Self-expanding Polyflex plastic stents in esophageal disease: various indications, complications, and outcomes.

BACKGROUND: Esophageal stenting has become an important technique in the treatment of different clinical problems such as malignant or benign stenosis, anastomotic leaks after surgery, or fistulas. In this study we present our experience with the self-expanding Polyflex plastic stent in various indications, arising complications, and patient's outcomes. METHODS: Over a three-year period, 35 patients underwent self-expanding Polyflex plastic stent placement for esophageal stenosis (n = 23) with 22 malignant, and for perforations, fistulas, or anastomotic leaks after surgery (n = 12). The short-term efficacy and long-term outcomes were analyzed. RESULTS: In patients with stenosis, implantation was performed without any complications in 91% (21/23). In one patient perforation occurred while passing the stenosis; in another patient the stent dislocated during the insertion procedure. Dysphagia score improved from 3.0 to 1.0 after stenting. In all patients with perforations, fistulas, or anastomotic leaks (n = 12), stents were placed successfully without any complication. Complete sealing of the mucosal defect was proven by radiography in 92% (n = 11) and healing was seen in 42% (n = 5). If indicated, stent removal was performed without any complications. Stent migration (n = 13; 37%) was the most common long-term complication. CONCLUSIONS: The placement of self-expanding Polyflex plastic stents is a highly sufficient and cost-effective treatment for malignant and benign esophageal disorders. Because the long-term results were highly favorable, self-expanding plastic stent placement could be used as the initial treatment for various conditions.

Acceptance of flexible sigmoidoscopy as a screening examination for colorectal cancer in an outpatient clinic.

BACKGROUND AND STUDY AIM: Flexible sigmoidoscopy (FS) is a feasible examination technique and a suitable tool for population-based screening, but very little is known about determinants of endoscopic screening participation. The aim of this study was to determine the acceptance rate and the factors influencing the decision of participating in a screening program for patients in an outpatient clinic. MATERIALS AND METHODS: In this prospective study, a colorectal cancer screening by FS was offered to 631 patients older than 40 years. Three strategies were available, (1) to have the endoscopy on the same day, (2) to make an appointment for another day, or (3) to take time to think about if they wanted the procedure. The reasons for refusal of the FS were documented. RESULTS: 419 of the 631 (66.4%) patients had no interest to take part in the screening program during their outpatient visit. Two hundred twelve (33.6%) patients were primarily interested on FS, but only 110 of them were finally examined. In total, 102 patients did not make an appointment for FS or did not appear for the endoscopy. The participation rate was therefore 17.4% (110/631) of all patients. Of the patients who agreed to receive an on-site examination, 78.3% were examined compared to 18.8% of patients who fixed the appointment for another day or after taking time to reflect upon the FS procedure. More male than female patients accepted the FS screening. Recommended colonoscopy was finally performed in 76%. Thirty-three polyps were found during the screening program of which 18 were larger than 0.5 cm. No CRC was detected. All patients agreed to repeat the FS every 5 years. CONCLUSIONS: This study demonstrates that a screening examination will be most likely performed if it is done as an on-site examination. In contrast, the participation rate is low if the patient has to make an appointment by himself. Acceptance of FS screening is also dependent on the patient's gender and family history of cancer. Additional strategies are needed to further improve participation.

PCR/DGGE and 16S rRNA gene library analysis of the colonic microbiota of HLA-B27/beta2-microglobulin transgenic rats.

