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PubMed1981

Liver abscess complicating Yersinia pseudotuberculosis ileitis.

The occurrence of solitary liver abscess is described in a young farmer with subacute terminal ileitis mimicking Crohn's disease. Serologic tests showed high titers of antibodies for Yersinia pseudotuberculosis. Treatment with troleandomycin was successful. This case report suggests that: (a) Yersinia infection must be systematically searched for in all forms of subacute ileitis; (b) a classically benign Yersinia ileitis may be complicated by liver abscess; (c) antibiotic therapy must be undertaken in Yersinia pseudotuberculosis subacute ileitis to avoid severe infectious complications.

Adult↗
PubMed1982

Campylobacter fetus subspecies jejuni isolated from Syrian hamsters with proliferative ileitis.

Two groups of Syrian hamsters received 3 weeks apart from a commercial supplier became ill and were found to have proliferative ileitis (transmissible ileal hyperplasia). Seventy-five of 200 hamsters from one group and 60 of 200 from another group were evaluated by bacteriological and histopathological techniques. Campylobacter fetus subspecies jejuni was isolated from all hamsters showing clinical signs of proliferative ileitis. The organism was recovered from fecal swabs and the ileum. Many asymptomatic animals had microscopic lesions characteristic of proliferative ileitis, and all except one were culture positive for C fetus subspecies jejuni. A group of 48 hamsters from another commercial source and free of the disease were culture negative for C fetus subspecies jejuni. These animals were inoculated by gavage with one of the following: extract of affected ileum (eight hamsters), 1 X 10(8) viable C fetus subspecies jejuni organisms (28 hamsters), or sterile saline (12 hamsters). Ileal-extract inoculated hamsters were culture positive and five of eight developed clinical signs of ileal hyperplasia. Pure-culture-inoculated hamsters had colonization of the ileum by C fetus subspecies jejuni but did not develop hyperplasia of the ileum. With this data and the tendency of C fetus subspecies jejuni to be associated with clinical enteric disease in a variety of animals and man, we suggest that C fetus subspecies jejuni may have an etiologic role in proliferative ileitis of hamsters. Other synergisms or predisposing factors also may be involved.

Animals↗
PubMed2003

Tuberculous ileitis in a renal transplant recipient with familial Mediterranean fever: Gray-scale and power Doppler sonographic findings.

The ileocecal area is the most common site of involvement of intestinal tuberculosis. We report the case of a 26-year-old renal transplant recipient with familial Mediterranean fever who developed tuberculous ileitis. Gray-scale sonography and CT showed circumferential thickening of the bowel wall and enlargement of the mesenteric lymph nodes. Power Doppler sonography revealed markedly increased vascularity in the wall of the affected ileal segment and in the mesenteric nodes. Some nodes had no flow at the center owing to caseation necrosis, a finding consistent with the diagnosis of tuberculous ileitis. Colonoscopy was performed, and histopathologic examination of biopsy specimens revealed acute inflammatory changes. Cultures of the specimens confirmed the presence of Mycobacterium tuberculosis. We conclude that findings on power Doppler sonography may support a diagnosis of tuberculous ileitis and avoid clinical mismanagement.

Adult↗
PubMed1981

Crohn's ileitis and ileocolitis: a study of the anatomical distribution of recurrence.

The records were reviewed of 56 consecutive patients with Crohn's disease (CD) who had had an ileocolonic anastomosis formed during surgical resection for Crohn's ileitis or ileocolitis. Twenty-seven patients (48%) were found to have radiological, pathological, or surgical evidence of recurrent CD. Of 24 patients with a diagnosis of Crohn's ileitis at initial surgery, 9 were found to have recurrent disease proximal to the anastomotic site. Of 32 patients with ileocolitis, 11 had recurrent disease proximal and distal to the anastomosis. Contrary to many prior reports, recurrent CD is not always located proximally to a surgical anastomosis. The distribution of recurrent CD tends to be a statistically significant function of the initial anatomical location with proximal recurrence found most often in Crohn's ileitis, while proximal and distal recurrence is associated with Crohn's ileocolitis (X2 = 4.5 P less than 0.05).

Adolescent↗
PubMed2003

A novel diamino-pyridine derivative (IS-741) attenuates rat ileitis induced by trinitrobenzene sulfonic acid.

