Interstitial cystitis (IC) is a perplexing disease in which pathogenic mechanisms appear to involve immunological and non-immunological inflammatory mediators. A team of investigators with expertise in different disciplines (Interstitial Cystitis Research Group -ICRG) of Scripps Clinic and Research Foundation will seek to identify the inflammatory mediators involved and define the mechanisms which are activated by studying serum, plasma, urine and bladder tissue of IC patients. A clinical core will recruit IC patients into the study, characterize them clinically and obtain plasma, serum, urine and tissue specimens. Clinical material will also be obtained from 4 collaborating urology centers in other parts of the country. Project 1 is an immuno-histopathology core which will use state-of-the-art immunological reagents to characterize cellular infiltrates and immune/inflammatory deposits in bladder tissue. This effort will be supplemented by electron microscopy to identify ultracellular structures. Project 2 will examine the autoimmune response in IC devoting special attention to characterizing the molecular nature of intracellular autoantigens, using immunoprecipitation of isotope-labeled cells, Western blotting and ELISA. Subsequently cDNA cloning of identified autoantigens will be pursued. Project 3 will investigate the mucosal mast cell-IgE system, including mast cell growth and releasing factors which might be present in urine and explore the possibility of IgE and IgG4 antibodies to autoantigens. The other projects (4-6) will focus on inflammatory mediators with project 4 studying mediators which are products of arachidonate metabolism, complement breakdown, platelet activation and cell-associated proteases. The role of the kinin-generating system will be the emphasis of project 5 and will examine participation of vasoactive intestinal peptide (VIP), neurokinins A and B and calcitonin gene related peptide (CGRP). The final section project 6 will address involvement of neuropeptide substance P, interleukin 6 and transforming growth factor b (TGFb), components which are known to be nociceptive or related to autoantibody production and fibrosis. This multidisciplinary approach which is intended to examine inflammatory pathways already suspected or highly likely to be involved in IC is designed to study each patient in several parameters and is anticipated to contribute insights into their relative importance in the disease process.
