Hemodynamics in the colonic mucosa of rats with dextran sulfate-induced colitis in the early phase

We investigated hemodynamics in the colonic mucosa of rats with experimental colitis induced by the administration of dextran sulfate sodium (DSS). As parameters of hemodynamics, we determined the indices of mucosal hemoglobin concentration (IHb) and mucosal oxygen saturation (ISO₂), measured by reflectance spectrophotometry, and an index of colonic mucosal blood flow (Flow), measured by laser-Doppler flowmetry. In the ascending colon, each parameter was measured by a combination of these methods after 1, 3, 5, 7, and 10 days of DSS administration. Histopathological examination was also performed. IHb in the DSS group increased with time; on the 7th day, the value was 126.9±8.32, while that in the control group was 85.0±4.14, IHb in the DSS group being significantly increased (P<0.02). ISO₂ in the DSS group was lower than that in the control group, and on the 7th day, was significantly lower in the DSS group (25.7±1.34) than in the control group (33.4±1.77) (P<0.01). No changes in Flow were observed in either the DSS or the control group during the administration period, and no significant difference in Flow was found between the two groups. On histopathological examination, we observed a time-dependent increase in the infiltration of inflammatory cells in the ascending colon of rats treated with DSS, but changes such as erosion and ulceration were not found in the superficial layer of the mucosa. No histopathological changes were found in the control animals. In the early phase of the experimental colitis, hemodynamic alterations in the colonic mucosa were already present at the time the slight histopathological changes developed. These observations seemed to indicate the involvement of hemodynamic alterations in the subsequent tissue injury.     

Rectal mucosal hemodynamics, evaluated by reflectance spectrophotometry, in patients with chronic hepatitis

To evaluate rectal mucosal hemodynamics in patients with chronic hepatitis, we employed reflectance spectrophotometry and examined the results in relation to the presence and severity of chronic hepatitis. Twenty-six patients with histologically diagnosed chronic hepatitis and 21 controls were examined for rectal vascular findings by endoscopy. Indices (I) of rectal mucosal oxygen saturation (ISO₂) and rectal mucosal hemoglobin (IHb) concentration were measured. To minimize the effects of systemic anemia, the IHb was divided by blood Hb concentration, giving the rectal index for Hb (RHb). The relationship between rectal mucosal hemodynamics and the histological grade of chronic hepatitis was studied. Rectal vascular lesions were observed in three patients with chronic hepatitis (11.5%). The RHb in patients with chronic hepatitis was significantly higher than that in the controls (5.74 ± 0.71 and 4.82 ± 1.12, respectively; P < 0.01). There was no significant difference in ISO₂ levels (44.23 ± 5.84 and 41.94 ± 4.91, respectively). No significant correlation was observed between rectal mucosal hemodynamics and the histological severity of chronic hepatitis, although rectal mucosal hemodynamics changed in patients with chronic hepatitis. Early vascular changes were observed in the rectal mucosa of patients with chronic hepatitis. (Received Oct. 23, 1997; accepted Dec. 19, 1997)     

Somatostatin reduces gastric mucosal blood flow in patients with portal hypertensive gastropathy