AIMS: To determine the phylogenetic composition of the colonic microbiota of transgenic (TG) HLA-B27 rats using 16S ribosomal RNA (rRNA) gene sequences obtained from denaturing gradient gel electrophoresis (DGGE) gels and sequences from a 16S rRNA gene library. METHODS AND RESULTS: Colonic microbiota of TG and nontransgenic (NT) rats harboured by 10-week-old and 6-month-old animals was screened using PCR/DGGE. Six months old TG rats had marked inflammation of the colon compared with 10-week-old TG and NT rats. The DGGE profiles of rats with inflamed colon were similar from rat to rat (Dice's Similarity Coefficient proximal colon 73%, distal colon 83%) whereas profiles from animals without inflammation were dissimilar (52-64%). Identifications of bacterial origins of 16S rRNA gene sequences obtained from DGGE gels (200 bp) and from 16S rRNA clones (450 bp) of the colonic microbiota of diseased rats gave sequences most closely phylogenetically affiliated with uncultured or unknown bacteria. CONCLUSIONS: PCR/DGGE was shown to be an effective method to compare the colonic microbiota composition of TG and NT rats relative to the progression of inflammatory disease. Sequencing of 16S rRNA gene fragments from DGGE gels or 16S rRNA gene clones from a random library showed that uncultured or unknown bacteria were most commonly detected by both methods. It can be concluded that it would be better in future studies to search for the antigens produced by the gut microbiota against which the dysfunctional immune system reacts rather than seek phylogenetic associations. SIGNIFICANCE AND IMPACT OF THE STUDY: PCR/DGGE can be used as a rapid initial screening method to compare the composition of bacterial communities of initially unknown composition that are associated with the development of intestinal disease.

Influence of intestinal bacteria on induction of regulatory T cells: lessons from a transfer model of colitis.

BACKGROUND: The resident flora plays a critical role in initiation and perpetuation of intestinal inflammation, as demonstrated in experimental models of colitis where animals fail to develop disease under germ free conditions. However, the importance of exposure to commensal bacteria before the onset of colitis is unclear. Our aim was to investigate the influence of previous exposure of donor animals to bacterial antigens on colitis development using a transfer model. METHODS: Clinical course and histology were evaluated after transfer of CD4(+)CD62L(+) lymphocytes from germ free and conventionally housed donor mice into SCID recipients. Cotransfer of CD4(+)CD62L(+) cells with CD4(+)CD62L(- )lymphocytes from both groups of mice was initiated. Lymphocytes were analysed by FACS, polarisation potential of cells determined, and cytokines measured within the supernatant by enzyme linked immunosorbent assay. RESULTS: Animals that received cells from germ free donors developed an earlier onset of colitis compared with mice reconstituted with lymphocytes from conventionally housed animals. Additionally, CD4(+)CD62L(- )cells from germ free mice were not able to abrogate colitis induced by cotransfer with CD4(+)CD62L(+) lymphocytes whereas CD4(+)CD62L(- )T cells from normal mice ameliorated disease. The higher percentage of CD4(+)GITR(+) expressing lymphocytes and the production of interleukin 10 after priming by dendritic cells suggests the presence of T(reg) cells within the CD4(+)CD62L(+) lymphocyte subset derived from conventional housed mice and assumes a lack of T(reg) cells within germ free mice. CONCLUSION: The results indicate that bacterial antigens are crucial for the generation and/or expansion of T(reg) cells in a healthy individual. Therefore, bacterial colonisation is of great importance in maintaining the immunological balance.

In vivo CpG DNA/toll-like receptor 9 interaction induces regulatory properties in CD4+CD62L+ T cells which prevent intestinal inflammation in the SCID transfer model of colitis.

BACKGROUND AND METHODS: Cytosin-guanosin dinucleotide (CpG) motifs of bacterial DNA are known to be potent activators of innate immunity. We have shown previously that administration of CpG containing oligodeoxynucleotide (CpG-ODN) to mice before the onset of dextran sodium sulphate induced colitis ameliorated colitis and inhibited induction of proinflammatory cytokines. To investigate the possible involvement of CD4(+) T cells in the prophylactic CpG-ODN effects, we used the SCID transfer model of colitis. RESULTS: CD4(+)CD62L(+) T cells from CpG-ODN treated donors did not induce significant intestinal inflammation in SCID recipients, in contrast with control cells. Additionally, cotransfer of these cells with CD4(+)CD62L(+) cells from normal mice protected recipient animals from colitis, indicating regulatory activity. Also, CD4(+)CD62L(+) cells from toll-like receptor 9 deficient animals induced a significantly more severe colitis in SCID recipients than cells from wild-type littermate controls, suggesting a similar protective role of "endogenous" bacterial DNA leading to a less "aggressive" phenotype of these cells. There was no detectable difference in regulatory T cell surface markers between aggressive and attenuated cell pools but attenuated cell pools showed reduced proliferation in vitro and in vivo and produced less interferon gamma, interleukin (IL)-5, and IL-6 after anti-CD3 stimulation. CONCLUSIONS: Collectively, our data support the concept that both endogenous bacterial DNA and exogenously supplied CpG motifs of bacterial DNA induce regulatory properties in CD4(+) T cells. Therefore, bacterial DNA derived from the normal gut flora may contribute essentially to the homeostasis between effector and regulatory immune mechanisms in healthy individuals to protect them from chronic intestinal inflammation.

