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PubMed1997

Colonic nitrite and immunoglobulin G concentrations in dogs with inflammatory bowel disease.

OBJECTIVE: To evaluate lavage analytes as markers of mucosal inflammation in healthy dogs and dogs with inflammatory bowel disease (IBD). DESIGN: Case control study. ANIMALS: 9 healthy dogs and 10 dogs with IBD. PROCEDURE: A polyethylene glycol electrolyte solution was administered into the dogs colons via a rectal balloon catheter prior to colonoscopy. Lavage solution was allowed to remain intraluminally for 30 minutes and then was withdrawn. Lavage supernatant samples were immediately analyzed for total protein, IgG, and nitrite concentrations and myeloperoxidase activity. Mucosal biopsy specimens were obtained from the descending colon and histologically reviewed. RESULTS: All dogs with IBD had mild to severe lymphocytic-plasmacytic colitis, whereas 8 of 9 healthy dogs did not have substantial mucosal inflammation. Myeloperoxidase activity was not detected in lavage samples from healthy dogs or dogs with IBD. Total protein concentration was not significantly different between groups. Mean nitrite and IgG concentrations were significantly higher in samples from dogs with IBD (1.83 nmol/ml and 46 mg/dl, respectively), compared with samples from healthy dogs (0.245 nmol/ml and undetectable concentrations, respectively). Severity of lesions was not correlated with nitrite or IgG concentration. CLINICAL IMPLICATIONS: Assay of nitrite and IgG concentrations in colonic lavage fluid is a simple, objective means of evaluating mucosal inflammation in dogs with IBD. Potential uses include monitoring response to treatment and evaluation of complex cases of chronic intestinal inflammation.

Analysis of Variance↗

PubMed1998

Nutritional issues and therapy in inflammatory bowel disease.

Nutritional issues in inflammatory bowel disease (IBD) often receive inadequate attention both in regard to therapy and nutritionally related complications of IBD. This article reviews much of the research that has evaluated the role of diet in the causation, primary treatment, and adjunctive therapy of both ulcerative colitis (UC) and Crohn's disease (CD). Benefits have been demonstrated in the use of elemental diets or polymeric diets in CD in both acute flare up or maintenance of IBD. A careful team approach can overcome problems in implementing nutritional therapy. Nutrition also has a critical benefit in postoperative CD and perioperative UC. Numerous easily corrected, nutritional abnormalities are often overlooked in patients with IBD, which may have significant consequences. Nutritional therapy may have a central place in the hierarchy of treatment in IBD and further research is critical in this area to better define the benefits of nutrition in IBD.

Adult↗

PubMed1998

Cytokines in inflammatory bowel disease.

Inflammatory bowel disease (IBD) denotes chronic inflammatory disorders of gastrointestinal tract of unknown etiology that comprises 2 major groups: ulcerative colitis (UC) and Crohn's disease (CD). Disregulation of the intestinal immune system both at humoral and cellular level constitutes an important element in the multifactorial pathogenesis of IBD. The expression of pro-inflammatory cytokines, most notably IL-1, IL-6, TNF-alpha and chemokines (IL-8, ENA-78, MCP-1, RANTES) in intestinal mucosa from IBD patients is markedly enhanced, however, it is not always accompanied by increases in cytokines' serum levels. In IBD also significant changes occur in the tissue expression of immunoregulatory cytokines: increased levels of IL-2 mRNA and IFN-gamma mRNA, and decreased expression of IL-4 were found in affected intestinal mucosa. Chronic intestinal lesions of patients with Crohn's disease are associated with a Th1 type cytokine profile. The clinical effectiveness of anti-TNF-alpha antibodies and of IL-10 has been demonstrated in steroid-refractory Crohn's disease patients. The data demonstrating the role of cytokines in the pathogenesis of IBD should be carefully analyzed because of limitations imposed by the patient- and sample-related parameters. Further investigations will clarify the significance of the impairments in cytokine network for the initiation and progression of the IBD.

