Evaluation of urinary IL-1α and IL-1β in gravid females and patients with bacterial cystitis and microscopic hematuria

Candela, Joseph; Park, Eun-Hee; Gerspach, Jill M.; Davidoff, Ramin; Stout, L. Clarke; Levy, Susan M.; Leach, Gary E.; Bellman, Gary C.; Lad, Pramod M.

doi:10.1007/s002400050043

Cited by 20 publications

(19 citation statements)

References 20 publications

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“…Increased serum levels of IL-6 and IL-8 were detected in bacteremic patients [31], [34], [35] and further work investigating the cytokine repertoire showed that febrile UTI causes an increase in GRO-α and ENA-78 in urine, and ENA-78 in serum [35]. Acute cystitis has been associated with an increase in urine IL-1α, GRO-α, IL-1β, IL-6, IL-8 and TNF-α compared to sterile samples [36], [37], [38]. Urine cytokine levels in ABU have been examined in transplant patients [39] and diabetic children with ABU [40].…”

Section: Discussionmentioning

confidence: 98%

Genetic Control of the Variable Innate Immune Response to Asymptomatic Bacteriuria

et al. 2011

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The severity of urinary tract infection (UTI) reflects the quality and magnitude of the host response. While strong local and systemic innate immune activation occurs in patients with acute pyelonephritis, the response to asymptomatic bacteriuria (ABU) is low. The immune response repertoire in ABU has not been characterized, due to the inherent problem to distinguish bacterial differences from host-determined variation. In this study, we investigated the host response to ABU and genetic variants affecting innate immune signaling and UTI susceptibility. Patients were subjected to therapeutic urinary tract inoculation with E. coli 83972 to ensure that they were exposed to the same E. coli strain. The innate immune response repertoire was characterized in urine samples, collected from each patient before and after inoculation with bacteria or PBS, if during the placebo arm of the study. Long-term E. coli 83972 ABU was established in 23 participants, who were followed for up to twelve months and the innate immune response was quantified in 233 urine samples. Neutrophil numbers increased in all but two patients and in an extended urine cytokine/chemokine analysis (31 proteins), the chemoattractants IL-8 and GRO-α, RANTES, Eotaxin-1 and MCP-1, the T cell chemoattractant and antibacterial peptide IP-10, inflammatory regulators IL-1-α and sIL-1RA and the T lymphocyte/dendritic cell product sIL-2Rα were detected and variably increased, compared to sterile samples. IL-6, which is associated with symptomatic UTI, remained low and numerous specific immune mediators were not detected. The patients were also genotyped for UTI-associated IRF3 and TLR4 promoter polymorphisms. Patients with ABU associated TLR4 polymorphisms had low neutrophil numbers, IL-6, IP-10, MCP-1 and sIL-2Rα concentrations. Patients with the ABU-associated IRF3 genotype had lower neutrophils, IL-6 and MCP-1 responses than the remaining group. The results suggest that the host-specific, low immune response to ABU mainly includes innate immune mediators and that host genetics directly influence the magnitude of this response.

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Section: Discussionmentioning

confidence: 98%

Genetic Control of the Variable Innate Immune Response to Asymptomatic Bacteriuria

et al. 2011

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“…Larger studies in future are likely to offer critical insights into the reproducible presence of cytokines in the urine of OAB patients. The bladder source of these cytokines can be confirmed by their comparative detection in plasma or renal urine collected by ureteral catheters [32]. In spite of these differences, the results from this pilot study serve as a framework for a larger, prospective, longitudinal study to investigate the causal relationship of these urinary inflammation biomarkers and symptoms/causes of OAB.…”

Section: Discussionmentioning

confidence: 87%

“…Urinary cytokines in OAB population may reflect the effect of a wide variety of treatments taken by the patients in the study. The obvious advantage of non-invasiveness with urinary proteomics is tempered by the increased variability arising due to intra-individual and inter-individual changes in urine volume, pH, and other urine constituents [31,32]. The approach of creatinine correction for urine levels of biomarkers is routinely used in urine proteomics [33][34][35] and it was considered valid for studies involving measurement of urine chemokines that are believed to be passively released into urine from urothelium during the storage phase of micturition.…”

Section: Discussionmentioning

confidence: 99%

Urine cytokines suggest an inflammatory response in the overactive bladder: a pilot study

et al. 2009

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“…Studies have shown that UPEC triggers inflammation that consists of immune mediators, including ILs (9)(10)(11)(12), although some of these responses, including, for example, IL-1a, occur in a pathogen-specific manner (13). Roles for TNF, NO (14), CXCR 2 (15), Tamm-Horsfall protein (16,17), and CD44 (18) have been shown in models of human UPEC UTI, although, in most cases, the functions of these host factors at the cellular and molecular levels remain unclear.…”

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confidence: 99%

Innate Transcriptional Networks Activated in Bladder in Response to Uropathogenic Escherichia coli Drive Diverse Biological Pathways and Rapid Synthesis of IL-10 for Defense against Bacterial Urinary Tract Infection

Duell

Carey

Tan

et al. 2012

The Journal of Immunology

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Early transcriptional activation events that occur in bladder immediately following bacterial urinary tract infection (UTI) are not well defined. In this study, we describe the whole bladder transcriptome of uropathogenic Escherichia coli (UPEC) cystitis in mice using genome-wide expression profiling to define the transcriptome of innate immune activation stemming from UPEC colonization of the bladder. Bladder RNA from female C57BL/6 mice, analyzed using 1.0 ST-Affymetrix microarrays, revealed extensive activation of diverse sets of innate immune response genes, including those that encode multiple IL-family members, receptors, metabolic regulators, MAPK activators, and lymphocyte signaling molecules. These were among 1564 genes differentially regulated at 2 h postinfection, highlighting a rapid and broad innate immune response to bladder colonization. Integrative systems-level analyses using InnateDB (http://www.innatedb.com) bioinformatics and ingenuity pathway analysis identified multiple distinct biological pathways in the bladder transcriptome with extensive involvement of lymphocyte signaling, cell cycle alterations, cytoskeletal, and metabolic changes. A key regulator of IL activity identified in the transcriptome was IL-10, which was analyzed functionally to reveal marked exacerbation of cystitis in IL-10–deficient mice. Studies of clinical UTI revealed significantly elevated urinary IL-10 in patients with UPEC cystitis, indicating a role for IL-10 in the innate response to human UTI. The whole bladder transcriptome presented in this work provides new insight into the diversity of innate factors that determine UTI on a genome-wide scale and will be valuable for further data mining. Identification of protective roles for other elements in the transcriptome will provide critical new insight into the complex cascade of events that underpin UTI.

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Evaluation of urinary IL-1α and IL-1β in gravid females and patients with bacterial cystitis and microscopic hematuria

Cited by 20 publications

References 20 publications

Genetic Control of the Variable Innate Immune Response to Asymptomatic Bacteriuria

Genetic Control of the Variable Innate Immune Response to Asymptomatic Bacteriuria

Urine cytokines suggest an inflammatory response in the overactive bladder: a pilot study

Innate Transcriptional Networks Activated in Bladder in Response to Uropathogenic Escherichia coli Drive Diverse Biological Pathways and Rapid Synthesis of IL-10 for Defense against Bacterial Urinary Tract Infection

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