Comparison of magnetic resonance imaging colonography with conventional colonoscopy for the assessment of intestinal inflammation in patients with inflammatory bowel disease: a feasibility study.

AIM: Magnetic resonance imaging (MRI) based colonography represents a new imaging tool which has mainly been investigated for polyp screening. To evaluate this approach for patients with inflammatory bowel disease (IBD), we compared MRI based colonography with conventional colonoscopy for assessing the presence and extent of colonic inflammation. PATIENTS AND METHODS: In 22 consecutive patients with suspected or known IBD, MRI colonography was performed immediately before conventional colonoscopy. After bowel cleansing, a T1 positive contrast agent was applied rectally. In addition to T2 weighted sequences, T1 weighted two dimensional and three dimensional Flash acquisitions as well as volume rendered virtual endoscopy were performed. All images were evaluated with regard to typical MRI features of inflammation. The results were compared with colonoscopy findings. RESULTS: Distension and image quality was assessed as good to fair in 97.4% of all colonic segments. Only four of 154 segments were considered non-diagnostic. With colonoscopy serving as the gold standard, the sensitivity for correctly identifying inflammation on a per segment analysis of the colon was 31.6% for Crohn's disease (CD) and 58.8% for ulcerative colitis (UC). In CD, in most cases mild inflammation was not diagnosed by MRI while in UC even severe inflammation was not always depicted by MRI. Virtual endoscopy did not add any relevant information. CONCLUSION: MRI based colonography is not suitable for adequately assessing the extent of colonic inflammation in patients with IBD. Only severe colonic inflammation in patients with CD can be sufficiently visualised.

Use of self-expandable plastic stents for the treatment of esophageal perforations and symptomatic anastomotic leaks.

BACKGROUND AND STUDY AIMS: Extensive anastomotic leaks after esophageal resection and esophageal perforations are a therapeutic challenge. The aim of the present study was to assess the potential of the self-expandable Polyflex plastic stent for the treatment of these conditions. PATIENTS AND METHODS: Between January 2002 and March 2003, nine patients were treated with a self-expandable Polyflex plastic stent for sealing of thoracic esophagoenteric anastomotic leaks following surgical resection (n = 5) or esophageal perforation (n = 4). RESULTS: In all patients the stents were inserted successfully without technical problems. In all but two patients complete sealing of the leak was achieved as demonstrated by radiography with water-soluble contrast media. The stent migration rate was 30 % and repositioning of the migrated stents was possible in all cases. Complete mucosal healing of the esophageal leaks and stent extraction was achieved in six patients. The stents were in situ for an average period of 135 +/- 78 days. Two critically ill patients with anastomotic leaks died in spite of stent insertion due to sepsis and one patient with esophageal perforation died due to the underlying malignant disease. CONCLUSIONS: Our preliminary experience with the self-expanding and removable Polyflex plastic stent for the sealing of anastomotic leaks and esophageal perforations suggests that this stent is a feasible treatment option, in particular, for more extensive esophageal defects, patients with co-morbid conditions, and critically ill patients.

Effects of feeding a probiotic preparation (SIM) containing inulin on the severity of colitis and on the composition of the intestinal microflora in HLA-B27 transgenic rats.

