PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Colitis, Lymphocytic”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources
PubMed2004

A role for proteinase-activated receptor-1 in inflammatory bowel diseases.

Proteinase-activated receptor-1 (PAR1), a G protein-coupled receptor activated by thrombin, is highly expressed in different cell types of the gastrointestinal tract. The activity of thrombin and of other proteinases is significantly increased in the colon of inflammatory bowel disease (IBD) patients. Since PAR1 activation in tissues other than the gut provoked inflammation, we hypothesized that PAR1 activation in the colon is involved in the pathogenesis of IBD. Here, we demonstrate that PAR1 is overexpressed in the colon of IBD patients. In mice, intracolonic administration of PAR1 agonists led to an inflammatory reaction characterized by edema and granulocyte infiltration. This PAR1 activation-induced inflammation was dependent on B and T lymphocytes. Moreover, PAR1 activation exacerbated and prolonged inflammation in a mouse model of IBD induced by the intracolonic administration of trinitrobenzene sulfonic acid (TNBS), while PAR1 antagonism significantly decreased the mortality and severity of colonic inflammation induced by TNBS and dextran sodium sulfate. In these 2 models, colitis development was strongly attenuated by PAR1 deficiency. Taken together, these results imply an important role for PAR1 in the pathogenesis of experimental colitis, supporting the notion that PAR1 inhibition may be beneficial in the context of IBD and possibly in other chronic intestinal inflammatory disorders.

Adult↗
PubMed2002

IL-10 gene therapy prevents TNBS-induced colitis.

The transfer of genes encoding immunomodulatory proteins to the intestinal mucosa is a promising new approach to the treatment of Crohn's disease (CD). This study investigates the therapeutic efficacy of an adenoviral vector encoding IL-10 (AdvmuIL-10) in experimental colitis. BALB/c mice were treated with a single intravenous injection of AdvmuIL-10, empty cassette virus (Adv0) or PBS prior to the induction of trinitrobenzene sulphonic acid (TNBS) colitis. AdvmuIL-10 treatment prevented the severe loss of body weight associated with TNBS administration. In addition, AdvmuIL-10 therapy led to a significant reduction in both stool markers of inflammation (IL-1beta and TNFR-II) and acute phase response (serum amyloid protein). Finally, the histological scores of mice with TNBS colitis treated with AdvmuIL-10 were significantly lower than Adv0- or PBS-treated controls. The therapeutic efficacy of AdvmuIL-10 was associated with a decrease in the IFN-gamma and IL-6 levels detected in colonic homogenates from mice with TNBS colitis, whereas no effect was observed on cytokine release from stimulated systemic lymphocytes. Thus, AdvmuIL-10 is an effective therapy in the TNBS model of colitis. Gene therapy strategies using adenoviral vectors encoding IL-10 may prove to be a potent therapy for chronic inflammatory conditions such as CD.

Adenoviridae↗
PubMed2006

Histone hyperacetylation is associated with amelioration of experimental colitis in mice.

Inhibitors of histone deacetylases (HDAC) are being studied for their antiproliferative effects in preclinical cancer trials. Recent studies suggest an anti-inflammatory role for this class of compounds. Because inflammatory bowel disease is associated with an increased risk of malignancies, agents with antiproliferative and anti-inflammatory properties would be of therapeutic interest. HDAC inhibitors from various classes were selected and evaluated for their in vitro capacity to suppress cytokine production and to induce apoptosis and histone acetylation. Valproic acid (VPA) and suberyolanilide hydroxamic acid (SAHA) were chosen for further studies in dextran sulfate sodium- and trinitrobenzene sulfonic acid-induced colitis in mice. In vitro, inhibition of HDAC resulted in a dose-dependent suppression of cytokine synthesis and apoptosis induction requiring higher concentrations of HDAC inhibitors for apoptosis induction compared with cytokine inhibition. Oral administration of either VPA or SAHA reduced disease severity in dextran sulfate sodium-induced colitis. The macroscopic and histologic reduction of disease severity was associated with a marked suppression of colonic proinflammatory cytokines. In parallel to the beneficial effect observed, a dose-dependent increase in histone 3 acetylation at the site of inflammation was shown under VPA treatment. Furthermore, SAHA as well as VPA treatment resulted in amelioration of trinitrobenzene sulfonic acid-induced colitis, which was associated with an increase of apoptosis of lamina propria lymphocytes. Inhibitors of HDAC reveal strong protective effects in different models of experimental colitis by inducing apoptosis and suppressing proinflammatory cytokines, thereby representing a promising class of compounds for clinical studies in human inflammatory bowel disease.

