[Inflammatory bowel disease in three elderly patients; an unexpected diagnosis in long-standing abdominal complaints]. / Inflammatoire darmziekten bij 3 oudere patiënten; een onverwachte diagnose bij langer bestaande abdominale klachten.

Three female patients, 68, 75 and 68 years of age, were treated symptomatically for long-standing abdominal complaints such as gastralgia, diarrhoea and loss of blood or mucus with the stools. In all cases there was no clear diagnosis and treatment did not relieve the complaints, even after surgery. Inflammatory bowel disease was ultimately established on the basis of histological analysis of both resection specimens and biopsies in combination with endoscopy. Clinical improvement was achieved after adequate treatment. Aspecific abdominal complaints in elderly patients have multiple differential diagnoses. The most important of these are diverticulitis, ischaemia and colon carcinoma. In contrast, inflammatory bowel disease (both Crohn's disease and ulcerative colitis) is usually diagnosed at a younger age. Ignoring inflammatory bowel disease as a cause of abdominal complaints in elderly patients could be responsible for inadequate treatment, higher morbidity and an increase of symptoms.

The dynamics of gastritis.

The dynamics of gastritis remain a topic of intense investigation. The results of these investigations have increased our knowledge concerning the development of preneoplastic lesions and cancer of the stomach and given us insight with regard to the interactions among bacterial colonization, chronic inflammation, and carcinogenesis in other organs. The past year has presented us with further data showing that the progression of chronic gastritis to gland loss and gastric cancer is related to the severity of inflammation, which is influenced by the characteristics of the bacterial strain, host genetics, and hypochlorhydria. In contrast, Helicobacter pylori eradication leads to a rapid disappearance of neutrophils in the gastric mucosa. Chronic inflammation with mononuclear cells also improves upon eradication, but at a much slower rate, usually not leading to normalization within the first year after therapy. Whether H. pylori eradication can thus prevent new development of atrophy and metaplasia as well, or lead to regression of pre-existing lesions, has been the topic of many studies by now. Unfortunately, most of these studies have suffered from their case design, limited sample size, and short follow-up. Therefore, the conflict in outcome of these case studies comes as no surprise. The few prospective, randomized, controlled studies, however, strongly confirm that H. pylori eradication leads to healing of gastritis, which can at least halt further development of atrophy and metaplasia. Whether these lesions can truly regress remains to be proven.

Variation in gut-homing CD27-negative lymphocytes in inflammatory colon disease.

Prolonged antigenic stimulation results in lymphocyte shedding of CD27, a member of the tumour necrosis factor receptor (TNFR) family, and transformation to a stable phenotype capable of synthesizing interleukin-4 (IL-4). Co-expression of alpha4beta7 identifies those cells with gut-homing potential. We have investigated these cell populations in patients with inflammatory colonic disease. Circulating and lamina propria mononuclear cells were isolated from patients with Crohn's disease (CD), ulcerative colitis (UC), non-inflammatory bowel disease (non-IBD) colonic inflammation and healthy controls. Double and triple colour flow cytometry for CD3, CD4, CD27, alpha4beta7 and intracellular cytokines was performed. Circulating CD4+ CD27- populations were increased in patients with CD (8.8 +/- 0.8%, P < 0.001), UC (12.2 +/- 1.9%, P < 0.001) and non-IBD colitis (10.5 +/- 1.3%, P < 0.01) as compared with controls (6.1 +/- 0.5%). CD4+ CD27- alpha4beta7+ cells were increased in CD (P < 0.01). Lamina propria CD4+ CD27- populations were depressed significantly in CD (P < 0.05), UC (P < 0.02) and non-IBD colitis (P < 0.03). Mucosal CD4+ CD27- cells synthesized IL-4 in preference to interferon-gamma. Thus, colonic inflammation is associated with alterations in gut-tropic circulating and mucosal populations of differentiated memory T cells with the phenotype of predominantly IL-4-synthesizing cells.

Anti-inflammatory effect of interleukin-10 in rabbit immune complex-induced colitis.

