Serum concentrations of tumour necrosis factor alpha in childhood chronic inflammatory bowel disease.

Murch, Simon; Lamkin, V A; Savage, Martin O.; Walker-Smith, J A; MacDonald, Thomas T.

doi:10.1136/gut.32.8.913

Cited by 466 publications

(234 citation statements)

References 46 publications

(10 reference statements)

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“…Caco2-BBE Cells Overexpressing PHB PHB expression is decreased in IBD patients as well as animal models of colitis (Hsieh et al, 2006;Yeo et al, 2006;Theiss et al, 2007a), whereas TNF-␣ is concomitantly increased (Murch et al, 1991;Braegger et al, 1992). We have shown that TNF-␣ not only decreases PHB promoter activation, but that NF-B is essential for this inhibition (Figure 3).…”

Section: Nf-b Nuclear Translocation Nf-b/dna Binding and Nf-b-mediamentioning

confidence: 91%

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Prohibitin Inhibits Tumor Necrosis Factor alpha–induced Nuclear Factor-kappa B Nuclear Translocation via the Novel Mechanism of Decreasing Importin α3 Expression

Theiss

Jenkins

Okoro

et al. 2009

MBoC

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Section: Nf-b Nuclear Translocation Nf-b/dna Binding and Nf-b-mediamentioning

confidence: 91%

“…The concentration of TNF-␣ is increased in serum and stool of IBD patients (Murch et al, 1991;Braegger et al, 1992). The increased level of TNF-␣ potentiates the production of other proinflammatory cytokines, further promoting the inflammatory process.…”

Section: Introductionmentioning

confidence: 99%

Prohibitin Inhibits Tumor Necrosis Factor alpha–induced Nuclear Factor-kappa B Nuclear Translocation via the Novel Mechanism of Decreasing Importin α3 Expression

Theiss

Jenkins

Okoro

et al. 2009

MBoC

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“…In ulcerative colitis in humans, serum and faecal TNFa levels are increased in active disease. 3,4 In the cotton-top tamarin, in which a spontaneous illness closely resembling human ulcerative colitis frequently develops in captivity, animals treated with CDP571, an antibody to TNFa, gained weight, showed a reduction in disease activity and had reproducible improvements in histology scoring. 5 In steroid-unresponsive Crohn's disease complete SUMMARY Background: Tumour Necrosis Factor-alpha (TNFa) is a pro-in¯ammatory cytokine whose expression is increased in the colonic mucosa of patients with active ulcerative colitis.…”

Section: Introductionmentioning

confidence: 99%

Treatment of ulcerative colitis with an engineered human anti‐TNFα antibody CDP571

Evans

Clarke

Heath

et al. 1997

Aliment Pharmacol Ther

130

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Background:Tumour Necrosis Factor‐alpha (TNFα) is a pro‐inflammatory cytokine whose expression is increased in the colonic mucosa of patients with active ulcerative colitis. TNFα antibodies have been shown to be beneficial in animal models of bowel inflammation and in Crohn's disease but have not previously been studied in ulcerative colitis.Methods:Patients with mild/moderate ulcerative colitis were treated openly with a single intravenous infusion of 5 mg/kg of an engineered human IgGγ4 antibody CDP571 and monitored for 8 weeks.Results:Fifteen patients entered the study, eight males and seven females, with a mean age of 44 years. Eleven had left‐sided disease, four extensive disease and six patients were steroid‐unresponsive. The treatment was well tolerated and plasma half‐life of CDP571 was ≈7 days. There was a significant reduction from 6.7 to 4.6 (P = 0.023) in the mean Powell–Tuck score by 1 week post‐infusion and a reduction to 5.5 was seen at 2 weeks (P = 0.218). Significant but modest reductions also occurred in erythrocyte sedimentation rate and serum C reactive protein in the first 2 weeks. Mean Interleukin‐6 plasma concentrations fell from 6.9 to 5.4 pg/mL by week 1, and to 6.1 pg/mL by week 2 (NS). Reductions in sigmoidoscopic score and number of liquid stools were noted but failed to reach statistical significance.Conclusion:A consistent improvement in disease activity was seen in the initial 2 weeks after infusion and the treatment was well tolerated. These promising results support the testing of CDP571 in a larger controlled trial.

