Kallikrein – Kinin System and Coagulation System in Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis (UC), are complex disorders characterized by chronic, local and systemic inflammation and spontaneously relapsing course. The causes of these diseases are unknown, however they display genetic and environmental components and appear to be immunologically mediated in part by enteric microbiota (Baumgart & Carding, 2007). There are convincing evidences that IBD are diseases of immunological hyperresponsiveness within the mucosa. Immunological reactions may be directed against luminal bacteria and their products normally present in the intestine (Sartor, 2006). Alternatively, mucosal inflammation in IBD might represent an immune response against unusual antigens such as environmental factors and/or epithelial HLA halotypes. The initiating events may be nonspecific and induce transient injury. The normal response is suppression of inflammation, but genetically susceptible host amplifies the inflammatory response. The activation of intestinal T helper cells (TH1, TH2 and TH17) play a pivotal role in experimental and human IBD because they modulate of the response to enteric microbiota and autoimmunity which is probably critical to IBD chronicity. Crohn’s disease is TH1 and TH17 related disorder with local over-production of interleukin – 2 (IL-2), interpheron ┛ (INF┛), IL 12, and IL-23, whereas in UC it is apparent activation of TH2 lymphocyte cytokine profile, mostly IL-4 and IL-10 as well as IL-13 by natural killer T cells. Interaction of activated T cells with effector cells (macrophages and neutrophils) leads to release of cytokines, eicosanoids and activation of complement cascade and coagulation and kallikrein kinin systems which cause tissue injury. Many cytokines including interleukin 1 (IL-1), tumor necrosis factor (TNF) and IL-8 are increased in both active UC and Crohn’s disease. The tissue levels of arachidonic acid metabolities; prostaglandins,leukotrienes and thromboxanes correlate with gross and histological evidence of intestinal inflammation in IBD. The activation of coagulation has been recognized as important component of the inflammatory response in both Crohn’s disease and UC, and also is significant in progression and possibly pathogenesis of these entities (Danese et al., 2007). A significance the kallikrein – kinin system in human IBD is still uncertain although in animal IBD models kallikreins and kinins have been documented in part to mediate intestinal and systemic inflammation. There are two types of kallikreins, plasma and tissue; both serine protease