8, 2,660.38 (0-13,801) vs. 0, respectively, p = 0.0001]. Renal scarring was found in 5/31 (16 %) children with acute pyelonephritis. Initial median UIL-8 values were significantly higher in children with later renal scarring than in those without renal scarring [median and range (picograms per milliliter): 6,163 (2,021-13,801) vs. 1,490.5 (0-5,737), respectively, p = 0.018]. In conclusion, UIL-8 might serve as a predictive biomarker for renal scarring after an acute episode of pyelonephritis. Since UIL-8 emerges as a renal-specific diagnostic and prognostic marker, it may be suitable as a selective screening tool for children with febrile UTI.

Topics: Acute Disease; Biomarkers; Case-Control Studies; Child; Child, Preschool; Cicatrix; Cross-Sectional Studies; Female; Fever; Humans; Infant; Infant, Newborn; Interleukin-6; Interleukin-8; Male; Predictive Value of Tests; Prognosis; Prospective Studies; Pyelonephritis

Acute pyelonephritis (APN) is the most severe form of urinary tract infection, the etiopathogenesis of which is still not well understood. Previous studies demonstrated that chemotaxis of neutrophils into the tissue and across the infected epithelial layer is a key step in rapid bacterial clearance. Variations within genes encoding the major chemokine interleukin-8 and its receptors CXCR1 and CXCR2 are therefore attractive candidates for participation in genetic predisposition to APN. The aim of our study was to evaluate the association of single nucleotide polymorphisms (SNPs) -251 T/A, +781 C/T, +1633 C/T and +2767 A/T in the IL-8 gene, +2608 G/C in the CXCR1 gene and +1208 C/T in the CXCR2 gene with susceptibility to APN in the Slovak population. PCR-SSP and PCR-RFLP were used to genotype SNPs in 147 children with APN (62 with recurrent and 85 with episodic form) and 215 healthy individuals. Statistical analysis revealed significantly increased frequency of CXCR1 +2608 C allele (P = 0.0238, OR = 2.452, 95% CI = 1.147-5.243) and GC genotype (P = 0.0201, OR = 2.627, 95% CI = 1.188-5.810) and lower frequency of CXCR2 +1208 T allele (P = 0.0408, OR = 0.645, 95% CI = 0.429-0.972) and TT+TC genotypes (P = 0.0497, OR = 0.5273, 95% CI = 0.288-0.964) in patients with recurrent APN compared with healthy controls. Furthermore, the A allele of IL-8 -251 T/A SNP was also significantly overrepresented in patients with recurrent APN when compared with those with only single episode of APN (P = 0.0439, OR = 1.627, 95% CI = 1.019-2.599). Our results indicate that the minor CXCR1 +2608 C allele is associated with significantly increased susceptibility to APN in childhood, while the CXCR2 +1208 T allele confers protection from recurrent APN. Moreover, allele A of the IL-8 -251 T/A may also increase the risk of developing recurrent attacks after the first-time APN.

Topics: Acute Disease; Adolescent; Alleles; Case-Control Studies; Child; Child, Preschool; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Testing; Genome, Human; Genotyping Techniques; Humans; Infant; Interleukin-8; Male; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Pyelonephritis; Receptors, G-Protein-Coupled; Receptors, Interleukin-8B; Recurrence; Risk Factors; Slovakia; Young Adult

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

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

Patient susceptibility to bacterial urinary tract infections, which is determined by complex pathogen-host interactions, varies between individuals due to genetic variation. The neutrophil-dependent innate immune system is an important part of keeping the urinary tract sterile. This study was performed to explore single nucleotide polymorphisms (SNPs) in genes associated with neutrophil-dependent immunity in pediatric patients with severe parenchymal infections.. The subjects included patients who fulfilled the diagnostic criteria of acute pyelonephritis (APN) and acute lobar nephronia (ALN) without underlying disease or structural anomalies (excluding vesicoureteral reflux). Genotyping of the genes encoding toll-like receptor 4 (TLR-4), interleukin-8 (IL-8), and IL-8 receptors CXCR1 and CXCR2 was performed by matrix-assisted laser desorption/ionization time-of-flight-based mini-sequencing analysis.. A total of 17 SNPs, including missense SNPs and those located in promoter regions, were initially selected for genotyping. Only 4 SNPs with a heterozygosity rate >0.01 were evaluated further. The observed genotype frequencies satisfied Hardy-Weinberg equilibrium. Statistical analysis revealed that only IL-8 (rs4073, -251A>T) showed significant differences in genotype and allele frequency between the control and APN or ALN cases. Following the elimination of vesicoureteral reflux, which is a significant risk factor for severe parenchymal infection, a single SNP in IL-8 (rs4073) was found to be associated with clinically severe ALN.. The AA genotype and A allele of the IL-8 SNP is related to patient susceptibility to parenchymal infection and is correlated with the severity of infection in pediatric APN and ALN patients, probably due to the upregulation of IL-8 expression.