BACKGROUND: The etiology and pathogenesis of inflammatory bowel disease remain unknown. However, neutrophil infiltration into the inflammatory lesion is an important process in inflammatory bowel disease. In this study, we used rat trinitrobenzene sulfonic acid (TNBS) ileitis as a Crohn's disease model, and investigated the effects of oral IS-741 (which inhibits the expression of Mac-1, a cell adhesion molecule) on leukocyte-endothelial interactions. METHODS: Rat ileitis was induced by the intraluminal injection of a TNBS solution (160 mg/kg in 50% ethanol) at a site 10 cm proximal to the ileocecal valve. The rats then received oral IS-741 (50 mg/kg) or saline for 7 days. On the day 8 after the initial administration of IS-741 or saline, we determined the visible damage score, and assessed myeloperoxidase (MPO) activity. Concentrations of cytokines in the ileum, such as interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were assayed by enzyme-linked immunosorbent assay (ELISA). We also investigated the infiltration of polymorphonuclear cells and Mac-1 positive cells by histological examinations. RESULTS: The administration of IS-741 resulted in a significant reduction of the visible damage score, myeloperoxidase (MPO) activity, and mucosal IL-8 levels in the ileum as compared with the saline administration. IS-741 also dramatically reduced the infiltration of polymorphonuclear cells and Mac-1 positive cells into the inflamed lesions. CONCLUSIONS: These results indicate that the oral administration of IS-741 inhibits neutrophil infiltration into inflamed lesions, and is effective for attenuating rat TNBS ileitis. This new anti-inflammatory agent may be beneficial for the treatment of inflammatory bowel disease.

Animals↗
PubMed1999

Mesalamine in the treatment of mild to moderate active Crohn's ileitis: results of a randomized, multicenter trial.

BACKGROUND & AIMS: The efficacy of 5-aminosalicylic acid (mesalamine) in the treatment of flare-ups of Crohn's disease is controversial. In previous studies, different locations and pathological behavior of Crohn's disease could have obscured the efficacy of these drugs that deliver their substance in different intestinal sites. The present study tested two different mesalamine formulations with 6-methylprednisolone in mild to moderate active Crohn's ileitis. METHODS: Ninety-four patients with Crohn's ileitis (Crohn's Disease Activity Index [CDAI], 180-350) were randomly assigned to receive for 12 weeks mesalamine tablets, 4 g (35 patients); mesalamine microgranular preparation, 4 g (28 patients); and 6-methylprednisolone, 40 mg (31 patients). Mesalamine microgranular preparation was a gelatin capsule containing 400 mg of mesalamine microgranules coated with Eudragit S, which has been shown to deliver the drug in the terminal ileum. RESULTS: Patients taking mesalamine tablets experienced a decrease of CDAI median score value of 113.5 (95% confidence interval [CI], 33-149) compared with 123 (95% CI, 77-155) in the mesalamine microgranular group and 154 (95% CI, 99-197) in the 6-methylprednisolone group (P = 0.07 [NS]). Remission at the final visit occurred in 19 of 31 (61%) patients taking steroids compared with 21 of 35 (60%) patients taking mesalamine tablets and 22 of 28 (79%) patients taking microgranular mesalamine (NS). Five patients on steroids were withdrawn because of side effects, and a case of pancreatitis was related to microgranular mesalamine. CONCLUSIONS: Mesalamine in microgranular formulation seems to be equally as effective as a standard dosage of steroids in the treatment of the mild to moderate form of Crohn's ileitis.

Adult↗
PubMed1997

Dietary supplementation of nucleotides and arginine promotes healing of small bowel ulcers in experimental ulcerative ileitis.

We previously showed that intravenous total parenteral nutrition supplemented with nucleosides and nucleotides (NS/NT) promoted ulcer healing in rats with indomethacin-induced ileitis. The present study evaluated whether dietary NT supplementation would similarly affect ulcer healing in this model. Female Lewis rats were randomized into either control or experimental groups receiving yeast RNA containing NT or arginine, glutamine, fish oil, guar gum, or a combination of yeast RNA+arginine diets. Ileitis was induced by two doses of indomethacin (7.5 mg/kg) administered subcutaneously 24 hr apart. Ulcer number and length were determined at 4, 8, and 14 days after induction of ileitis. Ileal villous and crypt length, crypt-villous ratio, and bromodeoxyuridine (BrdU) labeling were studied in the control and yeast RNA-supplemented diet groups. Ileal ulceration was present in all groups at 4 and 8 days and was almost healed by 14 days. Rats receiving yeast RNA, arginine, and yeast RNA + arginine diets showed a significant decrease in ulcer number (56%, 28%, and 34%, respectively) and length (67%, 41%, and 48%, respectively) compared to controls at 8 but not at 4 days. Glutamine, fish oil, and guar gum had no effect on ulcer healing at 4, 8, or 14 days. Among the histological parameters, a significant decrease in crypt length in the yeast RNA-supplemented group at 8 days suggested an acceleration of the healing process and restoration to a near-normal crypt-villous architecture. We conclude that the yeast RNA, arginine, and yeast RNA + arginine diets accelerated ulcer healing, as indicated by decreased ulcer number and length. We postulate that the underlying mechanism(s) contributing to ulcer healing may be related, in part, to increased cell proliferation.

