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PubMed1998

Role of interleukin-10 in a murine model of dextran sulfate sodium-induced colitis.

BACKGROUND: Increased production of proinflammatory cytokines is characteristic of both animal models of experimental colitis and human inflammatory bowel disease. This study was designed to characterize the functional role of interleukin (IL)-10 in a murine model of experimental colitis. METHODS: Cytokine profiles were analyzed in animals with dextran sulfate sodium-induced colitis. The effect of treatment with IL-10 or anti-IL-10 antibodies on colonic cytokine production in vitro and tissue damage in vivo were evaluated. RESULTS: After the induction of colitis, there was a time-dependent increase in tissue tumor necrosis factor-alpha and IL-1beta levels, followed by a peak of the IL-10 level. The production of tumor necrosis factor-alpha and IL-1beta by cultured colonic tissues was inhibited by addition of IL-10, and conversely, it was enhanced by anti-IL-10. Treatment with IL-10 resulted in a marked improvement in intestinal inflammation. Blocking endogenous IL-10 was found to cause a modest exacerbation of inflammation. CONCLUSIONS: These results show that IL-10 has a functional role in regulating colonic inflammation during experimental colitis.

Animals↗
PubMed1998

Increased colonic permeability in patients with ulcerative colitis: an in vitro study.

BACKGROUND: Colonic permeability was studied in vitro in patients subjected to colectomy because of ulcerative colitis and in control patients undergoing colonic resections for cancer. METHODS: The mucosal layer from fresh colonic segments was stripped and mounted in Ussing diffusion chambers containing modified Krebs buffer solution. The mucosa to serosa passage of the marker molecules 14C-mannitol and ovalbumin was measured for 120 min. RESULTS: Marker passage was significantly increased in colitis patients compared with control patients, irrespective of age, sex, duration of disease, and treatment. Marker passage was further increased in patients with acute colitis. The increased colonic permeability may be explained by inflammation and the resultant loss of mucosal integrity. The increased permeability to ovalbumin implies that permeability to luminal macromolecules, such as bacterial products and other antigenic substances, might be increased in colitis. CONCLUSIONS: The results suggest a derangement of the colonic barrier, as evidenced by an increased mucosal permeability in both chronic and acute colitis.

Adolescent↗
PubMed1998

Recognition of bactericidal/permeability-increasing protein by perinuclear anti-neutrophil cytoplasmic antibody-positive sera from ulcerative colitis patients: prevalence and clinical significance.

BACKGROUND: The aim of this study was to evaluate a) the role of bactericidal/permeability-increasing protein (BPI) as a possible antigen determining perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) reactivity in ulcerative colitis and b) the prevalence and clinical correlates of anti-BPI antibodies in patients with ulcerative colitis on the basis of their p-ANCA status. METHODS: p-ANCA and anti-BPI antibodies were evaluated by means of indirect immunofluorescence and enzyme-linked immunosorbent assay methods in a group of 112 ulcerative colitis patients (including 42 patients subjected to proctocolectomy) well defined as far as their clinical features and p-ANCA status. RESULTS: Anti-BPI antibodies were detected in 24% of non-operated patients and were significantly more frequent in p-ANCA-positive patients (32% versus 5% in p-ANCA-negative patients; P < 0.015). The prevalence of anti-BPI antibodies was similar in non-operated and operated patients and was high in men, in patients with an extensive and aggressive disease, and in patients developing pouchitis after surgery. CONCLUSIONS: These data indicate that BPI is a neutrophil antigen frequently recognized by p-ANCA-positive ulcerative colitis sera. The presence of anti-BPI antibodies appears to identify further immunologic and clinical heterogeneity in ulcerative colitis.

Adolescent↗
PubMed2001

Enteropathogenic Escherichia coli and ulcerative colitis in cotton-top tamarins (Saguinus oedipus).