Animals↗

PubMed2002

Association of ulcerative colitis with the inflammatory bowel disease susceptibility locus IBD2 in non-Jewish Caucasians and evidence of genetic heterogeneity among racial and ethnic populations with Crohn disease.

Genomewide scanning has been used to identify chromosomal regions encoding susceptibility loci to inflammatory bowel disease (IBD). The greatest evidence for linkage to IBD has been reported for a region of chromosome 12q14 surrounding the microsatellite marker D12S83, with a logarithm of odds score of 5.47 and a positive transmission disequilibrium test, and which was subsequently named IBD2. We wished to confirm this locus by genotyping the highly polymorphic microsatellites D12S1022, D12S1056, and D12S83, spanning a continuous region on chromosome 12 of 342 kb, in a cohort of nonrelated individuals with ulcerative colitis (89 patients), Crohn disease (121 patients), and population-based control subjects (100 patients). In non-Jewish Caucasians, one D12S1022 allele, one D12S1056 genotype, and three D12S83 alleles were found to have statistically significant differences in distribution between the two disease groups and the control population. These data support a significant association of IBD with the IBD2 locus in close vicinity to the three markers studied. The replication of genetic risk loci in a case control association study may indicate susceptibility genes in this region and may facilitate identification of candidate genes for IBD. Subgroup analysis revealed a notable difference in genotype distribution among Jewish Caucasian and African American patients affected with Crohn disease when compared with similarly affected non-Jewish Caucasians. Using Fisher exact test, statistically significant distribution differences were observed for D12S1022 and D12S83. These data indicate that there may be significant genetic heterogeneity between different ethnic and racial IBD populations or may simply reflect differences in marker allele frequencies among populations.

Adolescent↗

PubMed1995

Inflammatory bowel disease in primary sclerosing cholangitis: an analysis of patients undergoing liver transplantation.

Fifty-five patients undergoing orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) were reviewed retrospectively. After OLT there were significantly more episodes of acute rejection in 31 patients with a previous history of inflammatory bowel disease (IBD) than in 24 without such a history. Patients who had severe acute rejection were significantly younger at diagnosis of IBD. Five patients with histological features suggestive of recurrent PSC after OLT were significantly younger at the time of transplantation than those who did not develop recurrence. Patients with poor control of IBD after OLT had a significantly lower age at diagnosis of bowel inflammation. The presence of IBD did not affect the outcome after OLT, but was associated with a higher rate of acute rejection. Younger patients had a greater risk of developing severe rejection, recurrent PSC and poor control of IBD after liver transplantation.

Adolescent↗

PubMed2002

Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: potential therapeutic use in the treatment of inflammatory bowel disease.

BACKGROUND: Cytokines involved in inflammatory bowel disease (IBD) direct a predominantly cell-mediated T- helper-1 (Th1) immune response. The nonspecific anti-inflammatory treatment being used in the management of patients with IBD has not changed much since the 1970s and new therapeutic agents are keenly sought. Several compounds isolated from Allium sativum (garlic) modulate leukocyte cell proliferation and cytokine production. METHODS: To investigate the possible therapeutic effects of garlic in the treatment of patients with IBD, whole blood and peripheral blood mononuclear cells (PBMCs) were stimulated in the presence of various concentrations of garlic extract and the effect on leukocyte cytokine production was determined in vitro using multiparameter flow cytometry. RESULTS: Monocyte interleukin (IL)-12 production was inhibited significantly in the presence of low concentrations of garlic extract (>or=0.1 microg/ml total protein). Monocyte IL-10 production increased significantly and monocyte tumor necrosis factor-alpha (TNF-alpha), IL-1alpha, IL-6, IL-8, T-cell interferon-gamma (IFN-gamma), IL-2, and TNF-alpha decreased significantly in the presence of >or=10 microg/ml garlic extract. Twenty to fifty percent of the immunomodulatory activity of garlic extract on cytokine production was acid labile. The inhibitory activity of methylprednisolone, a commonly used anti-inflammatory in IBD, with garlic on leukocyte cytokine production was additive. CONCLUSIONS: By inhibiting Th1 and inflammatory cytokines while upregulating IL-10 production, treatment with garlic extract may help to resolve inflammation associated with IBD. An in vivo animal model study needs to be undertaken to determine the significance of these in vitro findings.