Animal Feed↗
PubMed2000

Characterization of M cell development during indomethacin-induced ileitis in rats.

BACKGROUND: M cells play an important role in the intestinal immune system as they have a high capacity for transcytosis of a wide range of microorganisms and macromolecules. However, little is known about the role of M cells during intestinal inflammation. AIM: We studied M cell development during indomethacin-induced intestinal inflammation in rats. METHODS: Ileitis in rats was induced by two subcutaneous injections with indomethacin (7.5 mg/kg) given 24 h apart. Rats were sacrificed after 14 days and tissue was analysed by fluorescence microscopy and electron microscopy. M cells could be visualized by using the FITC-labelled mAb anti-cytokeratin (CK)-8 (clone 4.1.18), which was recently identified as specific M cell marker in rats. The number of cytokeratin-8 positive M cells was related to the surface of the follicle associated epithelium. For morphological studies, we used both transmission electron microscopy (T.E.M.) and scanning electron microscopy (S.E.M.). RESULTS: In non-inflamed ileum M cells were scarce. Only 4% of the follicle associated epithelium were M cells, whereas an increase of M cells up to 11% was found in inflamed follicle associated epithelium (P < 0.001). The rate of M cell induction depended on the macroscopic degree of inflammation. T.E.M./S.E.M. studies showed that in inflamed tissue most M cells underwent apoptosis with typical morphological signs. In contrast to apoptotic M cells, the neighbouring enterocytes usually appeared intact. The number of mononuclear cells below the follicle associated epithelium was significantly increased. S.E.M. studies revealed that during induced ileitis mononuclear cells migrated from the lamina propria into the gut lumen by passing through apoptotic M cells. CONCLUSIONS: During indomethacin-induced ileitis in rats the increase in M cell number in association with apoptosis of M cells may alter the intestinal barrier function. These observations may play a pivotal role in the pathogenesis of chronic intestinal inflammation, e.g. in inflammatory bowel disease.

Animals↗
PubMed2001

Effect of 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced ileitis on the motor function of non-inflamed rat gastric fundus.

During intestinal inflammation, motility disturbances are not restricted to inflamed regions, but may also occur in remote non-inflamed sites of the gastrointestinal tract. Our aim was to investigate the motor function of the gastric fundus after the induction of terminal ileitis in the rat. Ileal inflammation was induced by intraluminal installation of 2,4,6-trinitrobenzenesulphonic acid (TNBS) into the ileum. Inflammation was assessed both histologically and biochemically. Contractions and relaxations of longitudinal muscle strips from the gastric fundus were studied 36 h and 1 week later. During the acute phase of ileal inflammation (36 h), the non-inflamed stomach was distended. The contractility of longitudinal muscle strips of the gastric fundus was decreased due to a post-receptor defect. In addition, nonadrenergic noncholinergic (NANC) relaxations were inhibited due to neuronal dysfunction. Aortic contractility remained normal and the mere presence of food in the stomach did not account for the disturbed neuromuscular function in the gastric fundus. Ablation of extrinsic primary afferent neurones by capsaicin further impaired gastric fundus contractility. Transection and re-anastomosis of the jejunum reversed the effect of TNBS-induced ileitis on the neuromuscular function of the gastric fundus. One week after TNBS, cholinergic neurotransmission was increased in the gastric fundus. During acute ileitis, smooth muscle cell contractility and inhibitory NANC neurotransmission are inhibited in the non-inflamed gastric fundus. This phenomenon may be mediated by intrinsic connections within the enteric nervous system.

Animals↗
PubMed2001

Murine ileitis after intracellular parasite infection is controlled by TGF-beta-producing intraepithelial lymphocytes.