Topics: Adolescent; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Humans; Infant; Interleukin-8; Male; Molecular Sequence Data; Polymorphism, Single Nucleotide; Pyelonephritis; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Sequence Analysis, DNA; Toll-Like Receptor 4

Interleukin (IL)-8 acts as a potent neutrophils chemoattractant responsible for the migration of neutrophils into the infected renal tissue to protect against invading pathogens. The aim of this study was to assess the role of IL-8 on acute-phase pyelonephritis and later renal scarring in children.. A total of 124 children with a first-time febrile urinary tract infection (UTI) were studied. The diagnosis of acute pyelonephritis was confirmed by Tc-dimercaptosuccinic acid (DMSA) renal scan. Serum and urine samples were obtained from 124 children with UTI and 20 healthy children for IL-8 measurement.. The 124 children were divided into acute pyelonephritis (n = 70) and lower UTI (n = 54) groups according to the results of DMSA scans. The initial serum and urine IL-8 values of children with acute pyelonephritis were significantly higher when compared with lower UTI and healthy controls (all P < 0.001). Renal scarring was seen in 26 (38.8%) of these 67 children with acute pyelonephritis at follow-up DMSA scans. Both the initial serum and urine IL-8 concentrations were significantly higher in children with renal scarring than in those without (both P < 0.001). The mean age of children with renal scarring was also significantly lower than those without scarring (P = 0.004). Multivariate analysis showed that the highest initial IL-8 values, age <20 months and reflux grades > or =III all were independent predictors of renal scarring.. Those children younger than 2 years of age with the highest IL-8 concentrations during the acute phase of pyelonephritis as well as children with reflux grades of III or greater are at a high-risk for developing renal scarring in the future.

Topics: Child, Preschool; Cicatrix; Female; Humans; Infant; Interleukin-8; Kidney; Male; Pyelonephritis; Serum; Urine

Cytokines play a major role in renal scar formation following febrile urinary tract infection (UTI). We investigated the role of dexamethasone combined with antibiotics in diminishing urinary interleukin-6 (UIL-6) and UIL-8 concentrations during the acute phase of pyelonephritis compared with standard antibiotic therapy. UIL-6 and UIL-8 concentrations were determined by enzyme immunoassay in 34 children with pyelonephritis who were treated with ceftriaxone plus dexamethasone (case group) and in 20 patients with the same diagnosis treated with ceftriaxone alone (control group). Urine samples were obtained at the time of presentation prior to drug administration and at follow-up 72 h after initiation of medication. Creatinine concentrations were also determined, and cytokine/creatinine ratios were calculated to standardize samples. Differences between cytokine/creatinine ratios in initial and follow-up urine samples were significant in the case group (P < 0.001) but not for controls. In addition, combined antibiotic and dexamethasone significantly decreased UIL-6 and UIL-8 concentrations compared with antibiotic alone (P < 0.05). We conclude that dexamethasone combined with antibiotics significantly decreases UIL-6 and UIL-8 levels in patients with acute pyelonephritis. This suggests that the clinical use of corticosteroids may prevent scar formation following febrile UTI.

Topics: Acute Disease; Ceftriaxone; Child; Child, Preschool; Cicatrix; Creatinine; Cytokines; Dexamethasone; Female; Humans; Infant; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Pyelonephritis; Urinary Tract Infections; Vesico-Ureteral Reflux

Based on the implication of soluble triggering receptor expressed on myeloid cells (sTREM-1) in the septic cascade, it was investigated whether it participates or not in posttraumatic systemic inflammatory response syndrome (SIRS).. Blood was sampled on days 1, 4, 7, and 15 from 69 patients with SIRS after multiple injuries and upon presentation of a septic complication. Concentrations of sTREM-1, tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-6, IL-8, and interferon-gamma were determined by an enzyme immunoassay. Samples drawn on day 1 from 10 trauma patients without SIRS served as controls.. In 26 patients with SIRS without septic complication, sTREM-1, TNFalpha, and IL-8 remained stable over follow-up; IL-6 decreased and interferon-gamma increased on days 4 and 7 compared with day 1. TNFalpha was the only variable being higher upon advent of septic shock compared with patients without SIRS and upon presentation of SIRS, sepsis, and severe sepsis (p of comparisons with all subgroups <0.0001). Mortality of patients with sTREM-1 greater than 180 pg/mL was 5.3% compared with 28.0% of those with sTREM-1 lower than 180 pg/mL (p 0.035). sTREM-1 higher than 40 pg/mL had sensitivity 56.5% and specificity 91.7% for the differential diagnosis between SIRS and sepsis after multiple injuries.. This is the first study providing evidence about the participation of sTREM-1 in posttraumatic SIRS. Its levels are increased and remain constant over time in patients who did not develop any complications whereas it seems to behave as an anti-inflammatory mediator.

