The development of adhesions associated with abdominal and gynecologic surgical procedures causes severe morbidity and can be fatal. These structures are also associated with infertility and chronic pelvic pain in women. The treatment of complications stemming from surgical adhesion formation represents a significant burden to the healthcare system in the United States costing an estimated 1-2 billion dollars per year. Currently, there are a limited number of therapeutic options available to prevent their development. The immunopathogenesis of adhesion formation is poorly understood and relatively little is known regarding the cellular host response responsible for their development. It is believed that these structures form as a result of a breakdown in the balance between the molecular events leading to the deposition of fibrin in the normal peritoneal wound healing response and the fibrinolytic pathway that restores the integrity of mesothelial tissue. Preliminary studies from our laboratory have shown that CD4+ T cells are critical to the pathogenesis of abdominal surgical adhesions in two different animal models of this host response. These data are the first to show a definitive role for this cell type in adhesiogenesis. Based on this work, we hypothesize that T cells, through the release of T cell-derived cytokines and chemokines, have a central role in orchestrating the inflammatory process leading to the development of surgical adhesions. We propose to test this hypothesis by determining: 1) the specific T cell subset(s) that govern adhesion formation; 2) the role of T cell activation and costimulation in mediating this response; and 3) the cytokines and chemokines that control adhesion formation. There is currently very little known regarding the role of T cells in adhesion formation. Results from these studies will define a new paradigm for understanding the pathogenesis of surgical adhesion formation and identify new cellular targets for the development of compounds that can be used for their prevention.
| Tzianabos, Arthur; Wang, Julia Y; Kasper, Dennis L (2003) Biological chemistry of immunomodulation by zwitterionic polysaccharides. Carbohydr Res 338:2531-8 |
| Chung, Doo Ryeon; Chitnis, Tanuja; Panzo, Ronald J et al. (2002) CD4+ T cells regulate surgical and postinfectious adhesion formation. J Exp Med 195:1471-8 |
