R. Morera

Oral butyrate for mildly to moderately active Crohn's disease

Background : Butyrate exerts anti‐inflammatory effects in experimental colitis and on Crohns disease lamina propria mononuclear cells in vitro.

Increased Enterocyte Apoptosis in Inflamed Areas of Crohn’s Disease

AbstractPURPOSE: Because increased enterocyte apoptosis has been associated with the pathogenesis of several chronic inflammatory diseases, the aim of our study was to investigate epithelial cell death in Crohn’s disease and the possible role of the Fas-Fas ligand system, E-cadherin, and matrix metalloproteinase-1 in modulating enterocyte apoptosis in this condition. METHODS: Endoscopic ileal and colonic biopsy specimens were collected from macroscopically involved and uninvolved areas of 20 patients with Crohn’s disease and 20 subjects who proved to have functional diarrhea. Diagnosis was established by clinical and pathologic criteria. Biopsy specimens were processed for traditional histology and for the immunohistochemical evaluation of Fas, Fas ligand, E-cadherin, Ki67 antigen, and matrix metalloproteinase-1 expression. For the in situ detection of apoptotic cells, terminal deoxynucleotidyl transferase–mediated digoxigenin-deoxyuridine triphosphate nick end labeling was used. RESULTS: The percentages of apoptotic enterocytes were higher in involved than in uninvolved areas of Crohn’s disease patients and normal intestine. No significant difference was found between Crohn’s disease uninvolved areas and normal intestine. In Crohn’s disease, both enterocyte Fas and lamina propria mononuclear cell Fas ligand expression did not differ from controls. E-cadherin was strongly expressed by epithelium in both normal and inflamed intestine, except for the regenerative epithelium over the base of the ulcers, where a reduced E-cadherin expression was observed. The number of Ki67-positive proliferating epithelial cells did not differ either in involved or uninvolved areas of Crohn’s disease patients compared with controls. A lamina propria overexpression of matrix metalloproteinase-1 was found in involved compared with uninvolved Crohn’s disease areas and normal tissue, and a significant positive correlation between matrix metalloproteinase-1 expression and enterocyte apoptosis was found in Crohn’s disease inflamed areas. CONCLUSIONS: Enterocyte apoptosis is increased in involved areas of Crohn’s disease. This increase is not mediated by a Fas-Fas ligand mechanism or by an abnormal E-cadherin distribution. Increased matrix metalloproteinase-1 release from lamina propria mononuclear cells might be one of the possible mechanisms responsible for the increased enterocyte apoptosis in Crohn’s disease.

Depletion of immunoglobulin M memory B cells is associated with splenic hypofunction in inflammatory bowel disease.

OBJECTIVES:IgM memory B cells that are responsible for the protection against infections by encapsulated bacteria, require the spleen for their generation and/or survival. Since the association between inflammatory bowel disease and functional hyposplenism is well described, our aim was to verify whether IgM memory B cells mirror the reduced splenic function in Crohns disease and ulcerative colitis patients.METHODS:Peripheral blood samples were obtained from 32 Crohns disease and 29 ulcerative colitis patients, 33 healthy controls, and 27 splenectomized patients. Perendoscopic intestinal biopsies were also collected from 15 of 32 Crohns disease patients, 14 of 29 ulcerative colitis patients and 13 of 33 control subjects. Counting of erythrocytes with membrane abnormalities (pitted red cells) was used as an indicator of splenic function and flow cytometry was performed to analyze both peripheral and mucosal B cells.RESULTS:Twelve of 32 Crohns disease patients and 13 of 29 ulcerative colitis patients had pitted red cell values >4% and were considered to be hyposplenic. In inflammatory bowel disease patients circulating IgM memory B cells were significantly lower than in control subjects. We observed a significant inverse correlation between the frequency of circulating IgM memory B cell and the pitted red cell values in inflammatory bowel disease patients with hyposplenism. To exclude the possibility that the reduction of circulating IgM memory B cells reflected their recruitment in the inflamed bowel mucosa, lamina propria B-cell populations were also characterized. We found that the frequency of IgM memory B cells was similar in the blood and in the lamina propria of the same patient.CONCLUSIONS:Our findings show that peripheral IgM memory B cells are reduced in inflammatory bowel disease patients and this defect seems to be related to the impairment of splenic function.