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)

Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) of unknown etiology. They are characterized by an activation of intestinal mononuclear cells. Cytokines play a crucial role in the regulation of the functions of these cells. An increased synthesis of the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha), which are primarily synthesized by activated monocytes/macrophages has been described in patients with IBD. The synthesis of interleukin-2 (IL-2) and of interferon gamma (IFN gamma), which are produced by lymphocytes, on the other hand, has been found to be decreased. The published data are, however, not quite consistent. In patients with IBD there is not only a stimulation of the local cytokine production in the gut. The blood levels and the synthesis of the cytokines IL-1, IL-6 and TNF alpha by peripheral blood mononuclear cells are also increased, in particular in patients with Crohn's disease. Drugs, which are commonly used for the treatment of IBD impair the synthesis of these cytokines in monocytes/macrophages.
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PMID:Inflammatory mediators in chronic inflammatory bowel diseases. 179 95

The spontaneous induced release of interferon gamma (IFN gamma) by cultured intestinal lamina propria lymphocytes was investigated in patients with Crohn's disease. In contrast to normal lymphocytes, intestinal lymphocytes from these patients spontaneously released IFN gamma and seemed to contain IFN gamma in their cytoplasm. Autologous peripheral lymphocytes did not release IFN gamma. When stimulated with interferon inducers lamina propria lymphocytes from Crohn's disease tissue showed an increase in IFN gamma release 24 hours after induction with no appreciable further increase over the next two days of culture, while in control cells, either peripheral or intestinal, IFN gamma release progressively increased, peaking 72 hours after induction. These findings indicate that in Crohn's disease the intestinal lymphocytes are stimulated in vivo to produce IFN gamma and that the spontaneous IFN gamma production is compartmentalised to the gut lymphocytes. These data support the concept that locally released IFN gamma has a crucial role in cell interactions in the lamina propria and contribute to the locally occurring immune phenomena in Crohn's disease, including the increased epithelial expression of major histocompatibility complex class II antigens.
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PMID:Spontaneous release of interferon gamma by intestinal lamina propria lymphocytes in Crohn's disease. Kinetics of in vitro response to interferon gamma inducers. 190 8

In a previous study using total mononuclear cells and lymphocytes, enriched by elutriation centrifugation, of patients with Crohn's disease and ulcerative colitis were found to have a decreased NK cell activity. In the present study the relation with disease activity and treatment, and the effect of recombinant gamma-interferon (gamma-IFN) on NK cell and monocyte cytotoxicity has been studied in 19 patients with Crohn's disease, 11 with ulcerative colitis, two with indeterminate colitis and 12 healthy controls. Patients with active Crohn's disease and active ulcerative colitis were shown to have an impaired NK cell activity compared to the control group. However, no difference was found in the percentage of CD16 (Leu 11+) cells, as determined by fluorocytometry, between patients with active or inactive disease. Moreover, the NK cell impairment was not related to corticosteroid treatment. Recombinant gamma-interferon (gamma-IFN) stimulated significantly the cytotoxic activity of the total mononuclear cells and the monocyte-enriched fraction against all target cell lines, both in patients and controls. No relation was found between the increase in cytotoxicity by gamma-IFN and disease activity in the patients. Stimulation with gamma-IFN demonstrated that the monocyte cytotoxic response of inflammatory bowel disease patients is normal. The present study reveals that the impairment in NK cell activity in patients with inflammatory bowel disease is related to disease activity and therefore suggests to be secondary to the inflammatory process.
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PMID:In vitro cellular cytotoxicity in Crohn's disease and ulcerative colitis: relation with disease activity and treatment, and the effect of recombinant gamma-interferon. 251 28

To investigate the monocyte/macrophages function in patients with Crohn's disease (CD), phagocytosis, monocyte polykaryon formation and accessory cell function were studied. The number of yeast particles/monocyte in patients with CD was significantly higher (p less than 0.005) than that in healthy donors (HD). A significant increase (p less than 0.01) of fusion index was shown in CD patients in the absence of recombinant gamma-interferon (IFN gamma), while only a small amount of fusion was seen in HD. Accessory cell function of the monocytes from patients with CD was reduced, but 3H-thymidine incorporation was increased when the lymphocytes from patients with CD were cultured with the monocytes from HD. These results suggest that peripheral blood monocytes from patients with CD have abnormal functions, which may be involved in the pathogenesis of the granuloma and giant cell formation in CD patients.
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PMID:Impaired monocyte macrophages function in patients with Crohn's disease. 296 48

