Steroids reduce local inflammatory mediator secretion and mucosal permeability in collagenous colitis patients.

AIM: To study the effect of oral steroids upon clinical response and rectal mucosa secretion of eosinophil cationic protein (ECP), myeloperoxidase (MPO), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and albumin in patients with collagenous colitis (CC). METHODS: A segmental perfusion technique was used to collect perfusates from rectum of CC patients once before and twice (one and four weeks) after the start of steroid treatment. Clinical data was monitored and ECP, MPO, bFGF, VEGF and albumin concentrations were analyzed by immunochemical methods in perfusates and in serum. RESULTS: Steroids reduced the number of bowel movements by more than five times within one week and all patients reported improved subjective well-being at wk 1 and 4. At the same time, the median concentrations of ECP, bFGF, VEGF and albumin in rectal perfusates decreased significantly. MPO values were above the detection limit in only 3 patients before treatment and in none during treatment. VEGF, bFGF, ECP and albumin concentrations correlated with each other with the exception of ECP and albumin. A decrease of serum ECP and VEGF concentrations was also seen even if the overtime reduction was not significant. CONCLUSION: Oral steroid treatment in CC patients induced a simultaneous reduction of bowel movements and rectal release of ECP, bFGF, VEGF and albumin, suggesting that these polypeptides and increased mucosal permeability are important components of the pathophysiology in collagenous colitis.

Health-related quality of life is impaired in active collagenous colitis.

OBJECTIVES: The characteristic clinical symptoms of collagenous colitis are non-bloody diarrhoea, urgency and abdominal pain. Treatment is aimed at reducing the symptom burden and the disease impact on patients' health-related quality of life. The objective of this study was to analyse health-related quality of life in patients with collagenous colitis. METHODS: In a cross-sectional, postal HRQL survey, 116 patients with collagenous colitis at four Swedish hospitals completed four health-related quality of life questionnaires, two disease-specific (Inflammatory Bowel Disease Questionnaire and Rating Form of IBD Patient Concerns), and two generic (Short Form 36, SF-36, and Psychological General Well-Being, PGWB), and a one-week symptom diary. Demographic and disease-related data were collected. Results for the collagenous colitis population were compared with a background population controlled for age and gender (n = 8931). RESULTS: Compared with a Swedish background population, patients with collagenous colitis scored significantly worse in all Short Form 36 dimensions (p < 0.01), except physical function. Patients with active disease scored worse health-related quality of life than patients in remission. Co-existing disease had an impact on health-related quality of life measured with the generic measures. Lower education level and shorter disease duration were associated with decreased well-being. CONCLUSION: Health-related quality of life was impaired in patients with collagenous colitis compared with a background population. Disease activity is the most important factor associated with impairment of health-related quality of life. Patients in remission have a health-related quality of life similar to a background population.

Accumulation, activation, and survival of neutrophils in ulcerative colitis: regulation by locally produced factors in the colon and impact of steroid treatment.

BACKGROUND AND AIMS: Neutrophil granulocytes infiltrate the intestinal mucosa in active ulcerative colitis (UC), and may contribute to tissue damage and inflammation. The aim of this investigation was to study the importance of locally produced factors and the impact of steroid treatment on neutrophil functions in UC. PATIENTS AND METHODS: Intestinal perfusion fluids from 11 patients with active distal UC before and after seven and 28 days of treatment with prednisolone and from seven control patients were used in the study. Neutrophil migration towards perfusion fluid was measured in a microchemotaxis chamber. The effect of perfusion fluids on neutrophil activation was assessed as the surface expression of CD66b by flow cytometry. Neutrophil survival was evaluated by staining with propidium iodide, annexin V, and fluorescein di-acetate. We also assessed the viability of freshly isolated tissue neutrophils from rectal biopsy samples. RESULTS: Perfusion fluids from untreated patients caused increased migration, activation, and survival of neutrophils. Perfusion fluids collected after treatment had no effect on neutrophil migration, but some of the activation and anti-apoptotic effects remained after 7 days. Anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibited the anti-apoptotic effect of perfusion fluids. Rectal tissue neutrophils from patients with active proctitis had increased viability compared to patients with inactive proctitis and control subjects. CONCLUSIONS: These data show that mediators in the colon of patients with active UC stimulate the migration, activation, and survival of neutrophils. The activities were partly neutralized by topical steroid treatment. We also identified GM-CSF as an anti-apoptotic factor for neutrophils in inflamed colon.

Vascular endothelial growth factor (VEGF)--a possible mediator of inflammation and mucosal permeability in patients with collagenous colitis.

