Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010346 (Crohn's disease)
 21,615 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical studies indicate an important role for bowel inflammation in ankylosing spondylitis and other spondyloarthropathies whereby two different aspects have to be considered. First, the gut inflammation is clinically and histologically closely related to Crohn's disease. Recent data on subclinical immune alterations confirm this relationship and suggest that spondyloarthropathy is a unique human model for studying early Crohn's disease. Second, bowel and peripheral joint inflammation are clinically, histologically and pathogenetically linked. The most important clinical implication of these observations is that targeted therapies for Crohn's disease could also be effective for intestinal as well as extra-intestinal disease manifestations in spondyloarthropathy, as evidenced by the recent studies on TNF-alpha blockade. Unravelling the gut-synovium axis in spondyloarthopathy could also contribute to the identification of new therapeutic targets. Finally, assessment of subclinical gut inflammation by histology, serology and genetics could contribute to the stratification of individual patients in subgroups with an optimal response to specific therapeutic interventions.
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PMID:Ankylosing spondylitis and bowel disease. 1240 26

Human cathepsin W (lymphopain) is a cysteine protease that is restrictively expressed in cytotoxic cells, in particular NK cells. Several anti-cathepsin W monoclonal antibodies were tested with respect to their capability to detect cathepsin W by Western blot analysis and immunohistochemistry. Subsequently, the distribution of cathepsin W-expressing cells was studied in gastrointestinal tissue specimens using the antibody CW-401B1. All cathepsin W-positive cells had a 'lymphocyte phenotype'. Notably, samples from patients suffering from chronic inflammatory bowel disease (Crohn's disease, CD; ulcerative coliltis, UC) or autoimmune gastritis revealed variable amounts of cathepsin W-expressing cells. The relative portion of cathepsin W-positive cells among the infiltrating leukocytes (determined by CD45) differed remarkably. In autoimmune gastritis, cathepsin W-expressing cells made up for 65% of all CD45+ cells, whereas the corresponding values for CD and UC were 11% and 6%, respectively. These differences imply a distinct involvement of cytotoxic cells expressing cathepsin W in the pathogenesis among these diseases. Furthermore, it was tested whether the pro-inflammatory cytokines TNF-alpha and IFN-gamma can regulate cathepsin W gene expression in NK-92 cells. Both pro-inflammatory cytokines had only little effect on the cathepsin W gene expression of these cells.
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PMID:Characterization of novel anti-cathepsin W antibodies and cellular distribution of cathepsin W in the gastrointestinal tract. 1243 18

Spondyloarthropathies are characterized by both axial and peripheral joint involvement, by the association with "other diseases" mainly Psoriasis, Crohn's and Anterior Uveitis and by the high prevalence of HLA B-27. While disease modifying drugs, such as Methotrexate or Sulfasalazine, are only partially effective in controlling peripheral arthritis, the treatment of the axial part remained only symptomatic. The recently introduced anti-TNF-alpha drugs Infliximab (Remicade) and Etanercept (Enbrel) for the treatment of Crohn's disease and Rheumatoid Arthritis has been expended to Spondyloarthropathies with highly promising results. The rationale and the early beneficial results of this new approach in spondyloarthropathies are reviewed.
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PMID:[Anti-TNF-alpha treatment and spondyloarthropathies]. 1247 31