Topics: Adult; Aged; Bacteremia; Cross Infection; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Gram-Negative Bacterial Infections; Humans; Injury Severity Score; Interferon-gamma; Interleukin-6; Interleukin-8; Male; Membrane Glycoproteins; Middle Aged; Multiple Organ Failure; Multiple Trauma; Pneumonia, Bacterial; Predictive Value of Tests; Prognosis; Prospective Studies; Pyelonephritis; Receptors, Immunologic; Shock, Septic; Systemic Inflammatory Response Syndrome; Time Factors; Triggering Receptor Expressed on Myeloid Cells-1; Tumor Necrosis Factor-alpha

The aim of this study was to assess urinary interleukin-8 (IL-8) levels in pyelonephritis and its relation with the clinical course of the infection and of inflammatory changes detected by renal scintigraphy.. In this quasi-experimental before-after study, we evaluated 91 children aged 1 to 144 months (mean 34.4 +/- 35.2 months) with pyelonephritis. Inflammatory markers including erythrocyte sedimentation rate, C-reactive protein, leukocyte count, and urinary IL-8, together with the results of ultrasonography, voiding cystourethrography, and dimercaptosuccinic acid renal scintigraphy were evaluated in these children. The ratios of urinary IL-8 to creatinine (IL-8/C) before and after the treatment were compared with each other.. Urinary IL-8/C levels were significantly higher after the empirical treatment in comparison with those before the treatment (0.19 +/- 0.21 versus 0.51 +/- 0.53, P < .001). No correlation was found between the urinary IL-8 levels and leukocyturia, urine culture results, other inflammatory markers, or findings of imaging examinations.. We found high urinary IL-8 levels in children with pyelonephritis. We also documented its increasing after the treatment. We conclude that evaluation of urinary IL-8 can be a noninvasive test for diagnosis of upper urinary tract infection and its response to treatment.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Biomarkers; Child; Child, Preschool; Creatinine; Female; Humans; Infant; Interleukin-8; Male; Prospective Studies; Pyelonephritis; Pyuria

Based on the controversial findings of clinical studies regarding the influence of multidrug resistance on mortality, 10 susceptible and 10 multidrug-resistant (MDR) and extended-spectrum beta-lactamase-producing isolates of Escherichia coli were applied to stimulate monocytes isolated from healthy donors. Immune mediators were estimated in supernatants. Four susceptible isolates (Group A) and four MDR isolates (Group B) were used to initiate acute pyelonephritis in 48 rabbits following inoculation of the pathogen into the right renal pelvis. Survival was recorded and blood monocytes were isolated and incubated to estimate the ex vivo release of tumour necrosis factor-alpha (TNFalpha). Release of TNFalpha, interleukin (IL)-6 and IL-8 was higher after 2 h and 4 h of stimulation by MDR isolates compared with susceptible isolates. The opposite occurred for the release of IL-12. Death occurred in 22 rabbits in Group A (91.7%) compared with 12 in Group B (50.0%) (P=0.003). Monocytes isolated at 24 h from Group A rabbits released significantly higher TNFalpha than monocytes from Group B. Tissue bacterial load after animal death was significantly higher in the kidneys of Group A rabbits. It is concluded that susceptible and MDR E. coli stimulate monocytes resulting in a different pattern of release of pro-inflammatory cytokines, which is accompanied by prolonged survival following experimental sepsis by MDR isolates.

Topics: Animals; beta-Lactamases; Cells, Cultured; Colony Count, Microbial; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Interleukin-12; Interleukin-6; Interleukin-8; Kidney; Male; Monocytes; Pyelonephritis; Rabbits; Survival Analysis; Tumor Necrosis Factor-alpha

We performed a case-control study in children diagnosed by the first episode of upper urinary tract infection with or without vesicoureteral reflux to evaluate the association of functional polymorphism of interleukin-8 (-251A>T and +2767A>G), and its receptor CXCR1 (+2607G>C).. Genomic DNA was obtained from 265 children with a clinical and laboratory diagnosis of urinary tract infection who were recruited in northeast Italy. The children were subdivided as 173 who were dimercapto-succinic acid scan positive with positive static renal scintigraphy in acute conditions, consistent with the diagnosis of acute pyelonephritis, and 92 who were dimercapto-succinic acid scan negative. Genetic analysis for the same polymorphisms was also extended to a control population of 106 umbilical cord DNA samples.. Statistical analysis of genotype data showed that 1) the tested populations were in Hardy-Weinberg equilibrium, 2) there were significant differences between the dimercapto-succinic acid scan positive and negative groups (p=0.049), and the dimercapto-succinic acid scan positive group vs controls (p=0.032) in terms of interleukin-8 -251A>T polymorphism frequency, 3) there was also a significant difference in the distribution of IL-8 -251A>T and +2767A>G polymorphisms between dimercapto-succinic acid scan positive and negative children in the subgroup without vesicoureteral reflux (p=0.03 and 0.02, respectively) and 4) no significant differences were found in the frequency of the distribution of CXCR1 +2607G>C polymorphism in all groups.. These data suggest that the gene for the proinflammatory chemokine interleukin-8 is involved in susceptibility to acute pyelonephritis during upper urinary tract infection in children with or without vesicoureteral reflux.

