The significance of interleukin 8 in urine.

AIMS: To assess the implications of detection of interleukin 8 (IL-8) in urine. METHODS: IL-8 was measured by immunoassay in all 305 urine samples from children aged 0-18.4 years received by our microbiology laboratory during four weeks, with a retrospective structured case note audit for all those in whom IL-8, white cells, or bacteria were detected. Patients were divided into three groups: urinary tract infection (UTI), at least one sample with >/=5 leucocytes x 10(9)/l and >/=10(5) cultured bacteria/ml; possible UTI, at least one sample with >/=5 leucocytes x 10(9)/l or >/=10(5) cultured bacteria/ml but not both; UTI unlikely, sample(s) with <5 leucocytes x 10(9)/l and <10(5) cultured bacteria/ml. Medical records were sought for all in groups 1 (14/14 found) and 2 (18/21 found) and those in group 3 (41/59 found) in whose urine any leucocytes, cultured bacteria, or IL-8 were detected. RESULTS: IL-8 was detected in 58/305 samples from 48/264 patients. IL-8 was detected in at least one urine sample from 13/14 patients with confirmed UTI (group 1); in 11/21 patients with possible UTI (group 2), of whom two were treated as UTI; and in 23/228 patients without UTI. Using a cut off of 200 pg/ml, urine IL-8 had a sensitivity of 93% and a specificity of 90% for diagnosing UTI. CONCLUSIONS: Urine IL-8 is a sensitive test for UTI, but is poorly specific as it is also present in a variety of other infectious and inflammatory disorders.

Uropathogenic Escherichia coli-induced neutrophil adhesion to urinary epithelium is strain-specific and mediated by CD11b/CD18.

Adherence of Escherichia coli to urinary tract epithelium induces neutrophil migration across the uroepithelium to combat bacterial infection. Neutrophil adherence to the apical membrane of uroepithelial cells may be an important factor for bacterial clearance. We used an in vitro model of urinary tract infection to examine the effects of uropathogenic E. coli on neutrophil adhesion to the uroepithelial cell line RT4. We found that distinct clinical isolates caused different levels of neutrophil adherence. One particular isolate caused significant neutrophil adhesion in a dose- and time-dependent manner. The neutrophil adhesion-promoting effect induced by this isolate was not caused by bacterial secreted products, suggesting that contact between intact E. coli and uroepithelial cells is required for promoting neutrophil adhesion. This adhesion was almost exclusively mediated by CD11b/CD18, suggesting that E. coli upregulates CD11b/CD18 counterligands on the uroepithelial surface. These data suggest that certain uropathogenic E. coli selectively promote adhesion of neutrophils to ligands on uroepithelial cells by a CD11b/CD18-dependent mechanism.

Potent costimulation of effector T lymphocytes by human collagen type I.

Purified, resting peripheral blood T lymphocytes were previously reported to undergo beta(1) integrin-dependent activation when cultured with anti-CD3 mAb coimmobilized with fibronectin, but not type I collagen. However, the extravascular T cells that encounter immobilized extracellular matrix proteins and are involved in disease pathogenesis have different properties from resting peripheral blood cells. In this study, we confirm that resting CD4(+) and CD8(+) T cells from peripheral blood are costimulated by immobilized fibronectin, but not type I collagen. In contrast, Ag- or mitogen-stimulated CD4(+) and CD8(+) T cell lines, used as models of the effector cells involved in disease, are more potently costimulated by type I collagen than fibronectin. The collagen-induced effects are similar in assays with serum-free medium and in more physiological assays in which anti-CD3 mAb is replaced by a threshold concentration of Ag and irradiated autologous PBMC as APC. The responses are beta(1) integrin dependent and mediated largely by very late Ag (VLA) 1 and 2, as shown by their up-regulation on the T cell lines as compared with freshly purified resting PBL, and by the effects of blocking mAb. Reversed phase HPLC located the major costimulatory sequence(s) in the alpha1 chain of type I collagen, the structure of which was confirmed by amino acid sequencing. The results demonstrate the potential importance of type I collagen, an abundant extracellular matrix protein, in enhancing the activation of extravascular effector T cells in inflammatory disease, and point to a new immunotherapeutic target.

IL-8 and neutrophil elastase levels in the respiratory tract of infants with RSV bronchiolitis.

The aim of this study was to determine whether interleukin (IL)-8 is released within the upper respiratory tract of infants during respiratory syncytial virus (RSV) bronchiolitis and whether the large number of polymorphonuclear neutrophils (PMNs) present in the respiratory tract of these infants are contributing to the inflammation through release of inflammatory mediators. Twenty-seven infants with acute bronchiolitis were recruited during one winter epidemic and 20 infant control subjects were recruited from a cohort participating in a community-based vaccine study. Samples of airways fluid were obtained using nasal lavage. The lavage fluid was spun to remove the cells, and the supernatant was stored at -70 degrees C. The supernatants were subsequently assayed for the presence of IL-8, total human neutrophil elastase (HNE) and neutrophil elastase activity. In the children with bronchiolitis compared with control infants, elevated levels of IL-8 (median (range) 1.53 (0-153) versus 0 (0-5.6) ng x mL(-1)) HNE (136 (32-694) versus 14 (0-516) ng x mL(-1)) and elastase activity (4 (1-220) versus 1 (0-339) mU x mL(-1)) were found. These results indicate that interleukin-8 is released in the upper respiratory tract in response to respiratory syncytial virus infection and suggest that polymorphonuclear neutrophil products are playing an important role in the inflammatory response to respiratory syncytial virus infection in infants with acute bronchiolitis. This contrasts with the predominantly eosinophilic response evident in atopic upper and lower respiratory tract disease.