Agents which decrease gastric mucosal blood flow (GMBF) are postulated to have beneficial effects in arresting gastrointestinal bleeding in cirrhotic patients with portal hypertension. Our objective was to test the hypothesis that in a dose that significantly lowers wedged hepatic venous pressure (WHVP), a bolus injection of somatostatin will significantly decrease GMBF in patients with portal hypertensive gastropathy (PHG). In this placebo-controlled, double-blind, crossover study, 20 cirrhotic patients with PHG were randomly assigned to receive either somatostatin followed by placebo (Group A) or placebo followed by somatostatin (Group B). Wedged hepatic venous pressure was monitored. GMBF in the antrum and corpus was assessed by reflectance spectrophotometry. Indices of hemoglobin concentration (IHb) and indices of oxygen content (ISO₂) were recorded. Nine patients were assigned to Group A, and 11 to Group B. Mild PHG was seen in 16 patients, and severe PHG in 4 patients. Baseline WHVP, IHb, and ISO₂ were similar in both treatment groups. Wedged hepatic venous pressure (WHVP) was significantly lowered [median, 17.6%; interquartile range (–27.0, –12.6%); P=0.0008] after a 250-µg bolus injection of somatostatin. This dose of somatostatin significantly reduced IHb both in the antrum [–10.2% (–23.4, 0.4%)] and in the corpus [–5.8% (–16.6, 5.6%)] compared to placebo (P=0.02 and 0.04, respectively). Intravenous bolus injection of 250 µg somatostatin significantly reduces WHVP and GMBF in patients with PHG. Whether this ability to decrease the GMBF in PHG makes somatostatin an effective treatment in acute gastrointestinal bleeding in PHG deserves to be studied.     

Influence of nitroglycerin on portal pressure and gastric mucosal hemodynamics in patients with cirrhosis

We studied 30 patients with cirrhosis to determine the effect of nitroglycerin on portal and gastric mucosal hemodynamics. Systemic hemodynamics, portal venous pressure (PVP), the hemoglobin index (IHB), and the oxygen saturation index (ISO₂) of the gastric mucosa were measured before and after a continuous infusion of nitroglycerin. The patients were divided into two groups according to the presence or absence of major portal-systemic collateral routes on portograms. Nitroglycerin caused a reduction in PVP in all patients. Although there was no significant difference in systemic hemodynamic changes between the two groups, the reduction in PVP in patients with major portal-systemic collaterals was significantly higher than in those without major collaterals. A nitroglycerin infusion, at a dose of 1.0μg/kg per min for 10 min, produced a reduction in both IHB (?16%,P<0.001) and ISO₂ (?13%,P<0.001) in the gastric mucosa, indicating gastric mucosal ischemia secondary to splanchnic vasoconstriction. These findings suggest that the continuous infusion of nitroglycerin reduces PVP in cirrhotic patients, particularly in those with major portal-systemic collaterals, and reduces the congestion of the gastric mucosa in patients with portal hypertension.     

MAGNIFYING COLONOSCOPIC FINDINGS BY ADAPTED INDEX OF HEMOGLOBIN ENHANCEMENT IMAGE PROCESSING SYSTEM IN ULCERATIVE COLITIS

In order to elucidate whether the adapted index of hemoglobin (IHb) enhancement image processing system is useful in the evaluation of ulcerative colitis, we retrospectively compared the conventional and adapted IHb processed images in a total of 109 images. These were composed of 49 conventional and 60 magnifying images in 26 patients with ulcerative colitis (UC). Using the adapted IHb enhancement image processing system, 15 of 26 cases (55 of 109 images) were judged as ‘informative’ and the others (11 of 26 cases; 54 of 109 images) were judged as ‘not informative’. On further analysis, almost all the images judged as ‘informative’ by adapted IHb enhancement enabled the easily detection of the enhanced capillary or transparencies of submucosal vessels with the combination use of magnifying colonoscopy. The major reason an image was judged as ‘not informative’ were too much halation, too much contrast and no differences between processed images and the original ones. Further prospective analysis will be required in the evaluation of adapted IHb color enhancement image processing system in the evaluation of UC.     

INFLUENCE OF TOPICAL EPINEPHRINE APPLICATION ON MICROCIRCULATORY DISTURBANCE IN SUBJECTS WITH ULCERATIVE COLITIS EVALUATED BY LASER DOPPLER FLOWMETRY AND TRANSMISSION ELECTRON MICROSCOPY