The cotton-top tamarin (CTT; Saguinus oedipus) is an endangered New World primate that develops a highly prevalent idiopathic colitis resembling human ulcerative colitis. This study found that enteropathogenic Escherichia coli (EPEC) caused acute colitis in CTTs, which was associated with ulcerative colitis. EPEC clinical isolates revealed localized adherence patterns by HEp-2 assay and were devoid of Shiga-toxin production. Sequencing of the eae gene (GenBank accession no. AF319597) revealed 99.2% identity to sequences of human isolates (GenBank AF116899) and corresponded to the epsilon intimin gene subtype. Detection of intimin sequences by polymerase chain reaction on primary fecal cultures indicated widespread EPEC infection in the CTT colony. Prospective analysis revealed that animals with fecal cultures positive for intimin sequences had a higher frequency of active colitis (75.0% vs. 27.2%; P<.005, chi(2) test) and higher histological scores of colonic inflammation (0.875 vs. 0.455, respectively; P<.05, Mann-Whitney rank sum test).

Adhesins, Bacterial↗
PubMed1988

Does ulcerative colitis behave differently in the elderly?

The clinical course of all new patients with ulcerative colitis or indeterminate colitis aged 65 years or older diagnosed in one health district (population 274,000) between 1 January 1975 and 31 December 1984 has been compared with that of all new patients 55 years or younger diagnosed in the same period. Elderly patients were admitted more often in a first attack and were more likely to receive systemic steroids. No elderly patient required urgent surgery and no patient in either group died of ulcerative colitis or its complications. The mortality amongst elderly patients with ulcerative colitis was no greater than expected in a population of the same age. The prognosis for ulcerative colitis in elderly patients is the same as for younger patients.

Age Factors↗
PubMed2001

Small-area variations and sociodemographic correlates for the incidence of Crohn's disease and ulcerative colitis.

The objectives of this study were to describe variations in the incidence of inflammatory bowel disease (IBD) within the Canadian province of Manitoba and to analyze sociodemographic factors associated with these variations. The authors used the Manitoba Health insurance databases to measure incidence rates of Crohn's disease and ulcerative colitis for each of 52 postal areas in Manitoba, in 1987-1996. The sociodemographic characteristics of the postal areas were based on data from the 1996 Canadian census. The overall incidence rates of Crohn's disease and ulcerative colitis were identical-15.6 per 100,000. Both diseases showed substantial geographic variation, with incidence rates differing significantly from the provincial average in 15 postal areas for Crohn's disease and in 13 postal areas for ulcerative colitis. There was a significant geographic correlation in the incidence of Crohn's disease and ulcerative colitis (r = 0.49, p < 0.001). The incidence of IBD was higher in urban areas (incidence rate ratio (IRR) = 1.21, 95% confidence interval (CI): 1.00, 1.45). Aboriginal Canadians had significantly lower rates of both Crohn's disease (IRR = 0.11, 95% CI: 0.05, 0.22) and ulcerative colitis (IRR = 0.57, 95% CI: 0.42, 0.79). A higher incidence of IBD was ecologically associated with a higher average family income, a lower proportion of immigrant and Aboriginal Canadian populations, and a smaller average family size.

Adult↗
PubMed2001

CD4 T cells monospecific to ovalbumin produced by Escherichia coli can induce colitis upon transfer to BALB/c and SCID mice.

Although some animal models suggest an involvement of CD4 T cells reactive to luminal microbial antigen(s) for the pathogenesis of inflammatory bowel diseases (IBD), direct linkage between microflora-driven clonal expansion of CD4 T cells and the development of colitis has not been well studied. Here, BALB/c and SCID mice were given CD4 T cells purified from Rag-2(-/-) mice crossed to transgenic mice expressing TCR specific to ovalbumin (OVA) then administered with antibiotic-resistant Escherichia coli producing OVA (ECOVA) or LacZ (ECLacZ) via the rectum. The ECOVA-inoculated BALB/c and SCID mice developed a subacute colitis with microscopic features of distortion of crypt architecture, loss of goblet cells, and focal infiltration by mononuclear cells in the lamina propria (LP) and submucosa. Expanding OVA-specific CD4 T cells were detected in colonic follicles of mice with ECOVA. Early in colitis, OVA-specific CD4 T cells producing IFN-gamma predominate in the LP of the colon, which was followed by an emergence of OVA-specific CD4 T cells producing IL-4 and IL-10 at a later time point. Co-transfer of an IL-10-secreting OVA-specific CD4 T cell line prevented colitis. Thus, an expansion of CD4 T cells monospecific to OVA, an antigen non-cross-reactive to colonic tissue, can mediate both induction and inhibition of the colitis which was associated with hyperplasia of lymph follicles.