Topics: Acute Disease; Case-Control Studies; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Humans; Infant; Infant, Newborn; Interleukin-8; Male; Polymorphism, Genetic; Pyelonephritis; Receptors, Interleukin-8A; Urinary Tract Infections; Vesico-Ureteral Reflux

Urinary tract infection (UTI) is a common clinical disorder in younger infants and children and may result in permanent renal damage. The inflammatory cytokines interleukin (IL)-6 and IL-8 play an important role in response to bacterial infection. This prospective study investigated the association between serum and urine IL-6 and IL-8 levels and acute pyelonephritis confirmed by (99m)Tc-dimercaptosuccinic acid (DMSA) scan. A total of 78 children aged 1-121 months with a diagnosis of first-time febrile UTI were included. The following inflammatory markers were assessed: fever; white blood cells count (WBC); C-reactive protein (CRP); and serum and urine IL-6 and IL-8. The patients were divided into the acute pyelonephritis group (n=42) and the lower UTI group (n=36) according to the results of DMSA scan. Fever, WBC and CRP levels were significantly higher in children with acute pyelonephritis than in those with lower UTI (all p <0.001). Significantly, higher initial serum and urine IL-6 and IL-8 levels were found in children with acute pyelonephritis than in those with lower UTI (all p <0.001). Serum and urine IL-6 in children with acute pyelonephritis were positively correlated with fever, CRP and leucocyturia. These results indicate that both serum and urine IL-6 and IL-8 levels, particularly IL-6, are useful diagnostic tools for early recognition of acute pyelonephritis in febrile children.

Topics: Child; Child, Preschool; Female; Humans; Infant; Interleukin-6; Interleukin-8; Male; Pyelonephritis; Vesico-Ureteral Reflux

Uropathogenic bacteria stimulate epithelial cells of interstitial tissue and macrophages to secrete proinflammatory cytokines: interleukin I (IL-1beta), interleukin 6 (IL-6) and interleukin 8 (IL-8). The aim of the study was to check: 1) if the concentration of proinflammatory cytokines (IL-1beta, IL-6, IL-8) differs in dependence on region and clinical picture of urinary tract infection, 2) what is the influence of antibacterial treatment on their concentration.. We examined 67 children, aged 1-15 years, who were divided into 3 groups: 27 children with acute pyelonephritis (AP), caused by E. coli (group I), in whom the examination was carried out twice: A - before treatment, B - after 14 days of antibacterial treatment, 10 children with chronic urinary tract infection (UTI) associated with neurogenic bladder (group II) and 30 healthy children (group K).. Urinary concentration of examined cytokines was assessed using ELISA immunoenzymatic method and was expressed in pg/mg creatinine. Results showed that in group I before treatment the urinary concentration of examined cytokines was increased (p<0.05). After antibacterial treatment concentration of IL-1beta was normal and concentration of IL-6 and IL-8 decreased but was still higher than in control group (p<0.05). In group II before treatment the increase in concentration of IL-1beta and IL-8 was not so high (p<0.05) and the urinary concentration of IL-6 was normal (p>0.05). In examination A in children from group I and II a positive correlation between examined cytokines and C reactive protein was shown. We have also found a positive correlation between urinary concentration of IL-1beta a IL-8.. 1. Urinary concentration of examined proinflammatory cytokines is different in children with AP and UTI associated with neurogenic bladder and correlates with concentration of C-reactive protein. 2. In most of children with AP after 14-days of antibacterial treatment the urinary concentration of proinflammatory cytokines has been increased.

Topics: Adolescent; Analysis of Variance; C-Reactive Protein; Case-Control Studies; Child; Child, Preschool; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant; Interleukin-1; Interleukin-6; Interleukin-8; Male; Poland; Pyelonephritis; Risk Factors; Statistics, Nonparametric; Urinary Bladder, Neurogenic; Urinary Tract Infections

Topics: Adolescent; Child; Data Interpretation, Statistical; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Interleukins; Male; Pyelonephritis; Statistics, Nonparametric; Vesico-Ureteral Reflux

The urine concentration of IL-6, IL-8 and nitric oxide (NO) were determined in the patients with pyelonephritis and hydronephrosis. Correlations between urine levels of IL-6 and IL-8 and amount of nitric oxide in the hydronephrosis patients were not found. However, in the patients with both acute and chronic pyelonephritis the coefficient of correlation was high, r((IL-6/NO)) = 0,94 and r((IL-8/NO)) = 0,86 for acute and r((IL-6/NO)) = 0,72 and r((IL-8/NO)) = 0,40 for chronic forms, respectively. These data suggest that secretion of NO during hydronephrosis has a compensatory character and acted on renal microvascular tone, whereas during pyelonephritis NO produced inflammatory mediators by recruiting leukocytes and has pathogenic character.

Topics: Adult; Female; Humans; Hydronephrosis; Interleukin-6; Interleukin-8; Male; Middle Aged; Nitric Oxide; Pyelonephritis

The evolution and the relationship between inflammatory and renal-injury markers in women with acute uncomplicated pyelonephritis under antimicrobial therapy were investigated in a prospective study. Markers were measured before and 6 and 24 h after the intravenous administration of 1 g of ceftriaxone. Before treatment, the median levels of all markers except the serum creatinine levels were high. Twenty-four hours after the onset of antibiotic treatment, the C-reactive protein (CRP) level continued to be high, while the serum interleukin-6 (IL-6) levels and the urine IL-6, IL-8, albumin, and immunoglobulin G (IgG) levels decreased significantly. In contrast, serum creatinine and tumor necrosis factor alpha levels and urine N-acetyl-beta-glucosaminidase, alpha1-microglobulin, and beta2-microglobulin levels did not change over time. There was a significant correlation between IL-6 and IL-8 levels and urine albumin and IgG levels (urine albumin and IgG levels are glomerular and urinary tract-injury markers) as well as between serum CRP levels and the levels of the tubular-injury markers. In women with acute pyelonephritis, appropriate antibiotic treatment rapidly decreases serum IL-6 levels and urine IL-6 and IL-8 levels, which correlate well with urine albumin and IgG levels.