Background : The aim of this study was to evaluate the state of local microcirculation in ulcerative colitis. Methods : Rectal blood flow was measured in 26 subjects with ulcerative colitis and in 10 normal subjects by laser Doppler flowmetry before and after topical spray of epinephrine during colonoscopy. Of those subjects, mucosal capillaries were observed by transmission electron microscopy in eight subjects with ulcerative colitis and in four normal subjects. Results : The blood flow was significantly higher in subjects with active ulcerative colitis than in normal subjects or in subjects with inactive ulcerative colitis, with the difference being significantly different in subjects with ulcerative colitis and in normal subjects following topical epinephrine spray. The capillaries were almost devoid of erythrocytes in subjects with active ulcerative colitis and the frequency of capillaries with erythrocytes in subjects with active ulcerative colitis before and after epinephrine application did not differ. Conclusions : These results indicate that the mucosal microcirculation in subjects with active ulcerative colitis showed ischemia and functional disorder. Further, continuous measurement of blood flow in subjects with active ulcerative colitis may be a useful method for evaluating the changes in microcirculation.     

Superior mesenteric artery is more important than inferior mesenteric artery in maintaining colonic mucosal perfusion and integrity in rats

Mucosal hemodynamics (by reflectance spectrophotometry) and mucosal damage (by histologic examination) following acute colonic ischemia were evaluated in different anatomic locations in the colon of anesthetized rats. The reflectance spectrophotometer provides an index of mucosal hemoglobin concentration (IHB) and an index of oxygen saturation of hemoglobin (ISO₂). The patterns of ischemia without congestion (IHB, ISO₂) during superior mesenteric artery occlusion, and ischemia with congestion (IHB, ISO₂) during portal vein occlusion, previously demonstrated in the stomach and duodenum, are also applicable to the colon. The significant linear correlations between changes (as percent of baseline) in IHB, ISO₂, and hydrogen gas clearance suggest that changes in these indices are adequate indicators of changes in colonic mucosal perfusion. Superior mesenteric artery ligation produced significant reductions in both indices, and an increase in damage in the mucosa of the cecum, transverse colon, splenic flexure, and left colon, but not the rectum. Inferior mesenteric artery ligation produced only slight reduction in these indices and minimal damage only in the mucosa of the splenic flexure. These results support the hypothesis that the superior mesenteric artery is more important than the inferior mesenteric artery in maintaining colonic perfusion and colonic mucosal integrity in the rat.Supported by the American Society for Gastrointestinal Endoscopy Career Development Award (H850208, H870212), Veterans Administration Medical Research Funds; and in part by research grants (0162-01, 0162-02; 0291-01) from the Smokeless Tobacco Research Council, Inc.; and by funds provided by the Cigarette and Tobacco Surtax Fund of the State of California through the Tobacco Related Disease Research Program of the University of California.     

Plasma interleukin-18 reflects severity of ulcerative colitis

AIM: The aim of this study was to evaluate the association between ulcerative colitis activity and plasma or mucosal concentrations of interleukin (IL)-18. METHODS: 11-18 concentrations were measured in plasma and mucosal samples from 15 patients with active ulcerative colitis (UC). RESULTS: The mean plasma concentration of IL-18 measured in all patients (422±88 pg/mL) doubled the mean value in healthy controls (206±32 pg/mL); however, the difference was not statistically significant. Plasma IL-18 levels revealed a significant positive correlation with scored endoscopic degree of mucosal injury, disease activity index, clinical activity index and C-reactive protein concentration. The mean concentration of plasma IL-18 was significantly higher in patients with severe ulcerative colitis (535±115 pg/mL) than in patients with mild ulcerative colitis (195±41 pg/mL), and in healthy controls. Although the mucosal mean IL-18 concentration in severe ulcerative colitis (2 523±618 pg/mg protein) doubled values observed in mild one (1347±308 pg/mg protein), there was no statistically significant difference. CONCLUSION: Plasma IL-18 can be considered as a surrogate marker helpful in evaluation of ulcerative colitis activity.     

Increased gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy.