Acetylation↗
PubMed2003

Pathology of drug-associated gastrointestinal disease.

A large number of drugs have gastrointestinal side-effects of which diarrhoea or constipation, nausea and vomiting are amongst the commonest. In relatively few are there diagnostic pathological changes and this review draws attention to the most common. Incriminating a drug as a cause of specific pathological changes requires the drug to be associated with the changes, for the latter to resolve when the drug is withdrawn and for them to re-appear when a patient is rechallenged with the drug. Individual histological features such as apoptosis, tissue infiltration by eosinophils and increased intra-epithelial lymphocytes within the gut mucosa can be clues to an iatrogenic aetiology but these are by no means specific. Amongst the few pathognomonic patterns of drug reactions is pseudomembranous colitis and diaphragm disease. These, along with others such as reactive gastritis and the collagenous and lymphocytic forms of microscopic colitis, in which drugs have also been implicated, are described here.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

[Distribution of T cell subsets and DR antigen positive T cells in peripheral blood and in intestinal mucosa of inflammatory bowel disease].

The absolute number of T cell subsets and the rate of T cell DR antigen expression in the peripheral blood and the intestinal mucosa in IBD patients were compared with those in healthy normal controls by two color analysis. The methods used here were flow cytometry for the peripheral blood and immunohistological fluorescent staining for the intestinal mucosa. In peripheral blood lymphocyte (PBL), helper (CD4+ Leu8-) T cells increased in ulcerative colitis (UC), whereas suppressor (CD8+ CD11+) T cells decreased in Crohn's disease (CRD). In lamina propria lymphocyte (LPL) of intestinal mucosa, there were no changes in the proportion of T cell subsets in UC, whereas suppressor (CD8+ CD11+) T cells increased in inflamed mucosa of CRD. DR antigen positive T cells did not increase in PBL, but they increased in LPL of both UC and CRD. In conclusion, there are some differences in distribution of T cell subsets and DR antigen positive T cells between the peripheral blood and the intestinal mucosa in IBD patients. Moreover, the heterogeneity of the distribution of T cell subsets is observed between UC and CRD.

Adolescent↗
PubMed2007

Beta-glucosylceramide: a novel method for enhancement of natural killer T lymphoycte plasticity in murine models of immune-mediated disorders.

BACKGROUND: beta-Glucosylceramide, a naturally occurring glycolipid, exerts modulatory effects on natural killer T (NKT) lymphocytes. AIM: To determine whether beta-glucosylceramide can alter NKT function in opposite directions, colitis was induced by intracolonic installation of trinitrobenzenesulphonic acid, and hepatocellular carcinoma (HCC) was induced by transplantation of Hep3B cells. METHODS: The immunological effect of beta-glucosylceramide was assessed by analysis of intrahepatic and intrasplenic lymphocyte populations, serum cytokines and STAT protein expression. RESULTS: Administration of beta-glucosylceramide led to alleviation of colitis and to suppression of HCC, manifested by improved survival and decreased tumour volume. The beneficial effects were associated with an opposite immunological effect in the two models: the peripheral:intrahepatic CD4:CD8 lymphocyte ratio increased in the colitis model and decreased in the HCC group. The peripheral:intrahepatic NKT lymphocyte ratio decreased in beta-glucosylceramide-treated mice solely in the HCC model. The effect of beta-glucosylceramide was associated with decreased STAT1 and 4 expression, and with overexpression of STAT6, along with decreased interferon gamma levels in the colitis model, whereas an opposite effect was noted in the HCC model. CONCLUSIONS: beta-glucosylceramide alleviates immunologically incongruous disorders and may be associated with "fine tuning" of immune responses, by changes in plasticity of NKT lymphocytes.

Animals↗
PubMed1997

Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice.

