Dose-effect of interleukin-10 and its immunoregulatory role in Crohn's disease.

BACKGROUND: Interleukin-10 (IL-10) is currently being extensively studied in clinical trials for the treatment of Crohn's disease (CD). Only marginal effects have, however, been reported, and the dose-response curve was bell-shaped contrasting with the reported data from in vitro experiments. AIM: To use another in vitro model to analyze the effect of rhIL-10 and rhIL-4 on the spontaneous mucosal TNF-alpha secretion in patients with CD, and to characterize the phenotype of the cells targeted by rhIL-10. METHODS: Non-inflamed colon biopsies from CD patients were cultured for 16 hours in presence of different concentrations of rhIL-10 or rhIL-4. The numbers of TNF-alpha-secreting cells among isolated lamina propria mononuclear cells (LPMNC) were estimated by Elispot. RESULTS: Both rhIL-10 and rhIL-4 down-regulate TNF-alpha secretion by LPMNC from CD patients, with a more pronounced effect with rhIL-10. These effects were closely linked to the cytokine concentrations used, with a bell-shaped dose-response curve. Residual TNF-alpha secretion, in the presence of optimal rhIL-10 concentration was mainly attributable to CD3+ T cells. In contrast, at higher rhIL-10 concentrations, CD3- cells contributed significantly to the TNF-alpha secretion. CONCLUSIONS: The in vitro model we used, demonstrates that IL-4, but mostly IL-10, efficiently suppresses TNF-alpha secretion in LPMNC from CD patients, with a dose-response curve similar to results obtained in vivo. Resistance at high rhIL-10 concentrations was associated with a change in the phenotype of TNF-alpha-secreting cells.

Predictive factors of positive findings in patients explored by push enteroscopy for unexplained GI bleeding.

BACKGROUND: The diagnostic yield of push enteroscopy (PE) in patients with unexplained overt GI bleeding is about 30%. The aim of this study was to assess for predictive factors of positive findings. METHODS: A total of 182 patients referred to two endoscopic centers (European Georges Pompidou Hospital [Paris, France] and Erasmus Hospital [Brussels, Belgium]) for unexplained overt GI bleeding (melena [57%], hematochezia [26%], or hematochezia associated with melena [17%]) were included in this retrospective study. Predictive factors associated with positive findings at upper PE were studied by using uni- and multivariate analysis. RESULTS: The overall diagnostic yield of upper PE was 34% (62/182), but lesions were found beyond the second duodenum in 25% of the patients (45/182). Factors significantly associated with positive findings at upper PE were the following. (1) In univariate analysis: the presence of melena, Hb level <7 g/dL, blood transfusion >4 units per patient, chronic renal failure, disorder of hemostasis or effective anticoagulant treatment, history of intestinal arteriovenous malformation, and age > 65 years. (2) In multivariate analysis: chronic renal failure and presence of melena. If only jejunal lesions were considered, chronic renal failure was the only predictive factor associated with positive findings at upper PE in multivariate analysis. The severity of GI bleeding did not reach statistical significance ( p = 0.06). Delay between GI bleeding and PE, number of previous standard endoscopies and previous episodes of bleeding were not associated with positive findings in upper PE. CONCLUSIONS: In patients with unexplained overt GI bleeding, upper PE has a higher diagnostic yield in patients with chronic renal failure and patients with melena (vs. hematochezia).

A prospective comparative study of push and wireless-capsule enteroscopy in patients with obscure digestive bleeding.

OBJECTIVES: To prospectively compare the global and specific diagnostic yields of push and wireless videocapsule enteroscopy for small bowel lesions in patients with obscure digestive bleeding after esogastroduodenoscopy and colonoscopy. METHODS: The patients studied had unexplained chronic iron-deficient anemia or digestive blood loss after routine investigations. Small bowel investigation was performed first with the wireless-capsule (M2A, Given Imaging) and then with the push-enteroscope (Olympus SIF100). RESULTS: Twenty-one patients were included in the protocol (14 females and 7 males), whose mean age was 60 years (range: 18 to 81). All patients had iron-deficient anemia with occult bleeding (n = 16) or overt bleeding (n = 5). A digestive lesion was observed in 14 of 21 cases (66%). Lesions were: esophageal varices (n = 2), reflux esophagitis (n = 1), upper gastrointestinal tract ulcerations (n = 9), intestinal angioectasia (n = 4), ileal varices (n = 1), cecal angioectasia (n = 1) and tumor-like angioma in the jejunum (n = 1). These 19 lesions were discovered by both methods in 10 cases (52%), by push-enteroscopy only in 6 (31%) and by wireless-capsule endoscopy only in 3 (17%). The global diagnostic yield was therefore slightly but not significantly higher for push wireless-capsule enteroscopy (61 vs 52%; NS) and the specific diagnostic yield was similar (20%). Interobserver agreement on the wireless-capsule recordings reached 85% for detection of findings. CONCLUSIONS: In patients with obscure digestive bleeding, no significant difference in diagnostic yield was evidenced between push and wireless-capsule endoscopy. The main advantage of the latter method versus the former was the detection of distal lesions in the small bowel. Wireless-capsule enteroscopy is mandatory for patients with active unexplained bleeding and negative push-enteroscopy, or for defining the extension of a disease involving, for instance, the presence of angioectasia.

Budesonide in collagenous colitis: a double-blind placebo-controlled trial with histologic follow-up.

BACKGROUND & AIMS: Collagenous colitis (CC) is a well-described entity causing chronic diarrhea and characteristic histologic findings. Several treatment options have been suggested, but no controlled data are available. We conducted a placebo-controlled trial to show the clinical and histologic effects of budesonide in CC. METHODS: Twenty-eight patients were randomly assigned to receive placebo (n = 14) or budesonide 9 mg daily (n = 14) for 8 weeks. Patients were evaluated clinically, and blinded biopsy specimens were analyzed from fixed locations at weeks 0 and 8. Clinical response was defined as a decrease of at least 50% in the disease activity score (number of bowel movements in the last 7 days). At week 8, nonresponders received open-label budesonide for the next 8-week period; responders discontinued treatment and were followed up. RESULTS: Three patients discontinued the study prematurely. Intention-to-treat analysis showed clinical response in 8 of 14 patients in the budesonide group compared with 3 of 14 responders for placebo (P = 0.05) after 8 weeks of blinded therapy, together with improved stool consistency. Histologically, there was no change in the mean thickness of the collagen band but a significant decrease of the lamina propria infiltrate in the budesonide group (P < 0.001). CONCLUSIONS: Budesonide is efficacious in inducing short-term clinical response in CC with significant reduction of the histologic infiltrate in the lamina propria.