Using metabolic labeling techniques in human intestinal epithelial cell lines in tissue culture and in situ hybridization techniques in normal and inflamed (Crohn's) intestine, recent studies have shown that there is synthesis of acute phase proteins in enterocytes. Moreover, these studies have shown that acute phase protein biosynthesis in enterocytes is regulated by inflammatory cytokines in a manner characteristic of the physiologic acute phase response. In the course of these studies it was noticed that one inflammatory cytokine, interleukin-6 (IL-6), mediated selective down-regulation of the enterocyte-specific, differentiation-dependent integral membrane protein sucrase-isomaltase (SI) in the Caco2 intestinal epithelial cell line. In the current study we examined the effect of several other inflammatory cytokines interleukin-1 (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interferon gamma (IFN gamma) on synthesis of SI in Caco2 cells, examined the possibility that inflammatory cytokines affect the synthesis of other enterocyte integral membrane proteins using lactase as a prototype, and examined the possibility that SI gene expression was down-regulated in villous enterocytes in vivo during the local inflammatory response of Crohn's disease. The results show that IL-6 and IFN gamma each mediate a decrease and TNF alpha mediates an increase in synthesis of SI in Caco2 cells. The magnitude of down-regulation by IL-6 and IFN gamma is significantly greater than the up-regulation by TNF alpha. IL-1 beta has no effect on synthesis of SI. Synthesis of lactase is not affected by any of the cytokines. There is a marked specific decrease in SI gene expression in villous enterocytes in acutely inflamed Crohn's ileum as compared to adjacent uninflamed ileum and normal ileum. Taken together, these data show that inflammatory cytokines have specific and selective effects on the expression of the brush border hydrolase SI in tissue culture and in vivo and provide evidence for a previously unrecognized mechanism for disaccharidase deficiency in intestinal inflammation.
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PMID:Regulation of sucrase-isomaltase gene expression in human intestinal epithelial cells by inflammatory cytokines. 855 56

Cytokines play an important role in the pathology of inflammatory bowel disease by determining the nature of the mucosal immune response. One way of establishing whether CD and UC are causally related to a defect in the host immune response is to look for polymorphisms that are over-represented in these populations. This is being carried out at great pace both for the cytokine genes and for some other immune response genes. A number of gene expression studies have established that those cytokines produced by activated macrophages such as IL-1, IL-6 and TNF are significantly elevated in both diseases. Differences between the two diseases are less clear, and, where they have been found, they probably reflect the accuracy and sensitivity of quantification. The picture is less clear for the T-cell-derived cytokines, which are generally expressed at a lower copy number in intestinal tissue compared to the monokines. For Crohn's disease, the TH1 cytokines IL-2 and IFN may be abnormally elevated or decreased. In contrast, the TH1/TH2 profile in UC is not significantly different from normal controls. Further work is required to confirm these findings.
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PMID:Cytokines and inflammatory bowel disease. 873 6

Eosinophils are not only the source of cytotoxic and proinflammatory mediators but they can also generate cytokines and growth factors, including their own factors of differentiation, namely IL-3, GM-CSF, and IL-5. Synthesis of IL-5 by eosinophils was demonstrated by in situ hybridization and immunostaining in a variety of diseases, such as coeliac disease, asthma, hypereosinophilic syndrome, or skin diseases. However, IL-5 synthesis by eosinophils was not shown in Crohn's disease, whereas in other diseases, it was restricted to a subpopulation of eosinophils, suggesting some heterogeneity in cytokine-producing eosinophils. Here, we report that human eosinophils, in addition to the synthesis of IL-5, and Th2 cytokine, can synthesize IFN gamma, a Th1 cytokine, as well as IL-10 and IL-4, known to be mainly produced by Th2 cells. Double immunostaining procedures reveal the coexpression of IL-5, IL-4, and IL-10 by the same eosinophil populations, different from IFN gamma-producing eosinophils. We propose that distinct subpopulations of human eosinophils express Th2 or Th1 cytokines. These results point to the importance of cytokines derived from non T cells in the regulation of the immune response.
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PMID:Synthesis of type 1 (IFN gamma) and type 2 (IL-4, IL-5, and IL-10) cytokines by human eosinophils. 890 27

