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Notes: The administration of indometacin to rats increases intestinal permeability and induces inflammatory pathology of the small bowel. This represents a potential model for Crohn’s disease.〈section xml:id="abs1-2"〉〈title type="main"〉Aims:To analyse the pathogenic role of T cells, tumour necrosis factor and bacterial flora in indometacin-induced changes in small bowel permeability and inflammation.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Rats were given indometacin, 13 mg/kg, on day 1 and day 2. The effects of antibiotic (metronidazole, aztreonam and amoxicillin/clavulanic acid), anti- tumour necrosis factor and interleukin-10 therapy were evaluated. The parameters used were weight change, serum haemoglobin, chromium-51 ethylenediaminetetra-acetate permeability and macro-and microscopic score on day 5. Results in conventionally harboured rats were compared with those in T-cell-free rats. Additional in vitro experiments were carried out to test the effect of metronidazole on tumour necrosis factor production.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Indometacin administration resulted in small bowel ulcers and inflammation, independently of T cells. Metronidazole was more potent than amoxicillin/clavulanic acid and anti-tumour necrosis factor in improving the indometacin-induced small bowel inflammation. Only part of the efficacy was through improvement of increased intestinal permeability. Aztreonam and interleukin-10 had no effect. Metronidazole also suppressed in vitro lipopolysaccharide-induced tumour necrosis factor production, suggesting a therapeutic effect of this drug through the inhibition of tumour necrosis factor.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:These data implicate anaerobic bacteria and tumour necrosis factor production, but not T cells, as essential elements of the pathogenesis of indometacin-induced small bowel inflammation. Tumour necrosis factor is also involved in the change in intestinal permeability. Metronidazole was the most efficacious drug in this model, probably because it suppressed anaerobic bacteria and directly inhibited tumour necrosis factor production.

Notes: Long-term acid suppression is believed to accelerate atrophic gastritis in Helicobacter pylori-positive patients. The influence of long-term therapy with lansoprazole has not been examined.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To study the clinical and endoscopic efficacy and histological evolution of gastric mucosa during 5 years of maintenance treatment with lansoprazole, 30 mg.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Seventy-eight patients with endoscopically proven oesophagitis were followed for 5 years. Biopsies taken at the start of the study, during follow-up and after 5 years were available for 73 patients.〈section xml:id="abs1-4"〉〈title type="main"〉Results:The total endoscopic relapse rate was 14.1%. At the start of the study, 34 patients were Helicobacter pylori negative and 39 were Helicobacter pylori positive (two atrophy, 25 antral gastritis, 12 pangastritis). At 5 years, no histological changes had occurred in Helicobacter pylori-negative patients. In the Helicobacter pylori-positive group, 20 patients developed pangastritis, six had normal histology and one had antral gastritis. Ten of the 12 patients with pangastritis had reduced antral activity. There was no increase in intestinal metaplasia, but there was a tendency towards regression of atrophy in the antrum and towards increased atrophy in the body of the stomach.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:Maintenance treatment with lansoprazole, 30 mg, is efficacious. The development of glandular atrophy and intestinal metaplasia was not accelerated in Helicobacter pylori-positive patients. Helicobacter pylori eradication must be considered only because of the higher cancer risk associated with chronic Helicobacter pylori-related gastritis.

Notes: Anti-TNFα therapy with infliximab is effective for Crohn’s disease. Infliximab neutralizes the biological activities of TNFα, a cytokine involved in host-defence against certain infections.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To evaluate the effects of infliximab on the gut and peripheral immune system functions.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Biopsies and blood samples from three clinical trials of infliximab in Crohn’s disease were analysed. Pharmacokinetics, changes in leucocyte counts and T cell subsets, T cell function, and cytokine profiles of lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (PBMC) were analysed.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Infliximab has a serum half-life of 9.5 days and is still detectable in serum 8 weeks after infusion. Leucocyte counts showed consistent changes from baseline toward normal values after therapy. Monocytes and lymphocytes were modestly increased, while neutrophils were decreased 4 weeks after treatment. Lymphocyte subsets and T cell proliferative responses were not altered after therapy. The proportion of PBMCs capable of producing IFNγ and TNFα did not change, while Th1 cytokine production by stimulated LPMC was decreased after infliximab therapy.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusion:The clinical efficacy of infliximab is based on local anti-inflammatory and immunomodulatory effects in the bowel mucosa, without generalized suppression of systemic immune functions in Crohn’s disease patients.