Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Tumour necrosis factor is a proinflammatory macrophage-derived polypeptide cytokine. Its participation in disease processes has been usually inferred from data obtained from experiments in vitro or from measurements of its plasma circulating levels. To investigate its role in chronic ulcerative colitis, we have quantified in vivo the steady-state release of tumour necrosis factor into the colonic lumen. 2. We studied 19 patients with untreated active ulcerative colitis and seven patients with irritable bowel syndrome as controls. A group of seven patients with active ulcerative colitis were studied before and after 4 weeks on treatment with oral 5-aminosalicylic acid. By means of an intracolonic double-lumen perfusion tube, an isotonic solution was continuously infused 50 cm from the anal verge at a rate of 5 ml/min, and was recovered 30 cm distally by siphonage. Effluents were assayed for tumour necrosis factor by a specific e.l.i.s.a. and for prostaglandin E2 and leukotriene B4 by specific r.i.a.s. 3. The intracolonic release of tumour necrosis factor was undetectable in patients with irritable bowel syndrome, whereas measurable release occurred in 15 out of 19 patients with active ulcerative colitis (P < 0.01). Prostaglandin E2 and leukotriene B4 release were also increased in active ulcerative colitis by comparison with irritable bowel syndrome (P < 0.01). Five out of seven patients with colitis improved with 5-aminosalicylic acid treatment, and tumour necrosis factor release became undetectable or decreased markedly (P < 0.05 compared with before treatment). However, tumour necrosis factor release remained high in the non-responder patients. 4. These findings indicate that intracolonic immunoreactive tumour necrosis factor release is enhanced in active chronic ulcerative colitis, becoming undetectable when mucosal lesions are healed. These results suggest that the luminal release of tumour necrosis factor may serve as an objective index of inflammatory activity in patients with chronic ulcerative colitis.
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PMID:Intraluminal colonic release of immunoreactive tumour necrosis factor in chronic ulcerative colitis. 783 99

Microbial metabolites may influence the metabolic integrity of intestinal epithelial cells and induce mucosal immune responses. Therefore, we investigated the effects of the microbial metabolites butyrate, iso-valerate, and ammonium on Caco-2 cells and macrophages. Barrier functioning was determined by measuring transepithelial electrical resistance and basolateral recoveries of metabolites. The barrier function of Caco-2 cells remained intact after exposures. Basolateral recoveries ranged from 6.2% to 15.2%. Tumour necrosis factor-alpha and interleukin-10 were measured to determine immune reactions. The Caco-2 cells did not secrete both cytokines. Physiological concentrations of butyrate and iso-valerate stimulated the secretion of tumour necrosis factor-alpha and suppressed the secretion of interleukin-10 by macrophages that are not protected by an epithelial barrier. In contrast, ammonium concentrations as high as those produced by microbiotas of IBD patients suppressed the release of both cytokines when the barrier function is impaired.
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PMID:The influence of microbial metabolites on human intestinal epithelial cells and macrophages in vitro. 1593 78

The mechanisms leading to positive effects of probiotics in irritable bowel syndrome and inflammatory bowel disease have not been clarified, but the possible involvement of cell wall components is widely discussed. Reduction of the D-alanine content of lipoteichoic acid (LTA) in Lactobacillus plantarum (Dlt(-) mutant) enhanced its anti-inflammatory properties in a mouse colitis model. Another lactobacillus species inhibited visceral pain perception in response to colorectal distension (CRD) in rats. Therefore, we investigated if LTA modification influences the constitutive intestinal pain perception in addition to modulation of cytokine release. Male Sprague-Dawley rats were gavaged with L. plantarum, L. plantarum Dlt(-) mutant or buffer control, respectively and the responses to CRD were tested in this non-inflammatory model. Tumour necrosis factor (TNF), interferon (IFN)-gamma and interleukin (IL)-10 release were measured in colon tissue homogenates and upon anti-CD3/CD28 activation of isolated splenocytes and mesenteric lymphocytes. Control animals showed significant bradycardia following noxious CRD, whereas only the L. plantarum Dlt(-) mutant inhibited the response. The mutant also decreased the activation-induced release of TNF and IFN-gamma from mesenteric T cells and the IL-10 concentration in colonic tissue, while increasing the activation-induced secretion of IL-10 in splenocytes and mesenteric lymphocytes and the baseline IL-10 release of splenocytes. In conclusion, d-alanine depletion of LTA in L. plantarum inhibited visceral pain perception in healthy, non-inflamed rats. Regardless of the non-inflammatory nature of the model decreased visceral pain perception was seen in parallel with anti-inflammatory properties.
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PMID:The D-alanine content of lipoteichoic acid is crucial for Lactobacillus plantarum-mediated protection from visceral pain perception in a rat colorectal distension model. 1831 44

New evidence points to a possible association of multiple sclerosis (MS) with IBD. Tumour necrosis factor (TNF) is involved in the pathogenesis of MS. Paradoxically, administration of anti-TNF monoclonal antibodies to IBD patients has led to exacerbation of MS or triggered demyelination. TNF receptor 1 (TNFR1) mediates demyelination and TNFR2 mediates remyelination, suggesting that a more selective approach to TNF antagonism may be required for an anti-TNF strategy to be effective in MS. Conversely, interferon treatment for MS may worsen IBD. Anti-lymphocyte trafficking strategies such as alpha4 integrin blockers are effective in both these diseases. Recent advances in small molecule development in this area may provide further effective therapies. Common inflammatory cytokine and signaling pathways may be shared between MS and IBD, such as TNF, interleukin (IL)-12/23, IL-17, CD40 and STAT3. However, in contrast to Crohn's disease, ustekinumab has not shown efficacy in MS. Vitamin D deficiency is a hot topic in both diseases. Several drugs developed for MS, e.g. glatiramer acetate, are also being studied in IBDs. As in rheumatoid arthritis, MS also serves as an example of a chronic relapsing inflammatory disease where disease modification is the goal of treatment based on objective evidence derived from imaging, in turn providing examples of how to conduct IBD studies in future.
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PMID:Biologic therapies: lessons from multiple sclerosis. 2279 1