BACKGROUND & AIMS: Acute inflammatory ileitis occurs in susceptible (C57BL/6) mice after oral infection with Toxoplasma gondii. Overproduction of interferon (IFN)-gamma and synthesis of nitric oxide mediate the inflammation. We evaluated the role of transforming growth factor (TGF)-beta produced by intraepithelial lymphocytes (IELs) in this process. METHODS: We analyzed the histologic and immunologic consequences of adoptive transfer of antigen-primed IELs into susceptible mice treated with anti-TGF-beta before oral challenge with T. gondii cysts. An in vitro coculture of enterocytes and IELs assessed the production of chemokines and cytokines in the presence of anti-TGF-beta. RESULTS: Antigen-primed IELs prevent acute ileitis in susceptible mice that is reversed with anti-TGF-beta. Resistant mice (CBA/J) develop ileitis after treatment with anti-TGF-beta. Antigen-primed IELs can induce systemic immunosuppression as measured by depressed IFN-gamma production. In vitro, primed IELs reduce the production of inflammatory chemokines by infected enterocytes and IFN-gamma by splenocytes. CONCLUSIONS: Regulation of the ileal inflammatory process resulting from T. gondii is dependent on TGF-beta-producing IELs. The IELs are an essential component in gut homeostasis after oral infection with this parasite.

Animals↗
PubMed2005

The role of leukotriene B4 in Clostridium difficile toxin A-induced ileitis in rats.

BACKGROUND & AIMS: Clostridium difficile toxin A is a potent intestinal inflammatory agent that has been shown to act at least partially by neurogenic mechanisms involving activation of the transient receptor potential vanilloid 1 (TRPV1) (capsaicin) receptor. We tested the hypothesis that leukotriene B4 (LTB4) mediates the effects of toxin A via activation of the TRPV1 receptor. METHODS: Isolated rat ileal segments were pretreated with pharmacologic agents before intraluminal injection of toxin A or LTB4. After 3 hours, the treated segments were removed and inflammation was assessed by luminal fluid accumulation, myeloperoxidase activity, and histology. RESULTS: LTB4 caused ileitis similar to that caused by toxin A and antagonism of TRPV1 receptors but not LTB4 receptors inhibited LTB4-induced inflammation. LTB4 also stimulated TRPV1-mediated substance P release and pretreatment with a specific substance P-receptor antagonist blocked LTB4-induced substance P action and ileitis. Inhibition of the LTB4 biosynthetic enzyme 5-lipoxygenase inhibited toxin A-induced increases in ileal LTB4 levels and toxin A- but not LTB4-induced ileitis. CONCLUSIONS: LTB4 mediates the inflammatory effects of toxin A via activation of TRPV1 receptors.

Animals↗
PubMed2006

Critical role of endothelial P-selectin glycoprotein ligand 1 in chronic murine ileitis.

L-selectin ligands might be relevant for inflammatory cell trafficking into the small intestine in a spontaneous model of chronic ileitis (i.e., SAMP1/YitFc mice). Immunoblockade of peripheral node addressin or mucosal addressin cell adhesion molecule 1 failed to ameliorate ileitis, whereas P-selectin glycoprotein ligand 1 (PSGL-1) neutralization attenuated both the adoptively transferred and spontaneous disease. PSGL-1 was detected in venules of mesenteric lymph node and small intestine by immunohistochemistry and confirmed by real-time reverse transcription polymerase chain reaction and flow cytometry. In addition, reconstitution of wild-type mice with PSGL-1(-/-) bone marrow demonstrated that PSGL-1 messenger RNA and PSGL-1 protein expression remained on endothelium, localized within mesenteric lymph node and small intestine. Endothelial PSGL-1 bound P-selectin-IgG and its blockade or genetic deletion altered the recruitment of lymphocytes to the small intestine, as revealed by intravital microscopy and homing studies. Endothelial expression of PSGL-1 adds a new dimension to the various cellular interactions involved in small intestinal recruitment. Thus, the multiple roles of PSGL-1 may explain why targeting this single adhesion molecule results in attenuation of chronic murine ileitis, a disease previously resistant to antiadhesion molecule strategies.

Animals↗
PubMed1993

Is there a role for antibiotics as primary therapy in Crohn's ileitis?

Although their use has been deemed plausible by previous investigators, the role of antibiotics as primary therapy in active Crohn's ileitis is still unclear. Here we detail the response of four patients with active ileitis to ciprofloxacin, a quinolone antibiotic. Each patient had a dramatic improvement in abdominal pain and diarrhea coincident with the institution of ciprofloxacin, despite the absence of any obvious enteric infection. It is uncertain whether ciprofloxacin is treating an undetected pathogen, bacterial overgrowth, an unsuspected microperforation, or even if it is having its effect through a mechanism entirely unrelated to its antimicrobial properties. Our experience suggests that there is a need for a prospective controlled trial of ciprofloxacin or other antibiotics in active Crohn's ileitis.