Topics: Acute Disease; Adult; Aged; Anti-Bacterial Agents; Biomarkers; C-Reactive Protein; Ceftriaxone; Escherichia coli Infections; Female; Humans; Immunoglobulin G; Inflammation Mediators; Interleukin-6; Interleukin-8; Kidney; Middle Aged; Prospective Studies; Pyelonephritis

Neutrophil migration to infected mucosal sites involves a series of complex interactions with molecules in the lamina propria and at the epithelial barrier. Much attention has focussed on the vascular compartment and endothelial cells, but less is known about the molecular determinants of neutrophil behavior in the periphery. We have studied urinary tract infections (UTIs) to determine the events that initiate neutrophil recruitment and interactions of the recruited neutrophils with the mucosal barrier. Bacteria activate a chemokine response in uroepithelial cells, and the chemokine repertoire depends on the bacterial virulence factors and on the specific signaling pathways that they activate. In addition, epithelial chemokine receptor expression is enhanced. Interleukin (IL)-8 and CXCR1 direct neutrophil migration across the epithelial barrier into the lumen. Indeed, mIL-8Rh knockout mice showed impaired transepithelial neutrophil migration, with tissue accumulation of neutrophils, and these mice developed renal scarring. They had a defective antibacterial defense and developed acute pyelonephritis with bacteremia. Low CXCR1 expression was also detected in children with acute pyelonephritis. These results demonstrate that chemokines and chemokine receptors are essential to orchestrate a functional antimicrobial defense of the urinary tract mucosa. Mutational inactivation of the IL-8R caused both acute disease and chronic tissue damage.

Topics: Animals; Bacterial Adhesion; Bacteriuria; Chemotaxis, Leukocyte; Child; Disaccharides; Drosophila Proteins; Escherichia coli; Escherichia coli Infections; Fimbriae, Bacterial; Genetic Predisposition to Disease; Glycosphingolipids; Humans; Immunity, Innate; Interleukin-8; Macrophages; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Knockout; Mucous Membrane; Neutrophils; Pyelonephritis; Receptors, Cell Surface; Receptors, Chemokine; Receptors, Interleukin-8A; Recurrence; Toll-Like Receptors; Urinary Tract Infections; Urothelium; Virulence

Urinary tract infections are common in infants and children. Pyelonephritis may result in serious complications, such as renal scarring, hypertension, and renal failure. Identification of the timing of release of inflammatory cytokines in relation to pyelonephritis and its treatment is essential for designing interventions that would minimize tissue damage. To this end, we measured urinary cytokine concentrations of interleukin-1 beta (IL-1 beta), IL-6, and IL-8 in infants and children with pyelonephritis and in healthy children. Children that presented to our institution with presumed urinary tract infection were given the diagnosis of pyelonephritis if they had a positive urine culture, pyuria, and one or more of the following indicators of systemic involvement: fever, elevated peripheral white blood cell count, or elevated C-reactive protein. Urine samples were obtained at the time of presentation prior to the administration of antibiotics, immediately after completion of the first dose of antibiotics, and at follow up 12 to 24 h after presentation. IL-1 beta, IL-6, and IL-8 concentrations were measured by enzyme-linked immunosorbent assay. Creatinine concentrations were also determined, and cytokine/creatinine ratios were calculated to standardize samples. Differences between pre-antibiotic and follow-up cytokine/creatinine ratios were significant for IL-1 beta, IL-6, and IL-8 (P < 0.01). Differences between pre-antibiotic and control cytokine/creatinine ratios were also significant for IL-1 beta, IL-6, and IL-8 (P < 0.01). Our study revealed that the urinary tract cytokine response to infection is intense but dissipates shortly after the initiation of antibiotic treatment. This suggests that renal damage due to inflammation begins early in infection, underscoring the need for rapid diagnosis and intervention.

Topics: Anti-Bacterial Agents; Child; Child, Preschool; Cytokines; Female; Humans; Infant; Infant, Newborn; Interleukin-1; Interleukin-6; Interleukin-8; Male; Pyelonephritis

In upper urinary tract infections, tubular epithelial cells (TEC) may play a pivotal role in the initiation of the renal inflammatory response. They exert crucial immunological functions such as processing and presentation of foreign antigen, secretion of proinflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor alpha) and chemokines (IL-8, MCP-1, ENA-78, and RANTES). Since monolayer cultures are a limited model for polarized tubular epithelial cells, we studied the side-dependent IL-8 secretion of TEC by using cell culture inserts as a basement membrane imitation. Primary cultures of proximal TEC were stimulated with differently fimbriated mutants of Escherichia coli, E. coli LPS, S-fimbria isolates, and IL-1alpha. IL-8 protein was measured by enzyme-linked immunosorbent assay, and IL-8-like biological activity was tested by measuring elastase release from polymorphonuclear cells in supernatants of the upper and lower compartments. IL-8 mRNA was compared by competitive PCR. IL-8 secretion by TEC into the basolateral environment was significantly higher than secretion into the apical compartment, representing the tubular lumen. However, stimulation of IL-8 secretion by TEC was restricted to IL-1alpha and was not inducible by E. coli mutants, S fimbriae, or lipopolysaccharide. With this in vitro model of polarized TEC, we show that luminal contact of TEC with uropathogenic E. coli does not result in enhanced IL-8 secretion. The basolaterally directed production of the neutrophil chemotactic factor IL-8 by TEC after stimulation with IL-1alpha might play an important role in the initiation of inflammatory cell influx into the renal parenchyma.

