Humans ; Animals ; Mice ; NF-kappa B/metabolism* ; Crohn Disease/drug therapy* ; Dextran Sulfate ; Colitis/metabolism* ; Macrophages/metabolism* ; Adenosine Triphosphate/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Colon/metabolism*

No abstract available.
Crohn Disease/*drug therapy/*metabolism ; Female ; Forkhead Transcription Factors/*metabolism ; Gastrointestinal Agents/*therapeutic use ; Humans ; Infliximab/*therapeutic use ; Leukocytes, Mononuclear/*metabolism ; Male ; Membrane Proteins/*metabolism ; beta-Defensins/*metabolism

Inflammatory bowel disease (IBD) is a chronic progressive idiopathic inflammatory disorder that involves the digestive tract from the mouth to the anus. Over the past decades, many therapeutic strategies have been developed to manage IBD, but therapeutic strategies based only on relief of clinical symptoms have not changed the natural history of this disease entity. This underlines the importance of understanding the natural history of IBD itself. When we look at the natural history of Crohn's disease (CD), it first begins with inflammation of the intestinal mucosa and this inflammatory reaction proceeds to stenosing or penetrating reaction if not adequately controlled. However, it takes a considerable amount of time before mucosal inflammation proceeds to stenosis of the intestinal lumen or penetration into the adjacent bowel. Therefore, it can be expected that if proper care is given during that period, progression of CD to such a complicated disease could be prevented. Even though the concept of mucosal healing was introduced in the early 1990s, no correlation could be observed between healing of mucosal lesions and relief of clinical symptoms. However, the introduction of biologic agents targeting tumor necrosis factor has changed the way to treat IBD that is refractory to standard medications and has allowed us to aim for a new therapeutic goal, 'deep remission'. Further advances in biologic agents have provided highly effective treatments for IBD, making deep remission a realistic goal. Whether IBD patients may benefit by experiencing a 'deep' remission beyond the control of clinical symptoms need to be evaluated in further investigation. Nevertheless, it can be anticipated that attaining deep remission might ultimately have an impact on important outcomes such as the need for surgery and the quality of life.
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Colitis, Ulcerative/drug therapy/metabolism/pathology ; Crohn Disease/drug therapy/metabolism/pathology ; Humans ; Inflammatory Bowel Diseases/drug therapy/metabolism/*pathology ; Intestinal Mucosa/metabolism/pathology ; Mesalamine/therapeutic use ; Tumor Necrosis Factor-alpha/immunology/metabolism

BACKGROUND/AIMS: This study investigated the expression of T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3), human beta-defensin (HBD)-2, forkhead box protein 3 (FOXP3), and the frequency of CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) in children with Crohn's disease (CD) during infliximab therapy. METHODS: We enrolled 20 CD patients who received infliximab treatment for 1 year. Peripheral blood and colonic mucosal specimens were collected from all CD patients and from healthy control individuals. RESULTS: A significant difference in TIM-3 mRNA expression was evident in peripheral blood mononuclear cells and colonic mucosa between CD patients before infliximab therapy and the healthy controls (p<0.001 and p=0.005, respectively). A significant difference in HBD-2 mRNA expression was found in colonic mucosa between CD patients before infliximab therapy and the healthy controls (p=0.013). In the active phase of CD, at baseline, the median percentage of T cells that were CD25+ FOXP3+ was 1.5% (range, 0.32% to 3.49%), which increased after inflixmab treatment for 1 year to 2.2% (range, 0.54% to 5.02%) (p=0.008). CONCLUSIONS: Our study suggests that both the adaptive and innate immune systems are closely linked to each other in CD pathogenesis. And the results of our study indicate that it could be a useful therapeutic tool, where restoration of TIM-3, HBD-2 and the function of Tregs may repair the dysfunctional immunoregulation in CD.
Adolescent ; Case-Control Studies ; Colon/immunology ; Crohn Disease/*drug therapy/immunology/*metabolism ; Female ; Forkhead Transcription Factors/*metabolism ; Gastrointestinal Agents/*therapeutic use ; Humans ; Infliximab/*therapeutic use ; Intestinal Mucosa/immunology ; Leukocytes, Mononuclear/*metabolism ; Male ; Membrane Proteins/*metabolism ; T-Lymphocytes, Regulatory/immunology ; beta-Defensins/*metabolism