Adult↗
PubMed2005

Pathologic features and clinical significance of "backwash" ileitis in ulcerative colitis.

Patients with ulcerative colitis (UC) may develop inflammation in the distal ileum thought to be due to "backwash" of cecal contents ("backwash ileitis"). However, a systematic analysis of ileal changes in UC has never been performed, and the prevalence and criteria for "backwash" ileitis have not been defined. The aim of this study was to evaluate the prevalence and spectrum of inflammatory changes in the ileum in patients with UC and to correlate ileal changes with outcome after total proctocolectomy and ileal pouch-anal anastomosis. Routinely processed ileocolonic resection specimens from 200 consecutive patients with clinically and pathologically confirmed UC were evaluated for a wide variety of pathologic features in the ileum and colon. The ileal data were correlated with both the clinical features and the pathologic findings in the colon. Follow-up data were obtained to confirm absence of Crohn's disease and to evaluate outcome of ileo-anal pouches. Overall, 34 of 200 (17%) UC patients had inflammatory changes in the ileum (male/female ratio, 16/18; mean age, 42 years); 32 of 34 (94%) had pancolitis, which was significantly higher than the rate of pancolitis (39%) in patients without ileal disease (N = 166) (P < 0.001), but there were no other differences between patients with or without ileal pathology. In the colon, 22 of 34 (65%) patients had severe activity. Ileal changes included villous atrophy and crypt regeneration without increased inflammation (N = 3), increased neutrophilic and mononuclear inflammation in the lamina propria (N = 6), patchy cryptitis and crypt abscesses (N = 21) and focal superficial surface erosions (N = 4), some with pyloric metaplasia (N = 2 of 4). In general, the severity of ileal changes paralleled the severity of colonic activity. However, 2 of 4 (50%) patients with superficial erosions in the ileum had subtotal or left-sided colitis only, and had only mild colonic activity. Other cases showed only mild to moderate colonic activity and patchy or discontinuous involvement of the distal ileum. Upon follow-up of patients with erosions (mean, 48.5 months; range, 26-102 months), none developed manifestations of Crohn's disease anywhere in the gastrointestinal tract. The presence of inflammatory changes in the ileum had no effect on the prevalence of pouch complications or on the occurrence of dysplasia or cancer. Ileal changes in UC are not uncommon (prevalence, 17%), are generally mild in nature (villous atrophy, increased inflammation, scattered crypt abscesses), and are not associated with an increased rate of ileo-anal pouch complications, dysplasia, or carcinoma. In some cases, our findings are consistent with a backwash etiology. However, rarely, ileal erosions may occur in patients without cecal involvement, which may indicate that other pathogenetic mechanisms should be considered in the etiology of ileitis in UC patients.

Adult↗
PubMed1991

Isolation of an intracellular bacterium from hamsters (Mesocricetus auratus) with proliferative ileitis and reproduction of the disease with a pure culture.

An intracellular bacterium was isolated from hamsters (Mesocricetus auratus) with proliferative ileitis. The organism was isolated in Intestine 407 and GPC-16 cell cultures (incubated in a microaerophilic atmosphere) from isolated and lysed epithelial cells from hamsters with proliferative ileitis. The bacterium measured 1.4 to 1.7 microns in length by 0.26 to 0.34 microns in width, was slightly curved, and had an irregular trilaminar cell wall. Inoculation of hamsters with a cell culture lysate containing the organism or a 0.65-microns-pore-size filtrate of an infected-cell lysate resulted in the typical lesions of proliferative ileitis in approximately 50% of the animals in 28 days. Hamsters inoculated with uninfected cells or a 0.2-microns-pore-size filtrate of an infected-cell lysate remained uninfected. Attempts to propagate the organism on cell-free media have been unsuccessful.

Animals↗
PubMed2006

Contractile activity of lymphatic vessels is altered in the TNBS model of guinea pig ileitis.

