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)

Monocytes/macrophages are a prominent feature of the inflammatory infiltrate in inflammatory bowel disease (IBD). Progress in the development of monoclonal antibodies has provided a powerful means to identify and study various subsets of macrophages in the intestinal mucosa. In both Crohn's disease and ulcerative colitis distinct macrophage populations have been found being prominent in active disease, but absent from normal mucosa. Studies of our group show that the Ca(2+)-binding proteins MRP8 and MRP14 as well as their heterocomplex MRP8/14 (27E10 epitope) can be immunolocalized in the majority of granulocytes and macrophages in active but not inactive IBD. Serum MRP8/14 concentrations are significantly increased in patients with active IBD compared with patients suffering from inactive/mild disease. In vitro studies revealed that IL-13, IL-10 and IL-4 strongly suppress secretion of monocytic proteins. Differential responses of monocytes and macrophages towards the inhibitory effects of TH2-cytokines can be observed in both patients with IBD and control groups. Combined treatment with TH2-cytokines may effectively suppress the response of activated monocytes/macrophages thus being of potential therapeutic benefit for patients with IBD.
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PMID:[A system of nonspecific defense in chronic inflammatory bowel diseases--pathophysiologic and therapeutic aspects]. 954 1

The cause of inflammatory bowel diseases is unknown, but T-cells play an important part in the pathogenesis of Crohn's disease. It was shown in recent years that activated T-cells produce certain cytokines that cause inflammation (interferon-alpha, tumour necrosis factor-alpha or TNF-alpha), but also cytokines (interleukin-10 or IL-10, transforming growth factor-alpha) which on the contrary inhibit inflammation. On the basis of this knowledge, the mucosal inflammatory reaction can be counteracted in a rational manner: antibodies against TNF-alpha in most patients with Crohn's disease who failed to respond to corticosteroids led to substantial reduction of disease activity. The first experiences with IL-10 treatment of Chrohn patients are also encouraging. It is expected that in the near future still more forms of immunotherapy directed against cytokines will become available.
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PMID:[Immunology in medical practice. IV. Inflammatory bowel diseases: pathogenic starting points for specific therapy]. 955 Jul 44

Several theories have already been postulated in connection with the pathogenesis of inflammatory bowel diseases, yet none of them has been approved. Recently increasing attention has been payed to different cytokines, playing central role in the development of inflammatory processes. In the intestinal mucosa of patients suffering from inflammatory bowel diseases increasing amounts of interleukin-1 (IL-1), tumor necrosis factor (TNF) and platelet activating factor (PAF) could be measured. On the other hand, antiinflammatory cytokines seem to be ineffective, or being present in insufficient amount (IL-4 and IL-10 respectively). It is therefore probable, that altered ratios of cytokines, or pathologic regulation of their production lead to progression of inflammation in IBD. Influence of cytokine production may open new therapeutic approach, e.g. IL-10 enema proved to be effective in the treatment of some cases of steroid-resistant ulcerative colitis, while intravenous administration was useful in Crohn's disease. A brief, comprehensive review of our present knowledge about cytokines in IBD is given.
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PMID:[The role and significance of the most important known cytokines in inflammatory bowel diseases]. 963 23

Although the importance of genetic susceptibility to IBD has been established by epidemiological studies, the genes involved remain poorly characterized. Important candidate genes include those encoding the immunoregulatory cytokines IL-2 and IL-10. The aim of this study was to assess the contribution of the IL-2 and IL-10 genes to IBD susceptibility. One hundred and ninety-eight pairs of siblings with IBD were genotyped at dinucleotide repeat polymorphisms within the IL-2 and IL-10 genes, and data analysed by the affected sib-pair method of linkage analysis and the transmission disequilibrium test (TDT). A subset of 89 affected sibling pairs was genotyped at markers flanking the IL-2 gene as part of a genome-wide search. The IL-2 polymorphism showed no linkage to IBD overall, but modest evidence for linkage to the ulcerative colitis (UC) data set (P = 0.028). A microsatellite 4 cM distal to the IL-2 gene showed a similar distortion in the ulcerative colitis subgroup (P = 0.006). The TDT showed some distortion of allelic transmission for the IL-2 polymorphism in the UC group, but this did not reach statistical significance (P = 0.09). Results for the IL-10 polymorphism were not significant. Thus the gene encoding IL-2 may contribute to UC susceptibility, but the effect is modest and must await replication in other data sets. The IL-10 gene does not appear to contribute to the risk of developing UC or Crohn's disease.
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PMID:Contribution of the IL-2 and IL-10 genes to inflammatory bowel disease (IBD) susceptibility. 969 79