Antineutrophil cytoplasmic antibodes (ANCA) are markers of necrotizing vasculitis. ANCA have been recently detected in the two forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD). To assess the possible role of ANCA in the diagnosis and management of IBD we studied the prevalence of ANCA at diagnosis and during follow-up in a group of 89 IBD patients. The relationship between ANCA and clinical features of IBD was investigated. ANCA assayed by indirect immunofluorescence were detected in 38/52 (73%) of the UC patients but only 6/37 (16.6%) of the CD patients (P<0.005) and in none of the controls. In the UC group, but not in the CD group, there was a positive correlation between ANCA and disease activity. The sensitivity and specificity of ANCA for the diagnosis of UC were 73 and 83.7% respectively. The most commonly observed pattern of ANCA in IBD patients was perinuclear: in 84% of the UC and 66.6% of the CD patients positive for ANCA, respectively. However, careful comparison of IFL patterns revealed some distinct features of IBD-associated ANCA when compared to vasculitis-associated ANCA. In addition, most ANCA positive sera from IBD patients were negative for antibodies to proteinase 3 and myeloperoxidase by ELISA. These results suggest that the autoantigens recognized by ANCA are different in patients with IBD from those with necrotising vasculitis.
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PMID:Relationship between ANCA and clinical activity in inflammatory bowel disease: variation in prevalence of ANCA and evidence of heterogeneity. 918 79

The intestinal epithelial cell population is comprised of a dynamic continuum, ranging from undifferentiated, actively proliferating crypt cells, to mature absorptive villus enterocytes, lacking mitotic capacity. Under normal conditions, the constant loss of differentiated villus tip cells via apoptosis leads to a complete renewal of the epithelial cell population every few days. The physiological factors regulating enterocyte proliferation, maturation and apoptosis in health, as well as those that modulate these events in disease states remain largely unknown. It has been demonstrated in vitro that immature crypt cell proliferation is stimulated by factors such as TGF alpha and TNF alpha, whereas TFG beta and IFN gamma inhibit mitotic activity. Further studies showed that intestinal epithelial cells are able to produce and secrete several cytokines such as IL6, IL8, TNF alpha, TGF alpha and TGF beta, indicating the potential for autocrine and paracrine responses. A variety of immune mediated bowel disorders, including celiac disease, Crohn's disease and ulcerative colitis, are characterized by accelerated epithelial cell turnover and apoptosis, leading to altered crypt/villus morphology. There is increasing evidence that these changes, and the accompanying functional alterations of the bowel epithelium, are mediated by the cytokines released from infiltrating inflammatory cells, as well as from enterocytes themselves in an autocrine fashion.
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PMID:Cytokine--intestinal epithelial cell interactions: implications for immune mediated bowel disorders. 955 84

Cytokines are important protein mediators of immunity, inflammation, cell proliferation, differentiation, fibrosis, etc. (Oppenheim and Saklatvala, 1993). As these are the major biological processes underlying autoimmunity, it is not surprising that there is now convincing evidence that cytokines have an important role in the pathogenesis of autoimmunity (Brennan and Feldmann, 1996; Feldmann et al., 1996). There has been much progress since we first highlighted the role of cytokines such as IFN gamma in autoimmunity in the early 1980s (Bottazzo et al., 1983). The number of cytokines molecularly cloned has increased greatly, and the biochemical and structural basis of their action are partly understood, as cytokine genes and that of their receptors have been cloned. Knowledge of cytokine signalling is rapidly expanding (see Chapter XIII). In medical terms, clear evidence of the importance of cytokines in autoimmunity is demonstrated by therapeutic advances. Thus it is possible to dramatically improve patients with rheumatoid arthritis and Crohn's disease by blocking TNF alpha, and a new target for therapy, TNF alpha, has thus been validated for both these diseases.
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PMID:Cytokines in autoimmune disorders. 991 49


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