Discriminators of mouse bladder response to intravesical Bacillus Calmette-Guerin (BCG).

BACKGROUND: Intravesical Bacillus Calmette-Guerin (BCG) is an effective treatment for bladder superficial carcinoma and it is being tested in interstitial cystitis patients, but its precise mechanism of action remains poorly understood. It is not clear whether BCG induces the release of a unique set of cytokines apart from its pro-inflammatory effects. Therefore, we quantified bladder inflammatory responses and alterations in urinary cytokine protein induced by intravesical BCG and compared the results to non-specific pro-inflammatory stimuli (LPS and TNF-alpha). We went further to determine whether BCG treatment alters cytokine gene expression in the urinary bladder. METHODS: C57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-alpha. Morphometric analyses were conducted in bladders isolated from all groups and urine was collected for multiplex analysis of 18 cytokines. In addition, chromatin immune precipitation combined with real-time polymerase chain reaction assay (CHIP/Q-PCR) was used to test whether intravesical BCG would alter bladder cytokine gene expression. RESULTS: Acute BCG instillation induced edema which was progressively replaced by an inflammatory infiltrate, composed primarily of neutrophils, in response to weekly administrations. Our morphological analysis suggests that these polymorphonuclear neutrophils are of prime importance for the bladder responses to BCG. Overall, the inflammation induced by BCG was higher than LPS or TNF-alpha treatment but the major difference observed was the unique granuloma formation in response to BCG. Among the cytokines measured, this study highlighted the importance of IL-1beta, IL-2, IL-3, IL-4, IL-6, IL-10, IL-17, GM-CSF, KC, and Rantes as discriminators between generalized inflammation and BCG-specific inflammatory responses. CHIP/Q-PCR indicates that acute BCG instillation induced an up-regulation of IL-17A, IL-17B, and IL-17RA, whereas chronic BCG induced IL-17B, IL-17RA, and IL-17RB. CONCLUSION: To the best of our knowledge, the present work is the first to report that BCG induces an increase in the IL-17 family genes. In addition, BCG induces a unique type of persisting bladder inflammation different from TNF-alpha, LPS, and, most likely, other classical pro-inflammatory stimuli.

Sarcoidosis associated with acute renal failure and increased levels of interleukin-6 in urine.

A 24-year-old man who had uveitis and showed intrathoracic lymph node swelling on a chest X-ray, was admitted to our hospital for further examination. Transbronchial lung biopsy specimens revealed non-caseating granulomas compatible to sarcoidosis. As the renal function became progressively worse, a specimen was obtained by renal biopsy. It showed a granuloma formation, and was diagnosed as renal sarcoidosis. A high level of interleukin (IL)-6 was detected in his urine. After oral administration of prednisolone, the renal function improved, and the urinary IL-6 level was reduced. These findings suggest that in sarcoidosis associated with renal failure, steroid therapy is effective and that IL-6 plays an important role in the pathogenesis of renal involvement of sarcoidosis.

Urinary excretion of the collagen cross-link pyridinoline increases during liver fibrogenesis.

BACKGROUND/AIMS: Pyridinoline, a specific cross-link of mature collagen, increases in liver during fibrogenesis and its hepatic level is related to the degree of reversibility of the fibrotic process. Since pyridinoline is excreted in urine, we have investigated the relationship between its urinary level and liver fibrogenesis in a model of mild and reversible liver fibrosis, murine schistosomiasis. METHODS: Pyridinoline was measured by HPLC in urine and in liver of Schistosoma mansoni-infected mice during the acute and the chronic phases of the infection. Collagen deposition was measured colorimetrically. Both the isolated granulomas and the surrounding liver parenchyma were analyzed. RESULTS: In infected mice, pyridinoline increased mainly in the isolated granulomas, corresponding to the fibrotic lesions, and slightly in the surrounding parenchyma. The urinary excretion of pyridinoline increased during liver fibrogenesis and was correlated to the duration of infection (r=0.81) and to the collagen content of granulomas (r=0.81). The treatment of infected mice by praziquantel, an antiparasitic drug, did not lead to significant changes in liver collagen cross-linking by pyridinoline either in granulomas or in parenchyma. The major effect of the drug was targeted at the collagen content of parenchyma, which decreased by 50%, 18 weeks after treatment. The urinary level of pyridinoline of treated mice was negatively correlated to the length of the treatment follow-up (r=-0.76). CONCLUSIONS: The measurement of the urinary excretion of pyridinoline could be helpful to monitor the remodeling of liver extracellular matrix occurring in fibrogenesis and the effect of chemotherapy.

Urinary cytology in the diagnosis of renal xanthogranulomatosis.

We present our 4-year experience on the preoperative diagnosis of renal xanthogranulomatosis by sequential urinary cytology. The usefulness of this method is evident due to the absence of any other possible means of preoperative diagnosis of this disease. The possibility of obtaining foam cells by ureteral catheter washouts and translumbar aspiration in the patients, where spontaneous urine cytologies were negative, is also pointed out.

Preoperative diagnosis of renal xanthogranulomatosis by serial urinary cytology: preliminary report.

The search for foam cells in the urinary sediment of patients with possible renal xanthogranulomatosis can constitute a harmless and useful diagnostic method for this frequently occurring renal disease, which previously has been diagnosed with certainty only by histological examination or biopsy. Of 5 cases studied the search was positive in 80 per cent.

Urinary excretion of hydroxylysyl glycosides during acute inflammation in the rat.

1. Subcutaneous inflammatory granuloma were induced in young rats and the urinary excretion of hydroxyproline and hydroxylysyl glycosides was observed during the period of acute inflammation. 2. All collagen metabolites were increased in the urine and excretion of glucosyl-galactosyl-hydroxylysine was much greater than excretion of galactosyl-hydroxylysine in the first days. 3. It is argued that urinary glucosyl-galactosyl-hydroxylysine is probably derived from hydroxylysyl residues of soluble collagen. 4. This study affords new arguments in favour of the dermal origin of urinary glucosyl-galactosyl-hydroxylysine, at least in skin inflammation.