Although the cytokine network plays a key role in the inflammatory responses in inflammatory bowel disease, no comprehensive analysis of the intestinal cytokine network has been reported. We analyzed messenger RNA levels for various cytokines in human intestine by real-time quantitative polymerase chain reaction to clarify the cytokine profiles involved in the pathogenesis of inflammatory bowel disease. Biopsy specimens were obtained from 23 patients with ulcerative colitis (15 men, 8 women, mean age of 44.1 years), 17 patients with Crohn's disease (15 men, 2 women, mean age of 21.6 years), and 8 normal controls (6 men, 2 women, mean age of 62.7 years) who underwent colonoscopy for suspected colonic disease. Messenger RNA was isolated from two biopsy samples and reverse-transcribed to obtain cDNA. Mucosal mRNA levels for IL-1beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-gamma and TNF-alpha were simultaneously analyzed by real-time quantitative polymerase chain reaction. In patients with active ulcerative colitis, IL-1beta, IL-4, IL-5, IL-8, IL-12p40, IFN-gamma and TNF-alpha mRNA levels were significantly higher than those in controls. In patients with active Crohn's disease, IL-1beta, IL-8, and IL-12p40 mRNA levels were significantly higher than those in controls. Mucosal level of IL-12p40 mRNA was significantly higher in patients with inactive Crohn's disease than in controls. Both Th1 and Th2 cytokine mRNA levels were increased in colonic mucosa of patients with ulcerative colitis suggesting the possibility that cellular and humoral immunity play roles in the pathogenesis of this disease. In patients with Crohn's disease, Th1 cytokine mRNA levels were increased in colonic mucosa, suggesting predominance of cellular immunity in the pathogenesis of this disease.
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PMID:Comprehensive analysis of intestinal cytokine messenger RNA profile by real-time quantitative polymerase chain reaction in patients with inflammatory bowel disease. 1252 73

Crohn's disease is a chronic inflammation that may involve the entire gastrointestinal tract, from the mouth to the anus. The most widely accepted etiologic theory involves an immunologic aberration leading to local tissue destruction. Cell-mediated immunity with increased tumor necrosis factor (TNF) production may play a role in mucosal damage. Oral and laryngeal involvement are rare manifestations of Crohn's disease that are usually treated successfully by steroids. We here report a rare case of extra-intestinal Crohn's disease resistant to steroid therapy, which was successfully treated with infliximab, a chimeric antibody directed against TNF-alpha that is the only registered agent for the treatment of Crohn's disease. The relative safety, efficacy, and efficiency of infliximab make it an alternative treatment of which otolaryngologists should be aware.
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PMID:New therapy for orolaryngeal manifestations of Crohn's disease. 1253 56

The MAP kinase p38 is implicated in the release of the pro-inflammatory cytokines TNF-alpha and IL-1 beta. Inhibition of cytokine release may be a useful treatment for inflammatory conditions such as rheumatoid arthritis and Crohn's disease. A novel series of imidazopyrimidines have been discovered that potently inhibit p38 and suppress the production of TNF-alpha in vivo.
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PMID:Imidazopyrimidines, potent inhibitors of p38 MAP kinase. 1256 27

Several biological therapies (monoclonal antibodies, designer molecules, recombinant cytokines) have been tested for clinical efficacy in inflammatory bowel disease, and some have been found to be effective. Anti-TNF-alpha (anti-tumour necrosis factor-alpha) antibody therapy is an important treatment modality in the treatment of active and fistulating Crohn's disease and should be considered in patients who fail standard medical therapies. Treatment with TNF-alpha-neutralizing antibodies is associated with immunosuppression that may lead to opportunistic infections and reactivation of tuberculosis, and patients should undergo Mantoux testing prior to treatment. Several other monoclonal antibodies, including anti-IL12 and anti-IFN-gamma, are currently in development for Crohn's disease. Other new approaches include ex vivo generation of regulatory T lymphocytes and antibodies that target and kill (subpopulations of) memory T lymphocytes.
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PMID:New biological therapies in inflammatory bowel disease. 1261 87