To characterize gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy, 34 cirrhotics with this lesion and 24 noncirrhotics were studied by reflectance spectrophotometry and laser-Doppler flowmetry during endoscopy. A significant correlation was observed between the hemoglobin content of the gastric mucosa, measured by reflectance spectrophotometry, and the serum hemoglobin concentration both in cirrhotics (r = 0.72) and in noncirrhotics (r = 0.87). IHb ratio (hemoglobin content of gastric mucosa divided by blood hemoglobin concentration) was higher in cirrhotics with portal hypertensive gastropathy than in noncirrhotics (P < 0.001), whereas the oxygen content of the gastric mucosa was similar in both groups. This pattern indicates that cirrhotics with portal hypertensive gastropathy have increased gastric perfusion without congestion. Gastric blood flow estimated by laser-Doppler was significantly higher in cirrhotics with portal hypertensive gastropathy than in noncirrhotics (P < 0.001). In cirrhotic patients, gastric areas with cherry red spots showed a significantly higher IHb ratio than areas with a mosaic or scarlatina pattern (P < 0.05). The magnitude of changes in gastric perfusion and the endoscopic severity of portal hypertensive gastropathy had no relationship with the degree of portal hypertension or the azygos blood flow.     

Studies of lactic dehydrogenase content in rectal mucosal biopsies

The total lactic dehydrogenase (LD) content and LD isoenzyme ratios were studied in homogenized rectal mucosa from 31 patients with established non-specific mucosal ulcerative colitis and from 16 normal subjects. The total LD content was found to be significantly increased in patients with active ulcerative colitis when compared with patients with inactive colitis or with normal subjects. There was a similar though not a significant increase in the slow moving isoenzymes of LD in samples of rectal mucosa from patients with active colitis. The LD isoenzyme pattern was in the normal range in two of the three patients with histological premalignant changes in rectal biopsy specimens.There was a statistically significant linear correlation between the total lactic dehydrogenase content of rectal mucosa and the carcino-embryonic antigen levels in whole serum.Both the total content and isoenzyme ratios of LD were increased in neoplastic tissue obtained from patients with carcinoma of the colon and with tissue from benign rectal polyps.     

Phenotypes and spontaneous immunoglobulin production in mononuclear cells suspensions isolated from colonic biopsies of patients with mild active and quiescent ulcerative colitis

Lamina propria mononuclear cells can be isolated from mucosal specimens of human colon. In the present study, we have explored whether both the phenotypes and functional properties can be studied in lamina propria mononuclear cell suspensions isolated from the same set of endoscopic biopsies in patients with ulcerative colitis. The counts of CD11b+ lamina propria mononuclear cells in mild active ulcerative colitis were significantly higher than those of both quiescent ulcerative colitis and controls. Similarly, the CD16+ and the CD19+ lamina propria mononuclear cells were significantly increased in mild ulcerative colitis patients in comparison to both quiescent ulcerative colitis and control lamina propria mononuclear cells. Lamina propria mononuclear cells from all the biopsy samples appeared to produce detectable amounts of immunoglobulins of the three classes. The production of IgG in mild ulcerative colitis cultures was significantly higher than that observed in quiescent ulcerative colitis and controls. In contrast, the production of IgA in active ulcerative colitis lamina propria mononuclear cell cultures appeared to be significantly lower than that of both quiescent ulcerative colitis and controls. This study shows that morphology, phenotypes, and functional properties can be assessed in lamina propria mononuclear cell suspensions obtained from the same set of endoscopic biopsy samples. We have also shown that changes in phenotypes and functional status of lamina propria mononuclear cells occurred in mild active ulcerative colitis while no significant abnormality of these parameters was found in quiescent ulcerative colitis. This indicates that a normalization of mucosal immune functions occurs in ulcerative colitis patients when complete clinical and histological remission is achieved.     