An overly aggressive immune response to the intestinal microflora in a genetically susceptible host background has been implicated in the pathogenesis of inflammatory bowel diseases. We measured the impact of a probiotic preparation (SIM) containing inulin on the severity of colitis and on intestinal microflora profiles of HLA-B27-beta(2)-microglobulin transgenic (TG) rats. SIM is a mixture of lactobacilli, bifidobacteria, and inulin. Two-month-old TG rats received either SIM or water. Control TG rats received metronidazole, alone or in combination with SIM, for 8 weeks. Nontransgenic rats received SIM or water. The cecal content was removed for analysis of the intestinal microflora by PCR combined with denaturing gradient gel electrophoresis. The colon was scored for histological evidence of inflammation, colonic myeloperoxidase activity and interleukin-1beta RNA levels were measured photometrically or by real-time quantitative PCR. At 4 months, the colonic inflammation of TG rats treated with SIM was histologically diminished compared to that in untreated TG rats (2.2 +/- 0.2 versus 2.9 +/- 0.1; P

[Extraintestinal manifestations in chronic inflammatory bowel diseases]. / Extraintestinale Manifestationen bei chronisch entzündlichen Darmerkrankungen.

60-80% of patients with inflammatory bowel diseases (IBD) develop extraintestinal manifestations. These complications are mostly the result of the underlying disease, deficiencies, or drug therapy and can significantly reduce the quality of life of patients with IBD. The most evident manifestations affect the perianal region, joints, skin, and eyes. Regular check-ups and early substitution in addition to a consistent therapy of the chronic intestinal inflammation usually lead to a significant reduction of the extraintestinal symptoms.

Protoporphyrin IX distribution following local application of 5-aminolevulinic acid and its esterified derivatives in the tissue layers of the normal rat colon.

Photodynamic diagnosis and especially therapy after sensitization with 5-aminolevulinic acid (ALA) is hampered by limitations of uptake and distribution of ALA due to its hydrophilic nature. Chemical modification of ALA into its more lipophilic esters seems to be promising to overcome these problems. The aim of the present study was to investigate the comparative kinetics of protoporphyrin IX (PPIX) fluorescence in rat colonic tissue after topical application of ALA and its esterified derivatives, ALA-hexylester (h-ALA), ALA-methylester (m-ALA) and ALA-benzylester (b-ALA). Fluorescence intensity induced by PPIX in normal colonic tissue was quantified using fluorescence microscopy at 1, 2, 4, 6 and 8 h after sensitization. Mucosa exhibited higher fluorescence levels compared to the underlying submucosa or smooth muscle. Peak fluorescence intensities were seen 4 h after local sensitization with 86.0 mol ml(-1) ALA (513 +/- 0.57 counts per pixel), 6.6 mol ml(-1) m-ALA (508 +/- 35.50) and 4.8 mol ml(-1) h-ALA (532 +/- 128.80), and 6 h after sensitization with 4.6 mol ml(-1) b-ALA (468 +/- 190.27). A 13-18 times lower concentration of ALA esters was required for fluorescence intensities reached with ALA alone. A similar degree of the fluorescence ratio between mucosa and muscularis (5-6:1) was detected for ALA and its derivatives. The time point of the maximum value of this ratio was consistent with peak fluorescence levels for ALA and each ALA-ester. The clinical feasibility and the advantages of topical ALA ester-based fluorescence for detection of malignant and premalignant lesions need further investigations.

Different subsets of enteric bacteria induce and perpetuate experimental colitis in rats and mice.