The role of antibodies (Abs) in the development of chronic colitis in T cell receptor (TCR)-alpha-/- mice was explored by creating double mutant mice (TCR-alpha-/- x immunoglobulin (Ig)mu-/-), which lack B cells. TCR-alpha-/- x Ig mu-/- mice spontaneously developed colitis at an earlier age, and the colitis was more severe than in TCR-alpha-/- mice. Colitis was induced in recombination-activating gene-1 (RAG-1-/-) mice by the transfer of mesenteric lymph node (MLN) cells from TCR-alpha-/- x Ig mu-/- mice. When purified B cells from TCR-alpha-/- mice were mixed with MLN cells before cell transfer, colitis did not develop in RAG-1-/- mice. Administration of the purified Ig from TCR-alpha-/- mice and a mixture of monoclonal autoAbs reactive with colonic epithelial cells led to attenuation of colitis in TCR-alpha-/- x Ig mu-/- mice. Apoptotic cells were increased in the colon, MLN, and spleen of TCR-alpha-/- x Ig mu-/- mice as compared to Ig mu-/- mice and TCR-alpha-/- mice. Administration of the purified Ig from TCR-alpha-/- mice into TCR-alpha-/- x Ig mu-/- mice led to decrease in the number of apoptotic cells. These findings suggest that although B cells are not required for the initiation of colitis, B cells and Igs (autoAbs) can suppress colitis, presumably by affecting the clearance of apoptotic cells.

Adoptive Transfer↗
PubMed2001

Delivery of glucocorticoid conjugate in rat gastrointestinal tract and its treatment for ulcerative colitis.

AIM: To evaluate colonic delivery and therapeutic effect of the newly synthesized dexamethasone (DX)-dextran (500 000) conjugate (DXD50) in the rat. METHODS: The amount of dexamethasone was measured in the contents from different parts of rat gastrointestinal tract and in plasma after ig conjugate. Therapeutic effect of conjugate and DX was tested in trinitrobenzenesulfonic acid-induced colitis in rat. Repair of colitis was assessed by measuring colonic ulceration area, colon weight, and colonic myeloperoxidase (MPO) activity. Systemic immunosuppression of DX was evaluated with weight of thymus and spleen and lymphocyte count in peripheral blood from rat with ulcerative colitis. RESULTS: Dexamethasone released from conjugate was mainly distributed in contents of cecum and colon. When DXD50 and DX 0.25 micromol . kg-1 . d-1 were used ig to treat ulcerative colitis in rat, the ulcerative area of colon was reduced by 55.6 % and 33.3 %, respectively whereas colon weight was reduced by 17.9 % and 2.6 %, respectively. The conjugate had no effect on lymphocyte count in peripheral blood, spleen weight, and thymus weight of rat which could be reduced markedly by the same dose of DX (P < 0.05 vs control). CONCLUSION: DXD50, which could specifically deliver DX to large intestine, is a promising agent in the treatment of human inflammatory bowel disease.

Animals↗
PubMed1985

Studies on lymphocyte subpopulations in human colonic biopsy specimens by colonoscopy.

Lymphocytes, isolated by the enzymatic technique, from colonic mucosal specimens obtained from eight patients with ulcerative colitis (UC), two with ischemic colitis, two with antibiotic-associated colitis, and 15 controls by colonoscopic biopsy were used to examine T and B cells. In control biopsy specimens, the mononuclear cell yield averaged 3.6 +/- 0.3 (SEM) X 10(6)/g with a viability of 93 +/- 1%, while T and B cells expressed as a percentage of total lymphocyte counts were 65 +/- 1% and 15 +/- 1%, respectively. T and B cells in the ascending, transverse, and sigmoid colon and rectum did not present any differences. In involved tissue at the active stage of UC, the mononuclear cell yield averaged 11.4 +/- 2.1 X 10(6)/g, and T and B cells constituted 49 +/- 3% and 43 +/- 4%, respectively. After treatment for two months with salazosulfapyridine, mononuclear cell yields in five cases of UC were significantly reduced to an average of 3.9 +/- 0.8 X 10(6)/g as compared to the pretreatment level (P less than 0.01). The percentage of T cells was significantly increased from 48 +/- 2% to 62 +/- 2% (P less than 0.01), and that of B cells was significantly reduced from 39 +/- 2% to 27 +/- 3% (P less than 0.01). These results revealed a significant difference in the subpopulations of mucosal lymphocytes in the involved sites in the active stage of UC as compared to normal controls, suggesting that immunological abnormalities may be implicated in the etiology of this disease and that disease remission on salazosulfapyridine treatment is associated with a correction of the colonic lymphocyte abnormalities.