BACKGROUND: Interleukin-10 (IL-10) is an anti-inflammatory cytokine that downregulates the secretion of pro-inflammatory cytokines and additionally induces the secretion of anti-inflammatory cytokines, thus possibly leading to reduction of chronic inflammation in inflammatory bowel disease. In this study we evaluated the anti-inflammatory effect of IL-10 in a model of acute colitis in rabbits. METHODS: Colitis was induced by rectal instillation of formalin, 0.65%, followed by intravenous infusion of 0.85 ml heat-aggregated rabbit immunoglobulin. Rabbits were treated with an intravenous bolus of recombinant human IL-10 (SCH52000), 100 microg/kg (n=14) or 500 microg/kg (n=14), 1 h before induction of colitis (control group, n=12). RESULTS: High-dose IL-10 improved macroscopic scores of inflammation and decreased tissue myeloperoxidase levels and leukotriene B4 levels in dialysate fluid. Thromboxane B2 and prostaglandin E2 levels remained unaffected. CONCLUSION: IL-10 ameliorates acute colitis in this model. Consequently, this anti-inflammatory cytokine may have a role in the therapy of acute inflammatory bowel disease.

Altered expression of alpha 4 beta 7, a gut homing integrin, by circulating and mucosal T cells in colonic mucosal inflammation.

BACKGROUND AND AIMS: Expression of alpha 4 beta 7 on memory T lymphocytes identifies a cell population that preferentially migrates to the gut. Detection of alpha 4 beta 7 on circulating lymphocytes may permit the identification of specific subsets trafficking between the circulation and the gut in inflammatory bowel diseases. PATIENTS: Samples and clinical details were taken from patients with Crohn's disease (CD), ulcerative colitis (UC), diverticulitis/ infectious colitis, and healthy controls. METHODS: Peripheral blood and lamina propria mononuclear cells were isolated. Cells were labelled with CD3, CD4, CD25, CD45RO or alpha 4 beta 7. RESULTS: Median levels of circulating total memory T cells (CD4+CD45RO+) were increased in CD (p < 0.01) and UC (p < 0.05). However, the proportion of systemic gut homing T cells (CD4+CD45RO+ alpha 4 beta 7+) was decreased in CD (p < 0.05), UC (p < 0.002), and inflammatory controls (p < 0.05). Levels of activated gut homing T cells (CD4+CD25+ alpha 4 beta 7+) were increased in CD (p < 0.01) and UC (p < 0.05). For both CD4+CD45RO+ and CD4+CD25+ cells, the proportion of lymphocytes coexpressing alpha 4 beta 7 was decreased compared with controls. In small and large intestine lamina propria, expression of alpha 4 beta 7+ on CD3+ cells was extensive, although it was decreased in CD (p < 0.03), UC (p < 0.05), and inflammatory controls (p < 0.05). CONCLUSIONS: Circulating and mucosal gut homing lymphocyte populations are changed in patients with colonic inflammation. This may arise due to a dilution effect from recruited naive T cells, or from integrin down regulation. Changes in general CD4+ lymphocyte populations mask more subtle variations in those cells with gut homing potential.

Lexipafant (BB-882), a platelet activating factor receptor antagonist, ameliorates mucosal inflammation in an animal model of colitis.

OBJECTIVE: To assess the anti-inflammatory action of lexipafant (BB-882), a platelet activating factor antagonist, in an animal model of acute colitis. DESIGN: An animal intervention study. METHODS: Following the rectal instillation of formalin 0.75% into male New Zealand White (NZW) rabbits, 0.85 ml of aggregated immunoglobulin was administered i.v. Treatment groups (0.8 mg/kg, n = 6; 2.4 mg/kg, n = 13; 3.2 mg/kg, n = 10) were given bolus doses of BB-882 two-hourly i.v. (control group, n = 25). Rectal dialysis was performed before induction of colitis and sacrifice. Dialysate leukotriene B4 (LTB4), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) levels were determined. Tissue was saved for histology and measurement of myeloperoxidase content. RESULTS: There was a dose-dependent improvement in macroscopic scores (2.4 and 3.2 mg/kg: P < 0.02, P < 0.001) and myeloperoxidase levels (3.2 mg/kg: P < 0.04). Dialysate LTB4 levels fell (2.4 and 3.2 mg/kg: P < 0.03, P < 0.02) as did PGE2 levels. TXB2 concentrations remained unaffected. CONCLUSION: The PAF receptor antagonist BB-882 shows efficacy in treating inflammation in an animal model of acute colitis as evidenced by a dose-dependent fall in macroscopic mucosal damage, neutrophil infiltration and reduced generation of inflammatory mediators.