Topics: Base Sequence; Cell Polarity; Cells, Cultured; DNA Primers; Epithelial Cells; Escherichia coli; Escherichia coli Infections; Fimbriae, Bacterial; Gene Expression; Humans; Immunohistochemistry; Interleukin-1; Interleukin-8; Kidney Cortex; Kidney Tubules; Lipopolysaccharides; Microscopy, Electron; Mutation; Pyelonephritis; RNA, Messenger

Pyelonephritis is one of the most common febrile diseases in children. If not treated appropriately, it causes irreversible renal damage and accounts for a large proportion of end stage renal failures. Renal scarring can occur in the absence of inflammatory cells, indicating that bacteria may have a direct signalling effect on renal cells. Intracellular calcium ([Ca2+]i) oscillations can protect cells from the cytotoxic effects of prolonged increases in intracellular calcium. However, no pathophysiologically relevant protein that induces such oscillations has been identified. Here we show that infection by uropathogenic Escherichia coli induces a constant, low-frequency oscillatory [Ca2+]i response in target primary rat renal epithelial cells induced by the secreted RTX (repeats-in-toxin) toxin alpha-haemolysin. The response depends on calcium influx through L-type calcium channels as well as from internal stores gated by inositol triphosphate. Internal calcium oscillations induced by alpha-haemolysin in a renal epithelial cell line stimulated production of cytokines interleukin (IL)-6 and IL-8. Our findings indicate a novel role for alpha-haemolysin in pyelonephritis: as an inducer of an oscillating second messenger response in target cells, which fine-tunes gene expression during the inflammatory response.

Topics: Animals; Bacterial Proteins; Calcium; Calcium Channel Blockers; Calcium Channels, L-Type; Cell Line; Epithelial Cells; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Estrenes; Female; Hemolysin Proteins; Humans; Interleukin-6; Interleukin-8; Kidney; Nifedipine; Pyelonephritis; Pyrrolidinones; Rats; Rats, Sprague-Dawley

CXC chemokines are chemotactic cytokines that specifically act on neutrophils. To obtain insight into the extent of local production of CXC chemokines during acute pyelonephritis, interleukin (IL)-8, growth-related oncogene (GRO)-alpha, and epithelial cell-derived neutrophil-activating protein (ENA)-78 were measured in urine and plasma samples from patients with culture-proven urosepsis (n=33), healthy human control subjects with sterile urine (n=31), and human volunteers intravenously injected with endotoxin (n=11). Patients had profoundly elevated urine concentrations of chemokines with no (GRO-alpha and ENA-78) or little (IL-8) elevation in plasma. Endotoxin-challenged subjects demonstrated transient increases in plasma chemokine concentrations, with no (GRO-alpha) or little (IL-8 and ENA-78) elevation in urine. Urine from patients exerted chemotactic activity toward neutrophils, which was partially inhibited by neutralizing antibodies against IL-8, GRO-alpha, or ENA-78. During urosepsis, CXC chemokines are predominantly produced within the urinary tract, where they are involved in the recruitment of neutrophils to the urinary compartment.

Topics: Acute Disease; Adult; Antibodies; Chemokine CXCL5; Chemokines, CXC; Endotoxins; Growth Substances; Humans; Interleukin-8; Neutrophil Activation; Neutrophils; Pyelonephritis

To investigate bacterial growth and inflammatory mediator release in the early stage of the immune response, a unilateral acute ascending pyelonephritis was induced in rats by intrabladder inoculation of Escherichia coli. The infected left kidney showed a significant bacterial proliferation, local production of interleukin (IL)-6 and IL-8 as detected by immunocytochemistry, and extensive destruction of renal parenchyma associated with impressive leukocyte recruitment. Inducible and constitutive nitric oxide synthases (NOS) were locally expressed, and a time-dependent increase in urinary secretion of nitric oxide (NO) was seen that could be blocked by NG-monomethyl-L-arginine. However, there was a discrepancy between the NO profile in the kidney and urine. The results demonstrate that in the early stage of acute pyelonephritis kidney tubules participate actively in the local host response by producing important inflammatory mediators and that urinary NO levels are not suitable for predicting renal NOS activity.