Administration, Rectal↗
PubMed2004

Regulation of chronic colitis in athymic nu/nu (nude) mice.

The objective of this study was to assess the roles of NK cells, B cells and/or intraepithelial lymphocytes (IEL) in suppressing the development of colitis in nude mice reconstituted with CD4(+)CD45RB(high) T cells. BALB/c nude mice were lethally irradiated and reconstituted with bone marrow from different immunodeficient mice to generate athymic chimeras devoid of one or more lymphocyte populations. Transfer of CD4(+)C45RB(high) T cells into chimeric recipients devoid of B cells, T cells and IEL produced severe colitis within 6-8 weeks, whereas transfer of these same T cells into B cell- and T cell-deficient or T cell-deficient chimeras produced little to no gut inflammation. In addition, we found that nude mice depleted of NK cells or RAG-1(-/-) mice reconstituted with IEL failed to develop colitis following transfer of CD45RB(high) T cells. Severe colitis could, however, be induced in nude mice by transfer of activated/T(h)1 CD4(+)CD45RB(low) T cells. Taken together, our data suggest that IEL, but not B cells or NK cells, play an important role in suppressing the development of chronic colitis in this model. In addition, our data demonstrate that suppression of disease may be due to polarization of naive CD4(+) cells toward a non-pathogenic and/or regulatory phenotype.

Adoptive Transfer↗
PubMed2004

Resistant starch modulates in vivo colonic butyrate uptake and its oxidation in rats with dextran sulfate sodium-induced colitis.

We previously demonstrated improvements of colonic lesions due to dextran sulfate sodium (DSS) in rats after 7 d of supplementation with resistant starch (RS) type 3, a substrate yielding high levels of butyrate (C(4)), a colonic cell fuel source. In the present study, we hypothesized that if inflammation is related to decreased C(4) utilization by the colonic mucosa, RS supplementation should restore C(4) use simultaneously with an increase in the amount of C(4) present in the digestive tract. Hence, we compared, in vivo, the cecocolonic uptake of C(4) and its oxidation into CO(2) and ketone bodies in control and DSS-treated rats fed a fiber-free basal diet (BD) or a RS-supplemented diet. Sprague-Dawley rats (n = 60) were used. DSS treatment was performed to induce acute colitis and then to maintain chronic colitis. After cecal infusion of [1-(13)C]-C(4) (20 micro mol in 1 h), concentrations and (13)C-enrichment of C(4), ketone bodies, and CO(2) were quantified in the abdominal aorta and portal vein. Portal blood flow was recorded. During acute colitis, (13)C(4) uptake and (13)CO(2) production were lower in DSS rats than in controls. During chronic colitis, DSS rats did not differ from controls. After 7 d of chronic colitis, RS-DSS rats exhibited the same C(4) uptake as BD-DSS rats in spite of higher C(4) cecocolonic disposal. After 14 d, C(4) uptake was higher in RS-DSS than in BD-DSS rats. Thus, the increased utilization of C(4) by the mucosa is subsequent to evidence of healing and appears to be a consequence rather than a cause of this RS healing effect.

Acute Disease↗
PubMed1999

Birth-cohort phenomenon in the time trends of mortality from ulcerative colitis.