Interaction of OX40 (CD134) on T cells with its ligand (OX40L) on antigen-presenting cells has been implicated in pathogenic T cell activation. This study was performed to explore the involvement of OX40/OX40L in the development of T cell-mediated chronic colitis. We evaluated both the preventive and therapeutic effects of neutralizing anti-OX40L MAb on the development of chronic colitis in SCID mice induced by adoptive transfer of CD4(+)CD45RB(high) T cells as an animal model of Crohn's disease. We also assessed the combination of anti-OX40L and anti-TNF-alpha MAbs to improve the therapeutic effect. Administration of anti-OX40L MAb markedly ameliorated the clinical and histopathological disease in preventive and therapeutic protocols. In vivo treatment with anti-OX40L MAb decreased CD4(+) T cell infiltration in the colon and suppressed IFN-gamma, IL-2, and TNF-alpha production by lamina propria CD4(+) T cells. The combination with anti-TNF-alpha MAb further improved the therapeutic effect by abolishing IFN-gamma, IL-2, and TNF-alpha production by lamina propria CD4(+) T cells. Our present results suggested a pivotal role of OX40/OX40L in the pathogenesis of T cell-mediated chronic colitis. The OX40L blockade, especially in combination with the TNF-alpha blockade, may be a promising strategy for therapeutic intervention of Crohn's disease.
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PMID:Therapeutic effect of anti-OX40L and anti-TNF-alpha MAbs in a murine model of chronic colitis. 1263 59

Ulcerative colitis (UC) and Crohn's disease (CD) comprise a series of inflammatory bowel disease (IBD) resulting from chronic upregulation of the mucosal immune system. Although the pathogenesis of IBD remains elusive, it appears that there is chronic activation of the immune and inflammatory cascade in genetically susceptible individuals. Current disease management guidelines have therefore focused on the use of antiinflammatory agents, aminosalicylates and corticosteroids. However, some patients are still refractory to these therapies. Recent advances in the understanding of the pathophysiological conditions of IBD have provided new immune system modulators as therapeutic tools. Cytapheresis has demonstrated effectiveness against UC and has practical use in Japan. Immunosuppressive agents including cyclosporin A and tacrolimus (FK506) have expanded the choice of medical therapies available for certain subgroups of patients. Furthermore, biological therapies have begun to assume a prominent role. Studies with chimeric monoclonal anti-TNF-alpha antibody treatment of CD have been reported with dramatic success. Another antiinflammatory cytokine therapy includes anti-IL-6 receptor, anti-IL-12, or toxin-conjugated anti-IL-7 receptor. Given the diversity of proinflammatory products under its control, NF-kappa B may be viewed as a master switch in lymphocytes and macrophages, regulating inflammation and immunity. In the murine 2,4,6-trinitrobenzen sulfonic acid (TNBS) colitis model, an antisense oligonucleotide to NF-kappa B p65 ameliorated inflammation even after induction of colitis. Recently, a clinical pilot trial of this agent demonstrated promising results. Accumulating evidence suggests that luminal bacterial flora is a requisite and central factor in the development of IBD. Probiotic therapies such as a nonpathogenic Escherichia coli strain have been well tolerated, but larger clinical trials are needed. In addition, novel therapeutic strategies targeting adhesion molecules and costimulatory molecules, or enhancing tissue repair, are under investigation. Although some still need more confirmatory studies, these immune therapies will provide new insights into cell-based and gene-based treatment against IBD in the near future.
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PMID:Introduction and overview: recent advances in the immunotherapy of inflammatory bowel disease. 1269 69

Infliximab is an antibody to tumor necrosis factor (TNF) that is used in the treatment of Crohn disease and rheumatoid arthritis. This medication neutralizes TNF-alpha by binding to TNF receptors and inhibiting further induction of proinflammatory cytokines. We describe a patient with Crohn disease who developed hypersensitivity vasculitis with biopsy-proven leukocytoclastic vasculitis 9 days after her initial dose of infliximab. To our knowledge, this is the first reported case of infliximab-induced hypersensitivity vasculitis with leukocytoclastic vasculitis that occurred after the first dose of drug. It is important to note that hypersensitivity vasculitis can occur secondary to administration of this drug, even after the initial exposure.
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PMID:Hypersensitivity vasculitis with leukocytoclastic vasculitis secondary to infliximab. 1270 83


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