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Articles in PresS, published online ahead of print February 12, 2002
Physiol Genomics, 10.1152/physiolgenomics.00117.2001
Submitted on December 17, 2001
Accepted on February 11, 2002
1 Neurology, University of Vermont, Burlington, VT, USA
2 Neurology, University of Vermont, Burlington, VT, USA; Anatomy and Neurobiology, University of Vermont, Burlington, VT, USA
* To whom correspondence should be addressed. E-mail: mvizzard{at}zoo.uvm.edu.
Cyclophosphamide (CYP)-induced cystitis alters micturition function and produces reorganization of the micturition reflex. This reorganization may involve cytokine expression in the urinary bladder. These studies have determined candidate cytokines in the bladder that may contribute to the reorganization process. A ribonuclease protection assay was used to measure changes in rat bladder cytokine mRNA (interferon (IFN)-gamma, interleukin (IL)-1 alpha/-beta, IL-2, IL-3, IL4, IL-5, IL-6, IL-10, tumor necrosis factor (TNF)-alpha/-beta) after acute (4 hr), intermediate (48 hr) or chronic (10 day) cystitis. The correlation between bladder cytokine mRNA and protein expression was also determined by immunoassay. Although at each time point after cystitis significant changes in bladder cytokine mRNA were observed, the magnitude differed (acute>intermediate>chronic). Acute cystitis demonstrated the most robust changes (p 
0.005; IL-1-beta, 330-fold increase; IL-2, 20-fold increase; IL-4, 8-fold increase; IL-6, 80-fold increase) in cytokine mRNA expression and TNF-alpha/ or TNF-beta mRNA were only increased (2-10-fold) after acute cystitis. More modest increases in cytokine mRNA expression were observed after 48 hr or 10 day cystitis. Cytokine protein expression generally paralleled that of mRNA. Increased cytokine expression after CYP-induced cystitis, alone or in combination with other inflammatory mediators or growth factors, may contribute to altered lower urinary tract function after cystitis.
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