It has been suggested that the mortality trends of ulcerative colitis in England and Wales are shaped by an underlying birth-cohort phenomenon. This pattern implies that exposure to an environmental risk factor early in life plays a crucial role in the development of the disease. The authors tested whether the birth-cohort pattern is unique to British mortality statistics or a common feature of ulcerative colitis in western countries by using the vital statistics from England and Wales, Canada, Scotland, Switzerland, The Netherlands, and the United States. Ulcerative colitis death rates from the six countries were plotted against the periods of death or periods of birth. Mortality from ulcerative colitis increased in successive generations born throughout the second half of the 19th century. It peaked in subjects born between 1880 and 1890 and has declined since then. Strikingly similar patterns were found in the six countries and when women and men were analyzed separately. The birth-cohort pattern indicates that development of ulcerative colitis is strongly influenced by one or several environmental risk factors, which act during a short period early in life. In western countries, exposure to this risk has changed in a similar fashion.

Age Distribution↗
PubMed1979

Pathology of salmonella colitis.

Salmonella colitis was encountered in eight patients. In seven, the disorder simulated ulcerative colitis both clinically and radiologically. The salmonella infection in the eighth patient was superimposed upon hitherto unrecognized ulcerative colitis. In mild cases the histological appearances of rectal biopsies were nonspecific, consisting of edema of the mucosa with focal inflammatory cell infiltration. More severe cases were characterized by neutrophils infiltrating the walls of degenerating crypts, and in one case there were microthrombi in the mucosa. One patient who was thought to have fulminant ulcerative colitis had a hemicolectomy. The resected specimen exhibited marked hemorrhage and ulceration. There were crypt abscesses in unulcerated areas but there was also extensive necrosis of the mucosa, hemorrhage in the mucosa and submucosa, and microthrombi extending from small vessels in the mucosa into venules in the submucosa similar to the picture seen in acute ischemic colitis. In this case there was intense edema and inflammation in the submucosa as well as in the mucosa.

Abscess↗
PubMed2000

Genetic alterations in chronic ulcerative colitis-associated adenoma-like DALMs are similar to non-colitic sporadic adenomas.

Recent molecular studies have shown that there are differences in the prevalence and timing of certain molecular events between chronic ulcerative colitis (CUC)-associated dysplastic lesions and non-CUC-related sporadic adenomas. However, little is known regarding the molecular features of a specific subtype of CUC-related dysplasia-associated lesion or mass (DALM) that clinically, endoscopically, and pathologically resemble sporadic adenomas, and whether these lesions can be separated from non-CUC-related sporadic adenomas on the basis of their molecular genotype. Therefore, the purpose of this study was to evaluate loss of heterozygosity (LOH) of 3p, APC, and p16 in a specific group of CUC-associated "adenoma-like" DALMs and to compare the results of this tumor with those in a well-defined group of CUC-associated non-adenoma-like DALMs and non-CUC-associated sporadic adenomas. Polypectomy or resection specimens from 21 CUC patients with an adenoma-like DALM, 8 CUC patients with at least one nonadenoma-like DALM (12 lesions in total), and 23 non-CUC patients with a sporadic adenoma were evaluated for LOH of 3p, APC, and p16 by PCR analysis. The results were compared among the three different study groups and correlated with the clinical features of the patients and the pathology of their tumors. Chronic ulcerative colitis-associated adenoma-like DALMs showed LOH of 3p in five of 18 (28%) cases. This value was not significantly different from the 5% of non-CUC sporadic adenomas (p = 0.14) that were positive. However, 50% of CUC-associated non-adenoma-like DALMs were positive for LOH of 3p, and this value was significantly higher (p = 0.01) than the other groups. The frequency of LOH of APC did not differ significantly between the three patient groups (33%, 33%, and 43% in the three groups, respectively). Similar to the 3p results, CUC-associated adenoma-like DALMs and non-CUC-associated sporadic adenomas showed a similar low frequency of positivity for LOH of p16 (5% and 4%, respectively) in comparison to 56% of CUC-associated non-adenoma-like DALMs (p = 0.003). For all markers, no significant differences were detected in the CUC-associated adenoma-like DALM group between lesions that occurred within colitis compared with those that occurred in areas not involved by colitis. Chronic ulcerative colitis-associated non-adenoma-like DALMs have a different molecular genotype than CUC-related adenoma-like DALMs and non-CUC sporadic adenomas. Our data also suggests that the latter two groups of neoplasms may in fact represent a similar, if not identical, pathogenetic entity.