Inflammatory bowel disease (IBD) denotes chronic inflammatory disorders of gastrointestinal tract of unknown etiology that comprises 2 major groups: ulcerative colitis (UC) and Crohn's disease (CD). Disregulation of the intestinal immune system both at humoral and cellular level constitutes an important element in the multifactorial pathogenesis of IBD. The expression of pro-inflammatory cytokines, most notably IL-1, IL-6, TNF-alpha and chemokines (IL-8, ENA-78, MCP-1, RANTES) in intestinal mucosa from IBD patients is markedly enhanced, however, it is not always accompanied by increases in cytokines' serum levels. In IBD also significant changes occur in the tissue expression of immunoregulatory cytokines: increased levels of IL-2 mRNA and IFN-gamma mRNA, and decreased expression of IL-4 were found in affected intestinal mucosa. Chronic intestinal lesions of patients with Crohn's disease are associated with a Th1 type cytokine profile. The clinical effectiveness of anti-TNF-alpha antibodies and of IL-10 has been demonstrated in steroid-refractory Crohn's disease patients. The data demonstrating the role of cytokines in the pathogenesis of IBD should be carefully analyzed because of limitations imposed by the patient- and sample-related parameters. Further investigations will clarify the significance of the impairments in cytokine network for the initiation and progression of the IBD.
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PMID:Cytokines in inflammatory bowel disease. 970 46

Experimental data indicate that mucosal CD4+ T cells play an important role in the pathogenesis of inflammatory bowel disease (IBD). Based on the pattern of cytokine production, CD4+ T cells may be distinguished into two different phenotypes. Th1 responses are characterized by secretion of interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, lymphotoxin, and interferon (IFN)-gamma and are associated with delayed-type hypersensitivity reactions, whereas Th2 responses, which are characterized by secretion of IL-4, IL-5, and IL-10, have been associated with humoral immune responses and allergy. To assess the number of IFN-alpha and IL-4 positive cells in IBD and normal intestinal specimens, frozen sections from intestinal specimens from 10 Crohn's disease (CD), 8 ulcerative colitis (UC), and 8 healthy controls were examined by immunohistochemistry. Monoclonal antibodies for CD3, CD8, IFN-gamma, and IL-4 were used. T-lymphocyte infiltration and cytokine expression by epithelial, lamina propria, and submucosal cells were scored on a four-point scale by two independent observers who were blinded for the clinical data. One-way analysis of variance (ANOVA) testing was used for statistical analysis. In intestinal specimens from IBD patients, the number of CD3+ cells was found increased in the lamina propria and, within the submucosa, this increase was significant (p < 0.001). In CD the number of lamina propria IFN-gamma positive cells was significantly increased as compared with controls (p < 0.002). In UC the number of both IFN-gamma and IL-4 producing cells in the lamina propria was not significantly increased as compared with controls. The present results confirm the existence of a Th1-biased pattern production in CD but not in UC.
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PMID:Altered expression of interferon-gamma and interleukin-4 in inflammatory bowel disease. 983 81

Inflammatory bowel disease therapy can be considered in several subcategories, and this review is designed to provide selective updates for some of the most important therapeutic entities currently marketed or soon to be available for the medical management of IBD. Although conventional corticosteroids have been a major component of acute inflammatory bowel disease management, steroids have many serious disadvantages; and toxicity is heightened with chronic steroid therapy. Newer corticosteroids, particularly budesonide, may be less toxic than older agents such as prednisone. Budesonide may be used as an enema in active distal ulcerative colitis (UC) or as delayed release tablets in Crohn's disease (CD). However, budesonide is not completely free from steroid side effects, and may share in some of the toxicity of older corticosteroids, particularly when high dose budesonide is administered. Topical and oral aminosalicylates are widely utilized for the treatment of mild to moderate active UC and mild active CD, and they also are efficacious for maintenance of IBD remission. Recent data continue to support the concept that higher doses and prolonged use of mesalamine-based drugs are therapeutically superior to lower doses and short term treatment. In addition, the combination of oral and rectal aminosalicylate formulations often succeeds in patients refractory to either used alone. The immunomodulatory drugs azathioprine and 6-mercaptopurine are particularly effective in treating both CD and UC, and methotrexate has also shown some promise in CD therapy. Immunosuppressive therapy for inflammatory bowel disease initially met with strong physician resistance. However, views have shifted in response to positive data on the utility of immunosuppressive agents in many cases of IBD. Although cyclosporine may be used as a 'rescue' medication in some severe IBD cases, it has been associated with severe toxic reactions. Possible candidates for cyclosporine treatment should be offered such therapy only in academic centers highly experienced with the nuances of this modality. Clinical trials of the newer entities IL-10, IL-11, tacrolimus, and anti-TNFalpha, have demonstrated variable efficacy in refractory IBD patients. Anti-TNFalpha has been very impressive, particularly in the presence of fistulizing Crohn's disease. Many physicians have utilized various antibiotics empirically as part of their 'general' management of IBD. Only metronidazole has been adequately studied in controlled CD trials, but other antibiotic studies are pending. Further exploration of antimicrobial treatment for IBD is clearly warranted. Many other investigational agents in disparate pharmaceutical categories have been employed in IBD therapy; and some of these also show varying degrees of promise, including the aloe vera derivative acemannan, several formulations of heparin, and both transdermal and intra-rectal nicotine. Despite the growing list of medications and formulations promoted for the treatment of IBD, no single drug or recognized combination has yet been confirmed as dependably clinically effective. Many additional investigations of IBD medical therapy are needed, including permutations of conventional medications, along with newer agents that may be more precisely targeted to specific aspects of IBD pathophysiology. All physicians who care for UC and CD patients enthusiastically await more optimal regimens for these challenging disorders.
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PMID:Medical therapy of inflammatory bowel disease for the 21st century. 1002 72