Patients with collagenous colitis have watery diarrhea and histopathologically thickened collagen layer with discrete signs of mucosal inflammation. Vascular endothelial growth factor (VEGF) is a potent angiogenic, mitogenic, permeability, and fibrosis enhancing peptide and it was studied by segmental perfusion and immunohistochemistry in patients and controls. The concentrations of VEGF were significantly increased in perfusates from both the descending colon and the rectum in patients compared to controls but this difference was not found in serum. Immunohistochemical staining showed expression of VEGF within colon epithelial cells, inflammatory cells, and fibroblasts in the lamina propria. The intensity of staining in the surface epithelium was not different between patients and controls but in the lamina propria the intensity was significantly higher among controls. Patients with collagenous colitis have increased colorectal mucosal secretion of VEGF, which may lead to albumin leakage and promote fibrosis with deposition of collagen.

Mucosal secretion and expression of basic fibroblast growth factor in patients with collagenous colitis.

OBJECTIVES: Collagenous colitis (CC), a condition of unknown ethiology and pathophysiology, is characterized by watery diarrhea and increased amounts of collagen in the colonic mucosa. Basic fibroblast growth factor (bFGF) is a potent multifunctional growth factor that stimulates proliferation and differentiation of fibroblasts that was recently detected in high intraluminal concentrations in patients with ulcerative colitis. In this study we examined the secretion and expression of bFGF in the colorectal mucosa of patients with CC. METHODS: Ten CC patients and 10 control patients underwent colonoscope-based segmental perfusion of the descending colon and rectum. The concentrations of bFGF in perfusate and serum were determined by immunochemical methods, and the expression of bFGF was analyzed immunohistochemically in biopsy samples from colonic mucosa. RESULTS: The median concentrations of bFGF in perfusates from the descending colon and rectum were increased 4-fold in CC patients compared with control patients. The median concentration of bFGF in serum was not significantly different in patients and controls. Immunohistochemical staining of bFGF was located in the colorectal epithelial cells and in exsudate on the luminal side of these cells. In the lamina propria, inflammatory cells and fibroblasts contained bFGF. There were no differences in the intensity of bFGF staining in surface epithelium or lamina propria between patients and controls. CONCLUSIONS: Local investigation of the colorectal mucosa seems to be crucial when studying the pathophysiology of CC. Increased colorectal mucosal secretion of bFGF in patients with CC may promote differentiation of fibroblasts and thereby lead to increased subepithelial collagen deposition.

A new method for the quantification of neutrophil and eosinophil cationic proteins in feces: establishment of normal levels and clinical application in patients with inflammatory bowel disease.

OBJECTIVES: The aims of this study were 1) to develop a valid method for the measurement of the eosinophil proteins eosinophil cationic protein (ECP) and eosinophil protein X (EPX) and neutrophil proteins myeloperoxidase and human neutrophil lipocalin (HNL) in feces and 2) to investigate their potential role as disease activity markers in inflammatory bowel disease (IBD). METHODS: Feces samples were obtained from 44 apparently healthy individuals (HIs), 18 patients with IBD (11 with ulcerative colitis [UC] and seven with Crohn's disease [CD]), and three with collagen colitis. The granulocyte markers were measured using immunoassays in supernatants from processed feces. RESULTS: ECP, myeloperoxidase, and, to a lesser degree, EPX and HNL were bound to the solid part of feces. However, feces homogenized in an extraction buffer containing the cationic detergent N-cetyl-N,N,N-trimethylammonium bromide allowed an efficient recovery of the proteins (i.e., up to 100-fold increased levels compared to homogenization in saline). All four proteins were stable for at least 7 days at +6 degrees C and at least 3 days at +22 degrees C. The normal fecal geometric mean (95th percentile) levels of ECP, EPX, myeloperoxidase, and HNL were estimated to be, respectively, 1.69 microg/g (6.41), 0.57 microg/g (1.72), 3.54 microg/g (8.77), and 1.97 microg/g (4.91). Markedly increased feces levels of all markers (p < 0.0002), compared to HIs and CD patients, were observed in UC. However, the marker levels in CD patients were significantly increased relative to HIs (p < 0.05 to p < 0.0002). Increased levels of HNL and myeloperoxidase were also observed in the three collagen colitis patients. The discriminative capability between UC patients and HIs was somewhat superior for EPX and myeloperoxidase. CONCLUSIONS: The method described here takes into account the molecular properties of the granule proteins and the heterogeneity in feces consistency, which is a prerequisite for a valid and reproducible measurement of cationic granule proteins. We suggest that EPX and myeloperoxidase, when applied in IBD, are the best eosinophil and neutrophil markers for studying GI inflammation.