Resident bacteria are incriminated in the pathogenesis of experimental colitis and inflammatory bowel diseases. We investigated the relative roles of various enteric bacteria populations in the induction and perpetuation of experimental colitis. HLA-B27 transgenic rats received antibiotics (ciprofloxacin, metronidazole, or vancomycin-imipenem) in drinking water or water alone in either prevention or treatment protocols. Mice were treated similarly with metronidazole or vancomycin-imipenem before or after receiving 5% dextran sodium sulfate (DSS). Germfree transgenic rats were colonized with specific-pathogen-free enteric bacteria grown overnight either in anaerobic or aerobic atmospheres. Nontransgenic rats colonized with anaerobic bacteria served as negative controls. Although preventive metronidazole significantly attenuated colitis in transgenic rats and DSS-treated mice, it had no therapeutic benefit once colitis was established. Ciprofloxacin also partially prevented but did not treat colitis in B27 transgenic rats. In both animal models vancomycin-imipenem most effectively prevented and treated colitis. Germfree transgenic rats reconstituted with enteric bacteria grown under anaerobic conditions had more aggressive colitis than those associated with aerobic bacteria. These results suggest that a subset of resident luminal bacteria induces colitis, but that a complex interaction of commensal aerobic and anaerobic bacteria provides the constant antigenic drive for chronic immune-mediated colonic inflammation.

Nuclear factor-kappa B activity and intestinal inflammation in dextran sulphate sodium (DSS)-induced colitis in mice is suppressed by gliotoxin.

In acute DSS-induced colitis nuclear factor (NF)-kappaB-dependent inflammatory cytokines including IL-1 and tumour necrosis factor-alpha (TNF-alpha) are up-regulated. Here we examined the effects of gliotoxin, a fungal metabolite known to inhibit NF-kappaB activity, on cytokine production by a mouse cell system in vitro and on intestinal inflammation and NF-kappaB activation in vivo. In vitro gliotoxin decreased TNF-alpha gene expression and protein production by RAW-264.7 mouse macrophage-like cells stimulated with lipopolysaccharide. In vivo, gliotoxin treatment of mice was begun on day 3 of 5% DSS application dissolved in the drinking water and continued until day 8. Gliotoxin treatment dose-dependently down-regulated colonic inflammation as assessed histologically and in parallel there was a suppression of colonic TNF-alpha and IL-1alpha mRNA expression on day 8 as analysed by semiquantitative reverse transcriptase-polymerase chain reaction (P < 0.01). Furthermore, colonic NF-kappaB DNA-binding activity was increased in DSS-induced colitis and was suppressed by gliotoxin. These results demonstrate the essential role of NF-kappaB in DSS-induced colitis and indicate a molecular approach to the treatment of intestinal inflammatory disorders.

Differential induction of colitis and gastritis in HLA-B27 transgenic rats selectively colonized with Bacteroides vulgatus or Escherichia coli.

Resident bacteria play an important role in initiating and perpetuating gastrointestinal inflammation. We previously demonstrated that six commensal bacteria including Bacteroides vulgatus caused more aggressive colitis and gastritis in HLA-B27 transgenic rats than did the other five bacteria without B. vulgatus. This study compared the degree of gastrointestinal inflammation in gnotobiotic HLA-B27 transgenic rats monoassociated with either B. vulgatus or Escherichia coli. Gnotobiotic transgenic rats raised in Trexler isolators were selectively colonized with either B. vulgatus or E. coli. Control rats were either germfree or colonized with six common commensal bacteria (Streptococcus faecium, E. coli, Streptococcus avium, Eubacterium contortum, Peptostreptococcus productus, and B. vulgatus [DESEP-B]). After 1 month, all the rats were killed and tissues were prepared for histologic and biochemical evaluation. Colitis induced by B. vulgatus monoassociation was almost equal to that in DESEP-B-colonized rats and was significantly more severe than E. coli-induced colitis, which was absent by histological testing and mild by colonic myeloperoxidase and interleukin-1beta concentration determinations. However, gastritis was detectable only in DESEP-B-associated rats. These studies suggest that not all resident bacteria have equal proinflammatory capabilities, since B. vulgatus alone is more active than E. coli alone in inducing colitis, and that colitis and gastritis result from different luminal bacterial stimuli.

Varying cecal bacterial loads influences colitis and gastritis in HLA-B27 transgenic rats.