Adenomatous Polyps↗
PubMed2002

Histopathology of ulcerative colitis in initial rectal biopsy in children.

Definitive histologic diagnosis of ulcerative colitis relies upon mucosal architectural distortion and inflammation in the appropriate clinical setting. Although crypt branching, atrophy, and loss are usually present in first biopsies from adults with ulcerative colitis, it has been our impression that features of chronicity are often lacking in first biopsies from children. To test this hypothesis, initial rectal biopsies and follow-up biopsies and/or colonic resections from 53 children (age 15 months to 17 years) and 38 adults (age 21-76 years) with ulcerative colitis were examined in a blinded fashion for villiform surface, crypt atrophy, branching crypts, lamina propria inflammation, crypt abscesses, cryptitis, and basal plasma cells. Mucosal architecture was classified as normal, focally abnormal, or diffusely abnormal. Medical records were reviewed for confirmatory evidence of ulcerative colitis and for duration of symptoms before biopsy. In 87 of 91 biopsies, the lamina propria contained a mixed inflammatory infiltrate. Crypt abscesses and cryptitis were common in both groups. Initial biopsies from children were less likely to show diffuse architectural abnormalities (17 of 53, 32.1%) compared with biopsies from adults (22 of 38, 57.9% p <0.05). Duration of symptoms before diagnosis was significantly shorter in children (mean 17.5 weeks) compared with adults (mean 54.9 weeks). In summary, initial rectal biopsies from children with ulcerative colitis are less likely to show diagnostic mucosal architectural distortion than biopsies from adults. This difference may be related to a shorter duration of symptoms before biopsy.

Adolescent↗
PubMed1992

The interrelation between sclerosing cholangitis and ulcerative colitis in patients undergoing liver transplantation.

Thirty-six patients underwent orthotopic liver transplantation (OLT) for primary sclerosing cholangitis under cyclosporine, azathioprine, and steroid immunosuppression. Of these patients, 29 suffered from chronic ulcerative colitis. The purpose of this study is to determine (1) whether replacement of the diseased liver and the altered immunocompetence suppresses the manifestation of chronic ulcerative colitis, and (2) if active colonic disease alters allograft function. Thirty of 36 patients survived OLT. After OLT, seven of 14 patients with symptomatic colon disease at the time of transplantation continue to suffer from active chronic ulcerative colitis, and three of 13 who were asymptomatic developed clinically active disease. Intractable colonic disease was the indication for post-OLT proctocolectomy in three patients, and one refused an indicated colectomy. Despite the long duration of the disease, none developed colonic malignancy. Long-term graft assessment showed good hepatocyte synthetic function in patients suffering from either active or inactive disease. Liver alkaline phosphatase, however, was significantly higher in patients suffering from active colonic disease. Furthermore, the alkaline phosphatase in symptomatic patients was higher than that seen in a matched cohort undergoing OLT for chronic active hepatitis or primary biliary cirrhosis. These results suggest that (1) liver replacement and immunosuppression in patients suffering from sclerosing cholangitis and ulcerative colitis do not alter the course of the colon disease, and (2) active chronic ulcerative colitis does not adversely affect allograft function, although elevation of alkaline phosphatase may be the harbinger of recurrence over the long term.

Adult↗
PubMed1986

Managing the cancer risk in chronic ulcerative colitis. A decision-analytic approach.

Chronic ulcerative colitis is associated with a high risk of colon cancer. The most appropriate management--prophylactic proctocolectomy or medical surveillance--is, at present, unclear. Recent reports suggest that the presence of colonic dysplasia or "precancer" on endoscopic biopsy may be a reliable predictor of concurrent or future colon cancer. To assess the value of colonic dysplasia in managing colitis patients, I applied decision analytic techniques to currently available data regarding the sensitivity and specificity of colonic dysplasia in colitis patients. Such analysis shows that management based on biopsy for colonic dysplasia, rather than prophylactic proctocolectomy for all colitis patients, will maximize 5-year survival. Sensitivity analysis suggests that management is primarily determined by the sensitivity of biopsy-diagnosed dysplasia--elective prophylactic surgery would be preferred only when sensitivity of dysplasia on biopsy is less than or equal to 0.70 at 20 years, or less than or equal to 0.85 at 30 years of colitis, and changing surgical mortality and survival benefit from early diagnosis within a range established by previous studies affects management decisions only when sensitivity of dysplasia is at the lower end of its reported range.