Anti-Inflammatory Agents↗

PubMed2004

Conditional multipoint linkage analysis using affected sib pairs: an alternative approach.

Recently, Liang et al. ([2001b] Genet. Epidemiol. 21:105-122) proposed a conditional approach to assess linkage evidence on the target region by incorporating linkage information from an unlinked (reference) region using allele shared IBD (identity-by-decent) from affected sib pairs. This is carried out by conditioning on the IBD sharing value at the estimated trait locus of the reference region. Since markers considered are typically non-fully informative, the IBD sharing at each marker needs to be estimated (or imputed). In this report, we propose an alternative approach to deal with the IBD sharing in the reference region. This new approach makes full use of the observed data without having to categorize the imputed IBD sharing as needed in Liang et al. ([2001b] Genet. Epidemiol. 21:105-122). We compare these two approaches by simulating data from a variety of two-locus models including heterogeneity, additive and multiplicative with either fully informative markers or non-fully informative markers. The performance of both approaches is quite comparable showing consistent estimates of the trait locus and key genetic parameters.

Alleles↗

PubMed2004

Multipoint linkage analysis of quantitative traits on sex-chromosomes.

Variance component models form a powerful and flexible tool for multipoint linkage analysis of quantitative traits. Estimates of genetic similarity are needed for the variance component model to detect linkage and to locate genes, and two methods are commonly used to calculate multipoint identity-by-descent (IBD) estimates for autosomes. Fulker et al. ([1995] Am. J. Hum. Genet. 56: 1229-1233) and Almasy and Blangero ([1998] Am. J. Hum. Genet. 62: 119-121) used multiple regression to estimate the IBD sharing along a chromosome, while the approach of Kruglyak and Lander ([1995] Am. J. Hum. Genet. 57: 439-454) is based on a hidden Markov model. In this paper, we modify the variance component model to accommodate sex-chromosomes, and we extend both multipoint IBD estimation methods to accommodate sex-linked loci. Simulation studies demonstrate the power and precision of the variance component model to detect QTLs located on the sex-chromosome. The two multipoint IBD estimation methods have the same accuracy to identify QTL position, but the hidden Markov model yields a larger average maximum LOD score to detect linkage than the regression model. The extension of the multipoint IBD estimation methods and the variance component model to the X chromosome shows that the variance component model is a powerful and flexible tool for linkage analysis of quantitative traits on both autosomes and sex-chromosomes.

Algorithms↗

PubMed2007

The Luebeck interview for psychosocial screening in patients with inflammatory bowel disease.

BACKGROUND: Psychosocial factors play an important role in the course of inflammatory bowel disease (IBD). However, a simple, valid psychosocial screening instrument that is suitable for short patient-physician contacts does not exist. Therefore, the Luebeck semistructured Interview for Psychosocial Screening was developed as a rating tool for psychosocial stress in IBD patients (LIPS-IBD). METHOD: The entire interview requires approximately 10 minutes. Interrater reliability was tested. Depression, anxiety, social support, impact of the disease, global level of psychosocial stress, and demand for psychosocial support were rated in 92 patients with IBD on 5 point Likert scales. Patients from the in- and out-patient clinic for gastroenterology were included. In addition, patients filled out self-report questionnaires regarding depression, anxiety, social support, and impact of the disease. Indices of disease activity (Colitis Activity Index, Crohn's Disease Activity Index) were recorded. RESULTS: Both patients and physicians found the interview feasible. Reliability was good, with interrater reliability ranging from .76 to .94. Convergence with self-report instruments was also high (r = .5-.6). Ratings of depression and impact of the disease were correlated with indices of disease activity. DISCUSSION: LIPS helps to identify patients with high levels of psychosocial stress and provide them with more detailed psychologic assessments. It was found to be a suitable instrument for daily clinical routine. It is potentially a valuable screening tool to obtain reliable, valid, and useful information in daily practice in IBD treatment settings.