Adult↗
PubMed2006

Synergistic costimulation by both B7 molecules regulates colitis pathogenesis.

It has been reported that B7-1 and B7-2 play different roles in the pathogenesis of autoimmunity, but this issue is controversial. Here we analyzed colitis induced by transfer of CD45RB(high) CD4+ T cells to immune-deficient recipients that lack expression of either B7-1 or B7-2. Surprisingly, disease was greatly accelerated in Rag(-/-) recipients deficient for either B7 molecule. Antigen presenting cells (APCs) lacking B7-1 or B7-2 stimulated T cell proliferation in vitro, but caused suboptimal IL-2 production, leading to decreased induction of CTLA-4. The data suggest that regulatory T cells function relatively normally in B7 single-deficient recipients, but they cannot restrain the increased pathogenesis by naïve cells primed in B7 single-deficient mice. Therefore, the inhibitory effect of CTLA-4 on pathogenic T cells likely slows colitis, even in the absence of regulatory T cells. While a full block of costimulation may prevent autoimmunity, our data indicate, surprisingly, that a partial block may in some cases augment disease.

Antigens, CD↗
PubMed1971

Quantitation of intraepithelial lymphocytes in human jejunum.

An estimate of the number of intraepithelial lymphocytes in jejunal villous epithelium can be obtained by differential counting of nuclei in the epithelium. From counts carried out in 160 jejunal biopsies from patients who did not have coeliac disease the normal range has been established as 6-40 intraepithelial lymphocytes per 100 villous epithelial cells. In some biopsies there was a moderate increase in the intraepithelial lymphocyte count; this was probably an objective measurement of ;increased chronic inflammatory cell infiltrate'. Intraepithelial lymphocyte counts were high in untreated coeliac disease; counts were lower, but rarely within the normal range, in coeliac patients on a gluten-free diet. Counts were normal in most autoimmune diseases, ulcerative colitis, and Crohn's disease. There were abnormal intraepithelial lymphocyte counts in four patients, with otherwise normal jejunal histology, in whom no cause had been found to explain prolonged and incapacitating gastrointestinal symptoms.

Adolescent↗
PubMed1998

Variation in gut-homing CD27-negative lymphocytes in inflammatory colon disease.

Prolonged antigenic stimulation results in lymphocyte shedding of CD27, a member of the tumour necrosis factor receptor (TNFR) family, and transformation to a stable phenotype capable of synthesizing interleukin-4 (IL-4). Co-expression of alpha4beta7 identifies those cells with gut-homing potential. We have investigated these cell populations in patients with inflammatory colonic disease. Circulating and lamina propria mononuclear cells were isolated from patients with Crohn's disease (CD), ulcerative colitis (UC), non-inflammatory bowel disease (non-IBD) colonic inflammation and healthy controls. Double and triple colour flow cytometry for CD3, CD4, CD27, alpha4beta7 and intracellular cytokines was performed. Circulating CD4+ CD27- populations were increased in patients with CD (8.8 +/- 0.8%, P < 0.001), UC (12.2 +/- 1.9%, P < 0.001) and non-IBD colitis (10.5 +/- 1.3%, P < 0.01) as compared with controls (6.1 +/- 0.5%). CD4+ CD27- alpha4beta7+ cells were increased in CD (P < 0.01). Lamina propria CD4+ CD27- populations were depressed significantly in CD (P < 0.05), UC (P < 0.02) and non-IBD colitis (P < 0.03). Mucosal CD4+ CD27- cells synthesized IL-4 in preference to interferon-gamma. Thus, colonic inflammation is associated with alterations in gut-tropic circulating and mucosal populations of differentiated memory T cells with the phenotype of predominantly IL-4-synthesizing cells.

CD4-Positive T-Lymphocytes↗
PubMed1986

Blood transfusion, skin test reactivity, and lymphocytes in inflammatory bowel disease.