Biopsy↗
PubMed1986

Colitis after Hibiclens enema.

Acute colitis occurred after a Hibiclens cleanser enema. Endoscopic and histologic features were not helpful in distinguishing this colitis from an infectious or idiopathic colitis, and a careful history proved invaluable. We review the complications of using soapsuds and various chemical-containing enemas; these complications range from mild colitis to death. Because soap and other chemicals are damaging to colonic mucosa, these enemas should be included as a cause of acute colitis.

Biopsy↗
PubMed1991

Prevalence of ulcerative colitis in the Israeli kibbutz population.

We carried out an epidemiological study of ulcerative colitis in 279 Israeli kibbutzim (121,403 population). The prevalence on December 31, 1987 was 121.08 per 100,000 population. When the data were stratified according to ethnic groups, the highest point prevalence was found in Israeli-born Jews (220.56 per 100,000 population), more than in Asian-African-born, or European-American-born kibbutz members (139.20 and 78.73 cases per 100,000 population, respectively). There were 68 men and 78 women (ratio of 0.87). The average age of the patients in the year of this survey was 46 years; it was 35 years at the time of diagnosis. Proctitis was found in 57%, left-sided colitis in 12%, and substantial or total colitis in 31%. Relapse at pregnancy was demonstrated in seven patients, and remission in one. Family history of a first-degree relative with inflammatory bowel disease was documented in three patients (2%). Probable complications of ulcerative colitis were observed in 38 (26%), anemia in 13 (9%). One patient (0.7%) with rectal cancer, also had breast cancer. We suggest that the impressive increase in ulcerative colitis prevalence among Israeli and Asian-African-born, in comparison with European-American-born kibbutz members, points toward a role of environmental factors in the etiology of this disease.

Adult↗
PubMed1997

Azathioprine in steroid-resistant and steroid-dependent ulcerative colitis.

We evaluated, retrospectively, the outcome of 56 patients (39 male, 17 female; mean age, 34 years; age range, 14-65 years) who received azathioprine for either steroid-resistant (group A, n = 10) or steroid-dependent (group B, n = 46) ulcerative colitis. The patients were followed for a mean of 29 +/- 17 months (median, 27 months). Twenty-four had left-sided colitis, 5 had subtotal colitis, and 27 had total colitis. The mean duration of the disease was 51 months (range, 2-192 months). At the beginning of azathioprine treatment (time 0), all patients had clinically severe disease and were taking 40 mg prednisolone per day. Azathioprine was used in addition to steroid therapy at a dosage of 2 mg/kg. The need for steroids, expressed as the median cumulative steroid dose (mg/year), and the number of clinical relapses (requiring steroid therapy) in the 2 years before azathioprine treatment, were compared with those of the 3-year follow-up with azathioprine treatment. A positive response to azathioprine was defined as (a) avoidance of colectomy, (b) a significant decrease in the median cumulative steroid dose, and (c) a significant decrease in the number of clinical relapses (expressed as number/patient/year). One patient in group A withdrew due to painful dyspepsia, and two patients in group B were lost to follow-up. Remission with complete elimination of steroids was achieved in 36 of 53 (64%), 23 of 35 (66%), and 18 of 26 (69%) patients in the first, second, and third years, respectively, of azathioprine treatment. Compared with the 2 years before azathioprine treatment, a significant decrease was observed of about 75% both in steroid consumption and in the number of clinical relapses during the 3 years of azathioprine therapy. Two of nine patients in group A and 2 of 44 patients in group B had colectomy after mean periods of 15 months and 24 months, respectively. Azathioprine is effective and safe in avoiding colectomy in patients with steroid-resistant and steroid-dependent ulcerative colitis; its use decreases both steroid requirements and clinical relapses.

Adolescent↗