Adult↗

PubMed2007

Comparative analysis of colonic gene expression of three experimental colitis models mimicking inflammatory bowel disease.

BACKGROUND: Mouse models of inflammatory bowel diseases (IBD) are used to unravel the pathophysiology of IBD and to study new treatment modalities, but their relationship to Crohn's disease (CD) or ulcerative colitis (UC) is speculative. METHODS: Using Agilent mouse TOX oligonucleotide microarrays, we analyzed colonic gene expression profiles in three widely used models of experimental colitis. In 2 of the models (TNBS and DSS-induced colitis), exogenous agents induce the colitis. In the third model the colitis is induced after transfer of a T-cell population (CD4(+)CD45RB(high) T cells) that lacks regulatory cells into an immunodeficient host. RESULTS: Compared with control mice, in DSS, TNBS, and the CD45RB transfer colitis mice, 387, 21, and 582 genes were more than 2-fold upregulated in the intestinal mucosa. Analyses of exclusively shared gene expression profiles between the different models revealed that DSS/transfer colitis share 69 concordantly upregulated genes, DSS/TNBS 6, and TNBS/transfer colitis 1. Seven genes were upregulated in all three models. The CD45RB transfer model expression profile included the most genes that are known to be upregulated in IBD. Of 32 genes that are known to change transcriptional activity in IBD (TNF, IFN-gamma, Ltbeta, IL-6, IL-16, IL-18R1, IL-22, CCR2, 7, CCL2, 3, 4, 5, 7, 11, 17, 20, CXCR3, CXCL1, 5, 10, Mmp3, 7,9, 14, Timp1, Reg3gamma, and Pap, S-100a8, S-100a9, Abcb1, and Ptgs2), 2/32 are upregulated in TNBS, 15/32 are upregulated or downregulated in DSS and 30/32 are upregulated or downregulated in the CD45RB transfer colitis. CONCLUSION: The pattern of gene expression in the CD45RB transfer model most closely reflects altered gene expression in IBD.

Animals↗

PubMed2005

Association between mutations in the CARD15/NOD2 gene and colorectal cancer in a Greek population.

Epidemiological observations suggest that cancer arises from chronically inflamed tissues. Inflammatory bowel disease (IBD) is a typical example since patients with longstanding IBD are at increased risk for development of colorectal cancer (CRC). Therefore, genetic factors predisposing to or implicated in the chronic inflammatory process in IBD may simultaneously predispose to CRC. Recently CARD15/NOD2 has been associated with IBD, which further strengthens the notion that the inflammatory response plays a crucial role in this disease. Several mutations have been identified in the CARD15/NOD2 gene, which appear with significantly higher frequency in patients with IBD. In this report, we have examined the frequency of the 3 major mutations R702W, G908R and 3020insC of the CARD2/NOD2 gene in a series of 104 consecutive Greek patients with sporadic colorectal cancer and 100 healthy individuals. The frequency of all the mutations was significantly elevated compared to the control population (R702W, OR=5.00, p=0.023; G908R, OR=2.78, p=0.025; 3020insC, OR=2.44, p=0.017). Patients with advanced stage tumors were more frequently carriers of at least 1 variant in the CARD15/NOD2 gene (p=0.009). Our results suggest that CARD2/NOD2 may be a genetic factor that predispose to sporadic colorectal cancer.

Aged↗

PubMed2025

Prevalence and predictors of low bone mineral density in pediatric inflammatory bowel disease.

