Inflammatory bowel disease mucosal biopsies have specialized lymphokine mRNA profiles

Mullin, Gerard E.; Maycon, Zev R.; Braun-Elwert, Lorenz; Cerchia, R; James, Stephen P.; Katz, Seymour; Weissman, Gary S.; McKinley, Matthew; Fisher, Stanley E.

doi:10.1002/ibd.3780020105

Cited by 32 publications

(7 citation statements)

References 46 publications

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“…Some IBD patients have a decreased mucosal IL-4 production [26] and in some experimental colitis models, such as in IL-2 knockout mice [27], IL-4 production is down-regulated. In contrast to CD, UC has no such typical Th1 cytokine pattern [23,28]. In DSS-induced colitis, a UC-like model, IL-4 secretion is up-regulated during its chronic phase.…”

Section: Discussionmentioning

confidence: 99%

Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines

Dieleman¹,

Palmen²,

Akol³

et al. 1998

Clinical and Experimental Immunology

948

735

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SUMMARYOral administration of DSS has been reported to induce an acute and chronic colitis in mice. The aim of our study was to evaluate if the chronic phase of DSS-induced colitis was characterized by a Th1/Th2 response and how this would relate to mucosal regeneration. Swiss Webster mice were fed 5% DSS in their drinking water for 7 days, followed by 2-5 weeks consumption of water. Control mice received only water. The animals were killed at 3 and 6 weeks after induction. Their colons were isolated for histology and immunohistochemistry, using specific MoAbs for T and B cells, macrophages, interferon-gamma (IFNg), IL-4 and IL-5. Colons were scored for inflammation, damage and regeneration. Two weeks after stopping DSS the colonic epithelium had only partially healed. Total colitis scores were still increased, especially in the distal colon, which was due to more inflammation, damage and less regeneration. In areas of incomplete colonic healing the basal parts of the lamina propria contained macrophages and CD4 þ T cells. These CD4 þ T cells showed a focal increase of IFN-g and IL-4 staining compared with control animals. These findings were still observed 5 weeks after stopping DSS in some mice, albeit less extensive. Chronic DSS-induced colitis is characterized by focal epithelial regeneration and a Th1 as well as Th2 cytokine profile. We postulate that chronic immune activation mediated by both populations of Th cells can interfere with colonic healing and can play a role in the pathogenesis of chronic colitis.

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Section: Discussionmentioning

confidence: 99%

Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines

Dieleman¹,

Palmen²,

Akol³

et al. 1998

Clinical and Experimental Immunology

948

735

View full text Add to dashboard Cite

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“…Thus, in previous studies conducted by ourselves and others, it has been shown that human UC is associated with elevated IL-5 secretion and normal IFN-␥ secretion; nevertheless, it cannot as yet be called a Th2 inflammation because it is not associated with elevated IL-4 secretion, the usual driving force of Th2 responses. On the other hand, established Crohn's disease is quite definitely a Th1 inflamma-tion since IL-12 and IFN-␥ secretion is elevated and there is no increase in either IL-4 or IL-5 secretion (2)(3)(4)(5)31). On this basis, it seems reasonable to suggest that oxazolone colitis is a murine model related to but not identical to UC, whereas TNBS colitis is a model related to Crohn's disease.…”

Section: Discussionmentioning

confidence: 99%

Oxazolone Colitis: A Murine Model of T Helper Cell Type 2 Colitis Treatable with Antibodies to Interleukin 4

Boirivant

Fuss

Chu

et al. 1998

The Journal of Experimental Medicine

484

365

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In this study we describe oxazolone colitis, a new form of experimental colitis. This model is induced in SJL/J mice by the rectal instillation of the haptenating agent, oxazolone, and is characterized by a rapidly developing colitis confined to the distal half of the colon; it consists of a mixed neutrophil/lymphocyte infiltration limited to the superficial layer of the mucosa which is associated with ulceration. Oxazolone colitis is a T helper cell type 2 (Th2)-mediated process since stimulated T cells from lesional tissue produce markedly increased amounts of interleukin (IL)-4 and IL-5; in addition, anti–IL-4 administration leads to a striking amelioration of disease, whereas anti–IL-12 administration either has no effect or exacerbates disease. Finally, this proinflammatory Th2 cytokine response is counterbalanced by a massive transforming growth factor-β (TGF-β) response which limits both the extent and duration of disease: lesional (distal) T cells manifest a 20–30-fold increase in TGF-β production, whereas nonlesional (proximal) T cells manifest an even greater 40–50-fold increase. In addition, anti–TGF-β administration leads to more severe inflammation which now involves the entire colon. The histologic features and distribution of oxazolone colitis have characteristics that resemble ulcerative colitis (UC) and thus sharply distinguish this model from most other models, which usually resemble Crohn's disease. This feature of oxazolone colitis as well as its cytokine profile have important implications to the pathogenesis and treatment of UC.

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“…In contrast with experimental models of colitis, very few data have been published concerning the mucosal IL-10 levels in patients with Crohn's disease or UC (30)(31)(32). Recently, Autschbach et al have found a relative elevated expression of IL-10 by inflammatory mononuclear cells in IBD that may be not sufficient to control the production of proinflammatory cytokines such as IL-1 (33).…”

Section: Il-8 and Il-i0 In Pouchitismentioning

confidence: 99%

Pouchitis is associated with mucosal imbalance between interleukin-8 and interleukin-10

Bulois¹,

Maunoury²,

Gambiez³

et al. 2007

Inflamm Bowel Dis

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Summary:Background: Mucosal lesions of pouchitis are characterized by a neutrophil infiltrate. Interleukin (1L)-8 is the main mediator involved in neutrophil recruitment and is downregulated by IL-10. Aim: To look for an imbalance between IL-8 and IL-I 0 in patients with pouchitis. Patients/Methods: 18 patients having an ileoanal pouch for ulcerative colitis were studied. Eleven had pouchitis defined by the pouchitis disease activity index of 2 7 points and 7 had no history of pouchitis. Biopsies taken at the site of inflammation or in the normal mucosa were scored for the histologic lesions, the intensity of neutrophil infiltration, and the presence of crypt abscesses. Mucosal IL-8 and IL-10 mRNA were quantified by competitive polymerase chain reaction. Results: IL-8, IL-10, and IL-IOILL-8 mRNA were similar in patients with or without pouchitis. IL-8 mRNA levels were significantly higher in patients with a histologic score >2 (p = 0.01) and in patients with crypt abscesses (p = 0.01). IL-lO/IL-8 mRNA was significantly lower in patients having a histologic score >2 (p = 0.019), a neutrophil infiltration 2 10% (p = 0.013), and crypt abscesses (p = 0.01). Conclusion: Histologic lesions of pouchitis are associated with a mucosal imbalance between IL-8 and &lo. IL-10 could be proposed as a new treatment for pouchitis.

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Inflammatory bowel disease mucosal biopsies have specialized lymphokine mRNA profiles

Cited by 32 publications

References 46 publications

Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines

Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines

Oxazolone Colitis: A Murine Model of T Helper Cell Type 2 Colitis Treatable with Antibodies to Interleukin 4

Pouchitis is associated with mucosal imbalance between interleukin-8 and interleukin-10

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