Increased production of tumour necrosis factor-alpha interleukin-1 beta, and interleukin-6 by morphologically normal intestinal biopsies from patients with Crohn's disease.

Reimund, Jean‐Marie; Wittersheim, Christian; Dumont, Serge; Muller, Christian D.; Kenney, J S; Baumann, René; Poindron, Philippe; Duclos, Bernard

doi:10.1136/gut.39.5.684

Cited by 274 publications

(215 citation statements)

References 27 publications

(3 reference statements)

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“…These cytokines have previously been shown to be increased in media derived from organ cultures of colon tissues from patients with active IBD (23)(24)(25). This provides an additional validation of the use of organ culture methods used here to study the effects of experimental bromelain treatment on cytokine secretion.…”

Section: Discussionsupporting

confidence: 60%

Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro

Onken

Greer

Calingaert

et al. 2008

Clinical Immunology

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Oral bromelain has been anecdotally reported to decrease inflammation in ulcerative colitis (UC). Proteolytically active bromelain is known to decrease expression of mRNAs encoding proinflammatory cytokines by human leukocytes in vitro. To assess the effect of bromelain on mucosal secretion of cytokines in inflammatory bowel disease (IBD), endoscopic colon biopsies from patients with UC, Crohn's disease (CD), and non-IBD controls were treated in vitro with bromelain or media, then cultured. Secretion of pro-inflammatory cytokines and chemokines was measured. Significant increases in granulocyte colony stimulating factor (G-CSF), interferon (IFN)-γ, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) were detected in the media from actively inflamed areas in UC and CD as compared with non-inflamed IBD tissue and non-IBD controls. In vitro bromelain treatment decreased secretion of G-CSF, granulocyte-macrophage colony stimulating factor (GM-CSF), IFN-γ, CCL4/macrophage inhibitory protein (MIP)-1β, and TNF by inflamed tissue in IBD. Bromelain may be a novel therapy for IBD.

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Section: Discussionsupporting

confidence: 60%

Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro

Onken

Greer

Calingaert

et al. 2008

Clinical Immunology

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“…Those cytokines, especially TNF␣, have also been implicated in the pathogenesis of Crohn's disease. 19 Lymphocytic impairment could also result from their being part of the abnormal dysplastic clone, but this probably occurs in only a small minority of MDS. On the other hand, a primary lymphocytic defect could participate in the emergence of clonal myeloid cells.…”

Section: Discussionmentioning

confidence: 99%

Association between myelodysplastic syndromes and inflammatory bowel diseases. Report of seven new cases and review of the literature

et al. 1997

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We report seven patients with both myelodysplastic syndrome (MDS) and inflammatory bowel disease (IBD): Crohn's disease in six cases, ulcerative colitis in one case. We describe their characteristics, and those of 10 previously published similar cases are presented here. Median age at diagnosis of IBD (61 years) was high, as compared to the usual age at diagnosis of IBD. IBD was diagnosed first in nine cases, MDS first in one patient, and both diseases were diagnosed simultaneously in seven cases. Concerning IBD, there was a strong predominance of Crohn's disease (15/17 cases), with an unusually high frequency of colonic involvement (11/15 cases). MDS, in 12/17 cases, showed no excess of marrow blasts. Cytogenetic analysis was abnormal in five of the 13 evaluable cases. These observations suggest that the association between MDS and IBD may not be fortuitous in some cases, and that, in particular, patients with IBD and anemia of nonobvious origin should be evaluated for MDS. The pathogenesis of those associations, however, remains unclear.

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“…Interestingly, the activity of all members of the death receptor family has been correlated positively with disease activity in IBD (40)(41)(42). The precise role of FADD in CD is unknown yet but, in our opinion, warrants further research.…”

Section: Discussionmentioning

confidence: 99%

Hydroxylase Inhibition Abrogates TNF-α–Induced Intestinal Epithelial Damage by Hypoxia-Inducible Factor-1–Dependent Repression of FADD

Hindryckx

Vos

Jacques

et al. 2010

The Journal of Immunology

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Hydroxylase inhibitors stabilize hypoxia-inducible factor-1 (HIF-1), which has barrier-protective activity in the gut. Because the inflammatory cytokine TNF-α contributes to inflammatory bowel disease in part by compromising intestinal epithelial barrier integrity, hydroxylase inhibition may have beneficial effects in TNF-α–induced intestinal epithelial damage. The hydroxylase inhibitor dimethyloxalylglycin (DMOG) was tested in a murine model of TNF-α–driven chronic terminal ileitis. DMOG-treated mice experienced clinical benefit and showed clear attenuation of chronic intestinal inflammation compared with that of vehicle-treated littermates. Additional in vivo and in vitro experiments revealed that DMOG rapidly restored terminal ileal barrier function, at least in part through prevention of TNF-α–induced intestinal epithelial cell apoptosis. Subsequent transcriptional studies indicated that DMOG repressed Fas-associated death domain protein (FADD), a critical adaptor molecule in TNFR-1-mediated apoptosis, in an HIF-1α–dependent manner. Loss of this FADD repression by HIF-1α-targeting small interfering RNA significantly diminished the antiapoptotic action of DMOG. Additional molecular studies led to the discovery of a previously unappreciated HIF-1 binding site in the FADD promoter, which controls repression of FADD during hypoxia. As such, the results reported in this study allowed the identification of an innate mechanism that protects intestinal epithelial cells during (inflammatory) hypoxia, by direct modulation of death receptor signaling. Hydroxylase inhibition could represent a promising alternative treatment strategy for hypoxic inflammatory diseases, including inflammatory bowel disease.

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Increased production of tumour necrosis factor-alpha interleukin-1 beta, and interleukin-6 by morphologically normal intestinal biopsies from patients with Crohn's disease.

Abstract: Background-Increasing evidence points to a important role for inflammatory cytokines for the pathogenesis of Crohn's disease. Aim-To compare the secretion rate of tumour necrosis factor-a (TNF-a), interleukin-1 (IL-1 0) and interleukin-6

Cited by 274 publications

References 27 publications

Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro

Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro

Association between myelodysplastic syndromes and inflammatory bowel diseases. Report of seven new cases and review of the literature

Hydroxylase Inhibition Abrogates TNF-α–Induced Intestinal Epithelial Damage by Hypoxia-Inducible Factor-1–Dependent Repression of FADD

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