OBJECTIVES: Bone health is at risk in children with inflammatory bowel disease (IBD). This study examined the prevalence and predictors of low bone mineral density (BMD) in a cohort of children and young adults with IBD. METHODS: This single-center retrospective study included patients with IBD, ages 3.5-22 years, with completed dual x-ray absorptiometry (DXA) scans from 2006 to 2019. Demographic, clinical, and laboratory data were collected. Logistic regression analysis identified predictors associated with low BMD (Z-scores ≤ -2 standard deviations [SDs]) for three outcomes. In an overlapping IBD cohort with available genetic data between 2002 and 2019 (n = 378), genetic risk for diminished bone health was calculated using published polygenic risk scores generated from genome-wide association studies based on DXA or heel ultrasound speed of sound (SOS). Linear regression analysis examined associations of low BMD and genetic risk. RESULTS: Low BMD prevalence was 7% in our cohort (n = 600) based on spine bone mineral apparent density (BMAD), which best accounts for growth delays. Median (interquartile range [IQR]) spine BMAD Z-score was -0.37 SD (-1.11 to 0.35). Predictors of low BMAD included lower BMI Z-score (odds ratio [OR]: 0.67, p value: 0.02) and decreased height Z-score (OR: 0.6, p value: 0.005). Of those with longitudinal data (n = 118), low BMI (OR: 0.44, p value: <0.001) and steroid use (OR: 3.42, p value: 0.01) were associated with suboptimal bone health (Z-scores ≤ -1SD). In the cohort with genetic data, heel genomic SOS (β [standard error] = 0.17 [0.35], p ≤ 0.01) was associated with BMD. CONCLUSIONS: Lower BMI should prompt DXA monitoring in pediatric IBD. Genetic predisposition may identify an at-risk subpopulation.

Humans↗

PubMed2003

Epstein-Barr virus infection in colorectal neoplasms associated with inflammatory bowel disease: detection of the virus in lymphomas but not in adenocarcinomas.

Epstein-Barr virus (EBV) is associated with several lymphoid and epithelial human malignancies. The latter include gastric adenocarcinomas, while sporadic colorectal adenocarcinomas (CRCs) have been reported to be EBV-negative. Recently, increased numbers of EBV-infected B lymphocytes have been detected in intestinal mucosal samples affected by ulcerative colitis (UC) and, to a lesser extent, Crohn's disease (CD). Both CRC and colorectal non-Hodgkin's lymphoma (NHL) are recognized complications of inflammatory bowel disease (IBD), but it is unclear to what extent EBV contributes to the development of these neoplasms. Seventeen cases of IBD-associated CRC and nine cases of IBD-associated colorectal NHL were therefore studied for the presence of EBV by in situ hybridization. EBV-positive cases were further studied for the expression of the EBV-encoded nuclear antigen (EBNA) 2 and the latent membrane protein (LMP) 1 of EBV by immunohistochemistry. Four out of seven cases of colorectal NHL associated with UC were shown to be EBV-positive. In addition, two of two colorectal NHLs developing in patients with CD were EBV-positive. Of the EBV-positive lymphomas, three displayed a pattern of EBV latent gene expression consistent with type I latency (EBNA2(-)/LMP1(-)), two a type II pattern (EBNA2(-)/LMP1(+)), and one a type III pattern (EBNA2(+)/LMP1(+)). These findings suggest that EBV infection is involved in the pathogenesis of a proportion of colorectal NHLs developing in IBD. Iatrogenic immunosuppression may contribute to the development of these lymphomas. By contrast, all 17 IBD-associated CRCs were EBV-negative, including a case of CRC occurring synchronously with an EBV-positive NHL. In conjunction with previous reports on sporadic CRCs, this suggests that EBV is not involved in the pathogenesis of CRC.

Adenocarcinoma↗

PubMed1997

Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees.