Topics: Acute Disease; Animals; Colony Count, Microbial; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Female; Immunohistochemistry; Inflammation Mediators; Interleukin-6; Interleukin-8; Kidney; Macrophages; Monocytes; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Pyelonephritis; Rats; Rats, Sprague-Dawley

Interleukin (IL)-6 and -8 are important inflammatory cytokines in bacterial infections. Their serum and urine concentrations were measured in 27 neonates with urinary tract infection (UTI) at onset and the second week of therapy, as well as in 23 control neonates. Escherichia coli was isolated in 89% of cases. 99mTc-dimercaptosuccinic acid (99mTc-DMSA) scans were performed between the 10th and 90th days after UTI and showed pyelonephritic changes in 15 neonates (56%). Increased IL-6 and IL-8 concentrations were found in urine but not in serum within the first 24 h after presumptive diagnosis of UTI (P=.036 and.010, respectively), suggesting that the neonatal urinary tract can respond to uropathogens by producing inflammatory cytokines. Urine concentrations of IL-6 correlated with findings of renal changes in 99mTc-DMSA scans (P=.012) and thus may serve as a marker of renal parenchymal outcome. All neonates exhibited undetectable urine cytokine levels during the second week of therapy.

Topics: Female; Follow-Up Studies; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Kidney; Male; Pyelonephritis; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Dimercaptosuccinic Acid; Urinary Tract Infections

The study of interleukine-8 (IL-8) and defensines contribution to pathogenesis of chronic glomerulonephritis (CGN) and pyelonephritis (PN).. 122 patients were assigned to three groups: 42 CGN patients with isolated urinary syndrome (group 1); 60 patients with chronic pyelonephritis (CP) with normal nitrogen-excretory function (group 2); 20 patients with CGN and chronic renal failure (CRF) (group 3). 24 healthy volunteers served control. IL-8 and defensines were measured in urine and plasm of all the patients and controls using enzyme immunoassay.. IL-8 in urine and plasm of controls was not found, in plasm of patients was found in 45%, the differences between the groups being insignificant. The highest IL-8 urine concentration was found in group 2. It was significantly higher than in group 1 and 3 (p < 0.001). Mean IL-8 urine concentration in patients with secondary pyelonephritis was significantly higher than in those with primary pyelonephritis (p < 0.05). In primary pyelonephritis, urinary IL-8 was higher than in patients of groups 1 and 3 (p < 0.001). Mean urinary IL-8 was significantly higher in patients of group 3 than 1 (p < 0.005). IL-8 urinary concentrations of group 3 patients tended to an increase with growing severity of renal failure. Plasm defensines were present in 46.5% of patients without marked differences between the groups. Urine defensines were the highest in group 2 being significantly higher than in group 1, 3 and controls (p < 0.001). Urine defensines in group 1 were slightly higher than in controls and significantly reduced vs group 3 (p < 0.005). Urine defensines concentrations rose with CGN stage. A strong positive correlation was established between IL-8 and defensines in urine (r = 0.62), leukocyturia and IL-8 in urine (r = 0.52). A weak positive correlation (r = 0.38) existed between proteinuria and urine IL-8 only in group 3 patients. A week later concentrations of IL-8 and defensines were low in group 2. In group 1 they rose, fell or remained unchanged.. IL-8 and defensines may be of the same pathogenetic importance both in infectious and non-infectious inflammation in the kidneys. Cytotoxic action of defensines can be related to location of the inflammation in the kidney. IL-8 urine tests can be used in monitoring of inflammation activity and diagnosis of latent glomerulonephritis and pyelonephritis.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood Proteins; Chronic Disease; Defensins; Female; Glomerulonephritis; Humans; Immunoenzyme Techniques; Interleukin-8; Male; Middle Aged; Proteins; Pyelonephritis; Severity of Illness Index

Interleukin-8 (IL-8) plays a crucial role in the recruitment and activation of polymorphonucleated leukocytes (PMN) in the site of inflammation. Defensins are specific cationic proteins from azurophil PMN granules which exert antimicrobial, cytotoxic and proinflammatory activities.. Urine and plasma levels of IL-8 and defensins were studied using specific enzyme-linked immunosorbent assays. IL-8 was determined in 107 patients, including 45 with chronic glomerulonephritis (GN) and 62 with chronic pyelonephritis (PN). Urine and plasma levels of defensins were studied simultaneously in 29 patients with GN and 29 with PN. None of the patients examined showed any evidence of renal insufficiency. A group of 24 healthy volunteers was used as a control.. Urinary IL-8 was significantly increased in all groups of patients comparing with healthy control (< 30 pg/ml). The level of IL-8 in the urine of patients with PN (477 +/- 114 pg/ml, mean +/- SEM) was significantly (P < 0.001) higher than in patients with GN (53 +/- 7 pg/ml). The concentration of defensins in urine of patients with GN was slightly increased in comparison with the normal level (21 +/- 3.5 ng/ml versus 15.7 +/- 2.8 ng/ml). Urinary defensins were significantly elevated in patients with PN (134 +/- 118 ng/ml, P < 0.001), and were significantly higher than in the GN group (P < 0.001). A close correlation was observed between IL-8 and defensin concentrations in urine (r = 0.62), and between the urinary leukocyte count and IL-8 level (r = 0.72). The highest levels of IL-8 were observed in patients with PN, associated with nephrolithiasis (14 patients, 822 +/- 219 pg/ml versus 367 +/- 72 pg/ml in patients with PN alone, P < 0.05). IL-8 and defensin levels increased in older patients with PN, but not in older patients with GN.. The levels of IL-8 and defensins in urine were 6-10-fold higher in patients with PN than in patients with GN. Thus, there is a significant difference in IL-8 production between septic and aseptic chronic inflammatory processes in kidney. It is possible to speculate that the timing and progression of kidney inflammation is mediated by an IL-8 dependent mechanism at least in the case of PN.