BACKGROUND & AIMS: Recent data support an important role of resident luminal bacteria in experimental colitis. We determined how altered cecal bacterial loads influence colitis and gastritis. METHODS: A cecal self-filling blind loop (SFBL) was created or the cecum was excluded from the fecal stream in specific pathogen-free HLA-B27 transgenic (TG) rats with early colitis and in nontransgenic (nonTG) littermates; controls underwent sham operation (SHAM). Luminal bacterial concentrations were determined by culture and counting chamber. RESULTS: TG rats with SFBL had more severe cecal inflammation and leukocytosis than TG SHAM controls. TG excluded rats with low cecal bacterial loads had no cecal inflammation and less colitis and gastritis than SHAM controls, despite having normal distal colonic and gastric bacterial concentrations. Metronidazole attenuated cecal inflammation and eliminated Bacteroides in SFBL TG rats. NonTG SFBL rats had mild cecal inflammation and no gastritis and colitis. The ratio of total anaerobic to aerobic bacteria was 1000-fold greater in SFBL than in SHAM rats, with a 10,000-fold increased ratio of Bacteroides spp. to aerobes. CONCLUSIONS: The luminal bacterial load and composition determines the activity of cecal inflammation in genetically susceptible hosts. Lowering cecal bacterial concentrations can diminish inflammation in remote organs.

[Initial symptoms, extra-intestinal manifestations and course of pregnancy in chronic inflammatory bowel diseases]. / Erstsymptome, extraintestinale Manifestationen und Schwangerschaftsverlauf bei chronisch entzündlichen Darmerkrankungen.

BACKGROUND: In many cases inflammatory bowel disease is accompanied by extraintestinal manifestations. This results in lowering of live quality. The aim of this study was to gather data retrospectively about initial symptoms, extraintestinal manifestations and course of pregnancy in a large unselected population with inflammatory bowel disease in South Germany. PATIENTS AND METHODS: Data from 1975 to 1989 (392 patients) were analyzed and partially compared with data from 1992 to 1995 (211 patients). RESULTS: Patients with Crohn's disease in average have been 25 years old at the time point of initial symptoms, whereas the age of ulcerative colitis patients was 30 years (p < 0.0001). The number of Crohn's disease patients with a long interval between initial symptoms and diagnosis (> 1 year) was significantly decreased in the second population (50% vs 38%; p < 0.05). Dominant initial symptoms in Crohn's disease were indisposition, abdominal pain and nonbloody diarrhea in contrast to ulcerative colitis which manifested mostly with bloody diarrhea. Extraintestinal manifestations occurred in 76% of patients with Crohn's disease and 64.6% with ulcerative colitis. Complications during the course of pregnancy have been detected in 40.5% in Crohn's disease and 60% in ulcerative colitis. CONCLUSION: A better knowledge of initial symptoms and extraintestinal manifestations in inflammatory bowel disease can help to decrease the interval between initial symptoms and the diagnosis. Pregnancy in patients with inflammatory bowel disease needs to be treated with special care.

[Nutritional deficiencies and complications in chronic inflammatory bowel diseases]. / Mangelzustände und Komplikationen bei chronisch entzündlichen Darmerkrankungen.

BACKGROUND: Deficiencies of vitamins and trace elements are frequent in inflammatory bowel disease. Aim of this study was to evaluate retrospectively the prevalence of these deficiencies and of liver complications in a large population. PATIENTS AND METHODS: The records from 392 out-patients, 279 with Crohn's disease (160 female, 119 male) and 113 with ulcerative colitis (56 female, 57 male) were analyzed. RESULTS: Deficiencies were found in 85% of patients with Crohn's disease vs 68% with ulcerative colitis during the course of the disease, predominantly a deficiency of iron and of calcium. Less frequently deficiencies of zinc, protein, cyanocobalamin, and folic acid were found. Elevated liver enzymes were seen in 38% of patients with Crohn's disease vs 27% with ulcerative colitis. In order of frequency: gamma-glutamyl-transferase, ALAT, AP, ASAT, and bilirubin. Gallstones were present in 12% of patients with Crohn's disease and 4% with ulcerative colitis. 6% of patients with Crohn's disease and 4% with ulcerative colitis had kidney stones. CONCLUSIONS: In view of the high frequency of deficiencies in patients with inflammatory bowel disease it seems to be important to check frequently for extraintestinal complications.