We have investigated whether there is a locus on chromosome 6 that confers an increased susceptibility to schizophrenia using a two-stage approach and nonparametric linkage analysis. Allele sharing identical by descent (IBD) and multipoint maximum likelihood score (MLS) statistics were employed. Results from two tested data sets, a first data set, or genome scanning data set, and a second replication data set, show excess allele sharing for multiple markers in 6q, a chromosomal region not previously reported as linked to schizophrenia. In our genome scanning data set, excess allele sharing was found for markers on 6q13-q26. The greatest allele sharing was at interval 6q21-q22.3 at marker D6S416 (IBD percentage 69; P = 0.00024). The multipoint MLS values were greater than 2.4 in the 11.4-cM interval delimited by D6S301 and D6S303, with a maximum value of 3.06 close to D6S278 and of 3.05 at D6S454/D6S423. We did not confirm, however, the previously described linkage in 6p, when tested in the systematic genome scanning data set. The replication data set also showed excess allele sharing in chromosomal area 6q13-q26, which overlapped with the aforementioned positive linkage area of the genome scanning data set. The highest sharing of the second data set was at D6S424 (IBD percentage 64; P = 0.0004), D6S283 (IBD percentage 62; P = 0.0009), and D6S423 (IBD percentage 63; P = 0.0009). Multipoint MLS analysis yielded MLS values greater than 1 in an area of about 35 cM, which overlaps with the MLS multipoint area of linkage from the genome scanning data set. The multipoint MLS at the D6S454/D6S423 locus was 2.05. In the second data set, the maximum multipoint MLS was located about 10 cM centromeric from the maximum of the genome scanning data set, at the interval D6S424-D6S275 (2.35). Our results provide very suggestive evidence for a susceptibility locus for schizophrenia in chromosome 6q from two independent data sets.

Alleles↗

PubMed2000

Cd1d-restricted cellular lysis by peripheral blood lymphocytes: relevance to the inflammatory bowel diseases.

The CD1d molecule has been implicated to play a role in inflammatory bowel diseases (IBD), possibly through its presentation of an intestinal antigen trigger. To understand the role of the CD1d class I-like protein in IBD, we investigated the molecule's expression in diseased intestinal tissue and determined its potential to undergo specific recognition by intraepithelial and peripheral blood lymphocytes (PBLs) derived from IBD patients. We have observed an increase in precipitable CD1d in inflamed tissues, which suggests CD1d up-regulation in IBD; this was not accompanied by the occurrence of CD1d-specific cytotoxicity by lymphocytes isolated from the same tissue sites. In contrast, we have observed CD1d-specific cytotoxicity by PBLs from both patients and normal controls mediated by a possibly unique type of lymphocytic cell. These observations support a model in which intestinal inflammation may be initiated by circulating PBLs following the tissue-specific upregulation of CD1d. These activated PBLs may then be the source of the extraintestinal manifestations observed with IBD. We therefore propose that the cells responsible for this activity may play a role in regulating immune responses through the specific recognition of CD1d-specific antigen(s).

Antigens, CD↗

PubMed2006

The B-cell system in inflammatory bowel disease.

Secretory immunity is the best-defined part ot the mucosal immune system. This adaptive humoral defense mechanism depends on a fine-tuned cooperation between secretory epithelia and local plasma cells. Such mucosal immunocytes produce preferentially dimers and larger polymers of immunoglobulin A (collectively called pIgA), which contain J chain and therefore can bind to the epithelial secretory component (SC). This transmembrane glycoprotein functions as pIg receptor (pIgR) that also translocates pentameric IgM to the epithelial surface. B cells with a high level of J-chain expression and pIg-pIgR interactions at mucosal effector sites are thus necessary for the generation of secretory antibodies (SIgA and SIgM). Secretory antibodies perform immune exclusion in a first-line defense, thereby counteracting microbial colonization and mucosal penetration of soluble antigens. However, local production of pIgA is significantly down-regulated in inflammatory bowel disease (IBD), as revealed by strikingly decreased J-chain expression. Although the total increase of the immunocyte population in IBD lesions probably compensates for the relatively reduced pIgA production, decreased pIgR/SC expression in regenerating and dysplastic epithelium signifies that the SIgA system is topically deficient. There is, moreover, a significant shift from IgA2 to IgA1 production, the latter subclass being less resistant to proteolytic degradation. These changes--together with activation of mucosal macrophages and a dramatic increase of IgG-producing cells--may reflect local establishment of a second defense line which, however, is unsuccessful in its attempt to eliminate antigens derived from the indigenous microbial flora. Such a 'frustrated' local humoral immune system results in altered immunological homeostasis and jeopardized mucosal integrity. Complement activation observed in relation to epithelium-bound IgG1 in ulcerative colitis indicates, moreover, that the surface epithelium is subjected to immunological attack by an autoimmune reaction. These luminal deposits regularly contain terminal cytotoxic complement, and often also C3b as a sign of persistent activation. Comparison of identical twins, discordant with regard to ulcerative colitis, suggests that the markedly skewed local IgG1 response seen in this IBD entity may be genetically determined. The initial event(s) eliciting B-cell driven immunopathology in IBD remains unknown. Abrogation of oral tolerance to certain antigens from commensal bacteria has been suggested as a putative early mechanism, and lymphoid neogenesis and hyperplasia in the lesions most likely signify massive microbial overstimulation of the local B-cell system. Such ectopic lymphoid microcompartments may contribute substantially to the proinflammatory systemic-type of B-cell responses occurring in established IBD lesions.