Peripheral lymphocytes, T and B cell counts, and skin test reactivity to five recall antigens were determined before operation and 6 to 18 months after operation with or without blood transfusion in 59 patients with inflammatory bowel disease. Significantly reduced preoperative peripheral lymphocyte and T cell counts reached normal levels 6 to 18 months after operation in patients who had not received perioperative blood transfusions. However, lymphocytes and T cells of transfused patients remained decreased, unchanged from preoperative levels, and significantly lower than those of control subjects (p less than 0.005) and levels of patients who had not been transfused (p less than 0.05). Before operation, transfused and untransfused patients were identical in age, Crohn's disease activity index, and peripheral lymphocyte and T and B cell counts. Equal numbers of patients were taking steroids and were anergic to skin tests with five recall antigens. Transfused patients weighed less preoperatively than untransfused patients, and these patients then gained a significant amount of weight. These results suggest that some of the immunologic abnormalities that accompany inflammatory bowel disease may be influenced by blood transfusions.

B-Lymphocytes↗
PubMed2003

Rho GTPase is activated by cytotoxic necrotizing factor 1 in peripheral blood T lymphocytes: potential cytotoxicity for intestinal epithelial cells.

Some strains of Escherichia coli related to acute cystitis or colitis produce a toxin named cytotoxic necrotizing factor 1 (CNF-1). CNF-1 mediates its effects on epithelial cells or phagocytes via the permanent activation of small GTP-binding proteins, caused by the toxin-induced deamidation of Glu(63) of p21 Rho. The behavior of peripheral blood T lymphocytes during the acute phase of bacterial colitis has been poorly investigated. Our study was conducted to test whether (i) peripheral blood T lymphocytes can be activated by CNF-1 and (ii) CNF-1-activated T lymphocytes are cytotoxic against intestinal epithelial cells. Activation of T lymphocytes by CNF-1 was assessed by electrophoresis, flow cytometry, confocal microscopy, and electron microscopy studies. Assays for migration and adherence of CNF-1-treated T lymphocytes were performed in Transwell chambers with T84 intestinal epithelial cells grown on polycarbonate semipermeable filters. CNF-1 induced a decrease in the electrophoretic mobility of the GTP-binding protein Rho in treated T lymphocytes. CNF-1 provoked an increase in the content of actin stress fibers and pseudopodia in T lymphocytes. Several adherence molecules were clustered into cytoplasmic projections in CNF-1-treated T lymphocytes and adherence of such lymphocytes on the basolateral pole of T84 was increased, resulting in cytotoxicity toward epithelial cells. Such enhanced adherence in response to CNF-1 was dependent on p42-44(MAP) kinase activation of T lymphocytes. Taken together, these results suggest that CNF-1, by acting on T lymphocytes, may increase in an important fashion the virulence of certain strains of E. coli against the intestinal epithelia.

Bacterial Toxins↗
PubMed1999

Administration of mAb against alpha E beta 7 prevents and ameliorates immunization-induced colitis in IL-2-/- mice.

We previously demonstrated that 2,4,6-trinitrophenol (TNP)-OVA immunization leads to a transmural colitis in the IL-2-/- mouse that is caused by IL-12-driven CD4+ Th1 T cells and resembles human Crohn's disease. The integrin alpha E beta 7 is highly expressed on colonic intraepithelial lymphocytes and has been suggested to function as a homing or retention molecule for intraepithelial lymphocytes. To evaluate the role of alpha E beta 7 in colitis, we administered a mAb against alpha E beta 7 to IL-2-/- mice that were immunized at the same time with TNP-OVA in CFA. To our surprise, this treatment resulted in a significantly reduced colitis severity score, 0-2 vs 3-4, that was associated with a significant reduction in CD4+ lamina propria lymphocyte subpopulation (p < 0.01). In contrast, the total number of splenic CD4+ T cells of treated animals was significantly elevated compared with that of untreated animals (3.2 +/- 0.6 x 107 vs 1.2 +/- 0.2 x 107; p < 0.05). Similarly, functional studies revealed that IFN-gamma production by lamina propria lymphocytes isolated from IL-2-/- TNP-OVA-immunized mice treated with anti-alpha E beta 7 was significantly lower than in untreated IL-2-/- TNP-OVA-immunized mice. In contrast, IFN-gamma production by splenic cells isolated from treated IL-2-/- TNP-OVA-immunized mice was significantly higher than in untreated mice. Finally, TNP-OVA-immunized IL-2-/- mice that were treated after the colitis had been established also showed a significant decrease in mucosal inflammation after alpha E beta 7 mAb administration. Thus, the above findings demonstrate that the onset and maintenance of inflammatory bowel disease depends on the colonic localization of lamina propria CD4+ lymphocytes expressing alpha E beta 7.

Animals↗