The ability of the lymphatic system to actively remove fluid from the interstitium is critical to the resolution of edema. The response of the lymphatics to inflammatory situations is poorly studied, so we examined mesenteric lymphatic contractile activity in the 2,4,6-trinitrobenzenesulfonic acid (TNBS) model of guinea pig ileitis, a well-accepted animal model of intestinal inflammation, by videomicroscopy in vivo and in vitro 1, 3, and 6 days after induction of ileitis. Lymphatic function (diameter, constriction frequency, amplitude of constrictions, and calculated stroke volume and lymph flow rate) of isolated vessels from TNBS-treated guinea pigs were impaired compared with sham-treated controls. The dysfunction was well correlated with the degree of inflammation, with differences reaching significance (P < 0.05) at the highest inflammation-induced damage observed at day 3. In vivo, significantly fewer lymphatics exhibited spontaneous constrictions in TNBS-treated than sham-treated animals. Cyclooxygenase (COX) metabolites were suggested to be involved in this lymphatic dysfunction, since application of nonselective COX inhibitor (10 microM indomethacin) or a combination of COX-1 and COX-2 inhibitors (1 microM SC-560 and 10 microM celecoxib) markedly increased constriction frequency or induced them in lymphatics from TNBS-treated animals in vivo and in vitro. The present results demonstrate that lymphatic contractile function is altered in TNBS-induced ileitis and suggest a role for prostanoids in the lymphatic dysfunction.

Animals↗
PubMed2004

Enteroendocrine cells and 5-HT availability are altered in mucosa of guinea pigs with TNBS ileitis.

Enteroendocrine cells act as sensory transducers, releasing 5-HT and numerous peptides that are involved in regulating motility, secretion, and gut sensation. The action of mucosal 5-HT is terminated by a 5-HT reuptake transporter (SERT). In this study, we examined the hypothesis that ileitis leads to changes in enteroendocrine cell populations and mucosal 5-HT availability. Ileitis was induced in guinea pigs by intraluminal injection of 2,4,6-trinitrobenzenesulfonic acid and experiments were conducted 3, 7, and 14 days after treatment. The number of somatostatin, neurotensin, and 5-HT-immunoreactive cells increased at 3 and 7 days of ileitis, respectively, whereas no significant changes in the numbers of cholecystokinin, glucagon-like peptide-2, glucose-dependent insulinotropic peptide, and peptide YY-immunoreactive cells were observed. Chemical stimulation of the inflamed mucosa with sodium deoxycholic acid significantly increased 5-HT release compared with basal release. Mechanical stimulation of the mucosa potentiated the effect of the chemical stimuli at day 7. Epithelial SERT immunoreactivity was significantly reduced during the time course of inflammation. Thus changes in enteroendocrine cell populations and 5-HT availability could contribute to the altered motility and secretion associated with intestinal inflammation by disrupting mucosal signaling to enteric nerves involved in peristaltic and secretory reflexes.

Animals↗
PubMed2004

Blockade of PSGL-1 attenuates CD14+ monocytic cell recruitment in intestinal mucosa and ameliorates ileitis in SAMP1/Yit mice.

The pathogenesis of Crohn's disease (CD) is not known. However, monocytes and macrophages are thought to play important roles in the development of mucosal inflammation. Therefore, in this study, we examined the role of monocyte-endothelial cell interactions in senescence-accelerated mouse P1 (SAMP1)/Yit mice, a murine model of spontaneous ileitis. Fluorescence-labeled CD14+ monocytic cells isolated from the spleen and mesenteric lymph nodes of AKR/J (control) mice were injected into the tail veins of recipient (AKR/J and SAMP1/Yit) mice, and migration in the postcapillary venules (PCV) of Peyer's patches, submucosal venules, and villus microvessels of the terminal ileum was monitored by using an intravital microscope. Rolling and adhesion of CD14+ monocytic cells in the PCV of Peyer's patches and microvessels of the terminal ileum were increased in SAMP1/Yit mice. An immunohistochemical study showed increased expression of P-selectin glycoprotein-1 (PSGL-1), P-selectin, and vascular cell adhesion molecule-1 in the terminal ileum of SAMP1/Yit mice. Antibodies against these three adhesion molecules significantly inhibited adhesion of CD14+ monocytic cells to the PCV of Peyer's patches and microvessels of the terminal ileum, treatment with an anti-PSGL-1 monoclonal antibody (mAb) showing the strongest suppressive effect. Anti-PSGL-1 mAb also attenuated T cell adhesion in microvessels of intestinal mucosa. In addition, periodical administration of an anti-PSGL-1 mAb for 7 weeks significantly ameliorated ileitis of SAMP1/Yit mice. The results suggest that PSGL-1-P-selectin interaction plays an important role in monocyte-endothelial cell interactions and the development of ileitis in a murine model of CD and that the blockade of this adhesion molecule may be a novel strategy for treating CD.

Animals↗