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“…TNF-a is widely held as a key pathogenic factor for colitis pathogenesis in the clinic and experimental models. 47 Anti-C5a attenuates intestinal damage G Chen et al accounts for the therapeutic effects of anti-C5a. Strikingly, our results showed that anti-C5a treatment led to upregulation of IL-10 and TGF-b production in colons, indicating that the efficacy of anti-C5a therapy is also ascribed to enhanced immunomodulatory function of IL-10 and TGF-b.…”

Section: F4/80mentioning

confidence: 99%

Blockade of complement activation product C5a activity using specific antibody attenuates intestinal damage in trinitrobenzene sulfonic acid induced model of colitis

Chen¹,

Yang

Gao

et al. 2011

Laboratory Investigation

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Complement represents a chief component of innate immunity in host defense. However, excessive complement activation has been involved in the pathogenesis of inflammatory diseases. In this study, we investigated the contribution of complement to intestinal pathology of patients and rodents with inflammatory bowel disease. The expression of complement effectors (C3a and C3) was increased remarkably in inflamed colons of IBD patients compared with those of normal counterparts. In accordance with this, the sustained activation of complement in serum and colon (including elevated C3a and C5a levels, enhanced hemolytic activity, downregulated expression of C5a receptors) was observed, following the establishment of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, which peaked at 24 h. Mice pretreated with neutralizing anti-C5a antibodies (À2, 0, and 2 days after TNBS instillation) had significantly reduced weight loss and improved macroscopic/microscopic scores, comparable to the efficacy of prednisolone treatment. Strikingly, treatment with anti-C5a at 24 h after TNBS instillation showed remarkable therapeutic effects, whereas prednisolone did not. The efficacy of anti-C5a administration was associated with decreased release of proinflammatory chemokines and cytokines, inhibition of infiltration of neutrophils into colons, and enhanced Th2 response. These findings suggest a disease-promoting role of complement, particular C5a, in the pathology of TNBS-induced colitis in mice, indicating possible therapeutic potentials for C5a-specific antibody in IBD. The inflammatory bowel diseases (IBDs) encompassing Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of gastrointestinal tract, characterized by dysfunction of mucosal T cells, abnormal cytokine production, cellular inflammation, and ultimately damage to the intestinal lining. 1 Although the etiology of IBD remains unknown, there is circumstantial evidence to link IBD to the mucosal immune system's failure to attenuate immunity to endogenous antigen. 1 In recent years, several animal IBD models have been developed. 2,3 Although the relationship of many of these models to human disease is imperfect, the hapten-induced model of colonic inflammation in which 2,4,6-trinitrobenzene sulfonic acid (TNBS) is delivered intrarectally to BALB/c mice displays human CD-like features, notably predominantly IL-12-driving Th1 activity of the mucosal CD4 þ T-cell population and transmural mononuclear inflammation. 3 More recently, a pathogenic role of IL-23, the cytokine sharing p40 subunits with IL-12, has been evidenced in the development of CD. 4 Deficiency of IL-23-specific subunits (p19) leads to failure of colitis induction in a T-cell transfer model. This effect is attributed to suppression of IL-17 production and Th17 differentiation in the colons. 5 The factors that initiate intestinal pathology of CD and elicit Th1/Th17 immune reaction, however, are still

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Serum concentrations of tumour necrosis factor alpha in childhood chronic inflammatory bowel disease.

Abstract: Serum tumour necrosis factor a (TNFa) concentrations were measured by enzyme linked immunoadsorbent assay in 31 normal children and during 65 episodes of clinical remission and 54 episodes of relapse in 92 children with

Cited by 466 publications

References 46 publications

Prohibitin Inhibits Tumor Necrosis Factor alpha–induced Nuclear Factor-kappa B Nuclear Translocation via the Novel Mechanism of Decreasing Importin α3 Expression

Prohibitin Inhibits Tumor Necrosis Factor alpha–induced Nuclear Factor-kappa B Nuclear Translocation via the Novel Mechanism of Decreasing Importin α3 Expression

Treatment of ulcerative colitis with an engineered human anti‐TNFα antibody CDP571

Blockade of complement activation product C5a activity using specific antibody attenuates intestinal damage in trinitrobenzene sulfonic acid induced model of colitis

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