Many immunological abnormalities have been described in inflammatory bowel diseases (IBD). Even though, no clear cut primary defects have yet been described, some therapeutic trials have targeted either immunocompetent cells or overproduction of cytokines. Preliminary results have shown that antisense oligonucleotides (anti-ICAM), anti-cytokine antibodies (anti-TNF) or recombinant human cytokines (IL-10 or IL-11) are effective in some patients with Crohn's disease refractory to steroids. However, these data need to be confirmed and the potential side effects of these treatments must be further considered. These drugs need to be more precisely defined in particular compared to corticotherapy. Finally, data from immunomodulation strategies should help us understand the aetiology of abnormal immune responses in Crohn's disease (CD) and ulcerative colitis (UC).
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PMID:An immunomodulation strategy targeted towards immunocompetent cells or cytokines in inflammatory bowel diseases (IBD). 1021 Jul 67

Inflammatory bowel disease (IBD) is a generic term typically used to describe a group of idiopathic inflammatory intestinal conditions in humans that are generally divided into Crohn's disease and ulcerative colitis. Although the etiology of these diseases remains unknown, a number of rodent models of IBD have recently been identified, all sharing the concept that the development of chronic intestinal inflammation occurs as a consequence of alterations in the immune system that lead to a failure of normal immunoregulation in the intestine. On the basis of these models, it has been hypothesized that the development of IBD in humans may be related to a dysregulated immune response to normal flora in the gut. Immunodeficient scid mice injected with CD4+ CD45RB(high) T cells and mice deficient in interleukin (IL)-10 (IL-10-/-) are among the rodent models of IBD. In both models, there is inflammation and evidence of a Th1-like response in the large intestine, characterized by CD4+ T-cell and macrophage infiltrates, and elevated levels of interferon-gamma. Because IL-10 is an immunomodulatory cytokine that is capable of controlling Th1-like responses, the role of IL-10 was investigated in these models. IL-10 was shown to be important in regulating the development of intestinal inflammation in both models. These results provided key data that supported initiation of clinical trials evaluating the efficacy of IL-10 in patients with IBD.
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PMID:The role of IL-10 in inflammatory bowel disease: "of mice and men". 1036 87

With recent elucidation of pathophysiology and inflammatory process on inflammatory bowel disease(IBD), new drugs and treatments for IBD have developed rapidly. In addition to it, mechanisms of salicylazosulfapyridine, 5-aminosalicylic acid, and glucocorticoid have been clarified at molecular levels as cell transcription factors of NF-kappa B. This paper described the following recent therapy performed in IBD patients; 1)leukocytapheresis by G-column, LCAP and centrifugal separator. 2)cytokine and anti-cytokine therapy with anti-TNF-alpha chimeric monoclonal antibody and IL-10 for treatment of Crohn' disease. 3)therapy with antisense oligonucleotide against ICAM-1 in Crohn's disease, and against p65 subunit of NF-kappa B in TNBS induced colitis in mice. 4)therapy modulating receptor function of target cells. 5)therapy with antibody against cell adhesion molecules. 6)radical scavenger therapy with lipo-SOD. And, 7)treatment with low molecular heparin.
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PMID:[Present states of development in new drugs and treatment of inflammatory bowel disease]. 1057 18


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