[Acute hemolytic crisis as the initial manifestation of Wilson disease]. / Akute hämolytische Krise als Erstmanifestation eines Morbus Wilson.

A 25-year-old woman who had delivered a normal child after a normal pregnancy four months ago, was suffering from a common cold. The latter was treated by tetracyclines. A few days later she developed an acute severe hemolysis. Moreover she had signs of hepatic failure which was characterized by a considerably reduced synthetic capacity of the liver but low serum aminotransferase levels and a proximal renal tubular disorder. With a negative Coombs test an autoimmune hemolytic anemia was unlikely. Therefore diagnostic procedures were directed at the cause of the liver injury. An increased urinary excretion of copper, strongly elevated levels of liver tissue copper and the detection of a Kayser-Fleischer ring by slit-lamp examination proved the diagnosis of Wilson's disease-presenting clinically only as severe hemolysis. Ceruloplasmin concentration in serum was in low normal range and not diagnostic.

Interleukin 10 suppresses experimental chronic, granulomatous inflammation induced by bacterial cell wall polymers.

BACKGROUND AND AIMS: Interleukin 10 (IL10) inhibits monocyte/macrophage and T lymphocyte effector functions. This study examined the effect of systemically administered IL10 on acute and chronic granulomatous enterocolitis, hepatitis, and arthritis in a rat model. METHODS: Lewis rats were injected intramurally with streptococcal peptidoglycan-polysaccharide (PG-APS) polymers. Beginning 12 hours before PG-APS injection, rats were treated daily with subcutaneous murine recombinant IL10 or vehicle for three or 17 days. RESULTS: IL10 attenuated acute enterocolitis in a dose dependent fashion (p < 0.01). Protective effects were more profound in the chronic granulomatous phase with decreased enterocolitis and markedly inhibited leucocytosis, hepatic granulomas, and chronic erosive arthritis (p < 0.001). IL10 downregulated tissue IL1, IL6, tumour necrosis factor alpha, and interferon gamma gene expression, consistent with the in vitro effects of IL10 on PG-APS-stimulated splenocytes. Caecal IL1 protein concentrations and IL2 and interferon gamma secretion by in vitro stimulated mesenteric lymph nodes were downregulated in IL10 treated animals. CONCLUSIONS: These results indicate that exogenous IL10 can inhibit experimental granulomatous inflammatory responses and suggest that IL10 treatment could be an effective new therapeutic approach in human disorders such as Crohn's disease, rheumatoid arthritis, and sarcoidosis.

Normal luminal bacteria, especially Bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27/human beta2 microglobulin transgenic rats.

Genetic and environmental factors are important in the pathogenesis of clinical and experimental chronic intestinal inflammation. We investigated the influence of normal luminal bacteria and several groups of selected bacterial strains on spontaneous gastrointestinal and systemic inflammation in HLA-B27 transgenic rats. Rats maintained germfree for 3-9 mo were compared with littermates conventionalized with specific pathogen-free bacteria. Subsequently, germfree transgenic rats were colonized with groups of five to eight bacteria that were either facultative or strictly anaerobic. Transgenic germfree rats had no gastroduodenitis, colitis, or arthritis, but developed epididymitis and dermatitis to the same degree as conventionalized rats. Colonic proinflammatory cytokine expression was increased in transgenic conventionalized rats but was undetectable in germfree and nontransgenic rats. Colitis progressively increased over the first 4 wk of bacterial exposure, then plateaued. Only transgenic rats colonized with defined bacterial cocktails which contained Bacteroides spp. had colitis and gastritis. Normal luminal bacteria predictably and uniformly induce chronic colonic, gastric and systemic inflammation in B27 transgenic F344 rats, but all bacterial species do not have equal activities.