Topics: Adolescent; Adult; Aged; Blood Proteins; Defensins; Female; Glomerulonephritis; Humans; Immunoenzyme Techniques; Interleukin-8; Male; Middle Aged; Pyelonephritis; Reference Values

The relationship between urine interleukin-6 (IL-6) and interleukin-8 (IL-8)/creatinine quotients and 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy, performed within 10 days of acute first-time pyelonephritis and after 1 year, was studied in 41 children. The urine IL-6 and IL-8/creatinine quotients were also related to the urine N-acetyl-beta-D-glucosaminidase (NAG) and albumin/creatinine quotients. Presence of DMSA uptake defects, reflecting local inflammation, in children in the acute phase of pyelonephritis, were associated with elevated urine IL-6/creatinine quotients (median 27 pg/mumol); in children without DMSA changes there was no increase in quotients (median non-detectable) (P < 0.05). Persistent DMSA changes at the 1-year follow-up, probably reflecting renal scarring, were only seen in children with increased urine IL-6/creatinine quotients in the acute phase (P < 0.01). No correlation was found between urine IL-8 and DMSA uptake defects. Vesicoureteral reflux (VUR) at 6-8 weeks did not correlate with the urine cytokine levels in the acute phase. The urine excretion of NAG and albumin, reflecting renal dysfunction, was associated with values of both urine IL-6 and IL-8/creatinine quotients, but not with DMSA defects or VUR. Thus, the initial urine IL-6/creatinine quotients might be used as an indicator of risk for persistent renal damage in acute pyelonephritis.

Topics: Acetylglucosaminidase; Acute Disease; Albuminuria; Child; Child, Preschool; Creatinine; Follow-Up Studies; Humans; Infant; Infant, Newborn; Interleukin-6; Interleukin-8; Kidney; Organotechnetium Compounds; Pyelonephritis; Radionuclide Imaging; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid; Vesico-Ureteral Reflux

Urine and serum concentrations of interleukin (IL)-6 and IL-8 were determined in 43 women with acute pyelonephritis caused by Escherichia coli. Urine and serum samples were also collected 2 weeks after the infection and during a subsequent episode of cystitis (n = 8) or asymptomatic bacteriuria (n = 8). Concentrations of IL-6 and IL-8 were related to the expression of 5 virulence markers of E. coli and glomerular filtration rate (GFR) after pyelonephritis. Patients with acute pyelonephritis had elevated urine and serum IL-6 and IL-8 levels as compared to 37 healthy women (IL-6: p < 0.001 in both cases, and IL-8: p < 0.001 in both cases). Patients infected with E. coli producing hemolysin and/or cytotoxic necrotizing factor (CNF) had significantly higher IL-6 levels in serum during acute pyelonephritis as compared to patients infected with strains without the ability to produce these factors (p = 0.0025 and p = 0.0154, respectively). Patients who had high concentrations of IL-8 in urine during acute pyelonephritis had lower GFR at follow-up as compared to patients with lower levels of IL-8 in urine (r = -0.48, p = 0.0123). In conclusion, acute pyelonephritis is accompanied by elevated urinary and serum IL-6 and IL-8 levels. Bacteria producing hemolysin and CNF seem to induce higher concentrations of IL-6 in serum. The secretion of IL-8 from renal cells may participate in the initiation and maintenance of renal inflammation which in turn may influence renal function.

Topics: Acute Disease; Adolescent; Adult; Bacterial Toxins; C-Reactive Protein; Cytotoxins; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Fimbriae, Bacterial; Glomerular Filtration Rate; Hemolysin Proteins; Humans; Interleukin-6; Interleukin-8; Kidney; Middle Aged; Pyelonephritis; Virulence

Interleukin-6 (IL-6) and interleukin-8 (IL-8) are important mediators of the inflammatory response in serious bacterial infections. We studied the levels of these two cytokines (standardised for urinary creatinine) in the urine of infants and children during and 6 weeks after acute pyelonephritis and in non-renal febrile controls and healthy children without apparent infection. IL-6 was detected in the urine of 52% of children with pyelonephritis compared with 15% of other children (P < 0.001). The median urinary IL-6 level in acute pyelonephritis was 4 pg/mumol compared with undetectable levels in the control group (P < 0.001). IL-8 was detected in 98% of children with pyelonephritis and 42% of other children (P < 0.001). The median concentration of IL-8 was 188 pg/mumol in pyelonephritis; it was undetectable in controls (P < 0.001). IL-8 levels were higher in children less than 1 year of age (P < 0.001).

Topics: Acute Disease; Child; Child, Preschool; Female; Humans; Immunoenzyme Techniques; Infant; Interleukin-6; Interleukin-8; Male; Pyelonephritis; Recurrence