Animals↗

PubMed2006

From immunogenic mechanisms to novel therapeutic approaches in inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are the two most common forms of chronic inflammatory bowel disease (IBD). The etiology of IBD is still unclear and should be considered as multi-factorial according to recent studies. Genetic factors seem to play a pathogenetic role as well as environmental, infectious and immulogical factors. Substantial progress, however, has been made in the understanding of the pathogenesis of IBD during the past years persuing the view, that IBD could result from disturbances of the intestinal barrier and a pathologic activation of the intestinal immune response towards luminal, bacterial antigens. This paradigm has led to the identification of key players of the intestinal immune system, which represent promising targets for novel therapeutic approaches. The objective of this chapter is to provide an overview over recent advances in the elucidation of the intestinal immune system in IBD and novel therapeutic approaches that have been derived from these results. Molecular biological techniques have revealed, that many of the established conventional antiinflammatory drugs such as salicylic acids, steroids or immunuosuppressants act at the same molecules that are the target for modern biologicals, i.e., the cytokine TNF or the transcription factor NFkappaB. This chapter, however, focusses on novel experimental approaches such as recombinant antiinflammatory cytokines, neutralizing antibodies or antisense oligonucleotides.

Animals↗

PubMed1994

Quantification of pulmonary uptake of indium-111 labelled granulocytes in inflammatory bowel disease.

This study describes a method for quantifying the pulmonary trapping of indium-111 labelled polymorphonuclear (PMN) cells in patients with inflammatory bowel disease (IBD) in comparison to non-inflamed controls. Twenty patients with extensive IBD were studied by 111In-PMN scintigraphy. Gamma-camera images were obtained at 2.5-4 h (early) and 20-25 h (late) after the injection of autologous PMNs labelled in plasma with 111In-tropolonate. Local uptake in the chest, iliac bone marrow, spleen and liver was quantified as the counts per pixel per second per MBq of injected 111In for both early and late scans. Fourteen subjects without inflammatory disease were studied as controls. IBD patients showed significantly greater loss of splenic activity between early and late scans compared with controls (mean +/- SD: -35.7% +/- 16.6% versus -4.5% +/- 6.1%, P < 0.001). There was no significant difference between control and IBD groups with respect to liver and bone marrow uptake on both early and late scans. Chest uptake was significantly higher in patients with IBD on both early (6.4 +/- 1.6 cps/MBq/pix) and late (5.6 +/- 1.5 cps/MBq/pix) scans, compared with the controls (4.8 +/- 1.3 cps/MBq/pix, P < 0.005 and 3.4 +/- 1.0 cps/MBq/pix, P < 0.001 respectively). The chest uptake in the control group on the late scans demonstrated a significant linear correlation with iliac uptake (y = 0.23x + 0.41, r = 0.87, n = 14). Assuming in controls that there is no parenchymal uptake of 111In, this regression enables an estimate to be made, based on iliac counts, of the count rate from bone marrow in the chest wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