Anorectal manometry in active and quiescent ulcerative colitis

Anorectal function was measured in 11 patients with active medically intractable ulcerative colitis, seven patients with quiescent ulcerative colitis, and 18 healthy subjects. The anal resting pressure, squeeze pressure, and ability to defecate a balloon were similar in all groups. Significantly lower rectal distention volumes were required for rectal sensation, critical volume, and to induce rectal contractility in patients with active disease compared to controls or patients with quiescent disease. Rectal compliance was significantly reduced in patients with active and quiescent disease. The increased rectal sensitivity and contractility in patients with active colitis appear to be related to active mucosal inflammation and ulceration. Episodes of mucosal inflammation may be responsible for chronic changes in the rectal wall resulting in fibrosis and decreased compliance in patients with quiescent disease. The frequency and urgency of defecation and the fecal incontinence may be due to a hypersensitive, hyperactive, and poorly compliant rectum.     

Mucosal cell proliferation of the rectal stump in ulcerative colitis patients after ileorectal anastomosis

The proliferative activity and polyamine levels of the rectal epithelium in unoperated ulcerative colitis patients and in ulcerative colitis patients after total colectomy and ileorectal anastomosis were determined and compared with control subjects. Cell proliferation was evaluated in rectal biopsies by in vitro 3H thymidine incorporation by measuring the labeling index and the position of labeled cells along the crypt; polyamines were determined with a chromatographic method. In ulcerative colitis patients the labeling index was significantly increased, and labeled cells were shifted toward the upper part of the crypt when compared with controls. Ileorectal anastomosis patients showed a normalization of the labeling index and a distribution of labeled cells similar to controls. Polyamine levels were also increased in ulcerative colitis patients; in ileorectal anastomosis patients, the level of polyamines was decreased in respect to unoperated patients and return to normal values except for spermine. Because the increased proliferation and higher polyamine levels are related to increased colon cancer risk, our results confirm that ulcerative colitis is a risk factor for the development of carcinoma. Ileorectal anastomosis may reduce this risk through a normalization of mucosal cell proliferative activity and of some polyamine levels.     

Fibrinolytic Activity in the Normal and Inflamed Rectal Mucosa

In an attempt to determine whether an abnormal hemostatic mechanism may account for mucosal friability in active ulcerative colitis, rectal biopsy specimens from normal subjects and from patients with ulcerative colitis, or other inflammatory or radiation-induced disorders of the colon, were studied for fibrinolytic activity by the histochemical fibrin slide technique. Fibrinolytically active sites occurred more frequently in specimens from patients with active ulcerative colitis than in normal specimens. Plasminogen activator was present at sites in the edematous lamina propria.     

Increased Nitric Oxide Production and Inducible Nitric Oxide Synthase Activity in Colonic Mucosa of Patients with Active Ulcerative Colitis and Crohn's Disease

It is postulated that an enhanced production ofnitric oxide by inflamed intestine plays a role in thepathophysiology of active inflammatory bowel disease. Inthis study, systemic NO_x concentrations and colonic nitric oxide synthase activity weredetermined in patients with ulcerative colitis orCrohn's disease. The relationship between these twoparameters and disease activity, as well as differences in nitric oxide synthase activity betweenulcerative colitis and Crohn's disease, were areas ofspecific focus. Patients with active ulcerative colitisand Crohn's disease had significantly elevated plasma NO_x concentrations; a positivecorrelation was found between NO_x values andinducible nitric oxide synthase activities in the activemucosa of these patients. In active ulcerative colitis,levels of inducible nitric oxide synthase were significantlyelevated in both normal and inflamed mucosa, althoughinducible nitric oxide synthase activity was higher inthe latter. These colonic inducible nitric oxidesynthase activities correlated well with the results ofendoscopic and histologic grading of inflammation. Therewas no increase in constitutive nitric oxide synthaseactivity in patients with active ulcerative colitis. However, constitutive nitric oxidesynthase activity was significantly increased in theinflamed mucosa in patients with Crohn's disease. InCrohn's disease, elevated inducible nitric oxidesynthase activity was found in both normal and inflamedmucosa, with no significant difference between thetissues. Such differences in nitric oxide production inthe colonic mucosa possibly reflect the significant differences in the pathophysiology andcharacteristic clinical features between ulcerativecolitis and Crohn's disease.     

Intraluminal excretion of PAF,lysoPAF, and acetylhydrolase in patients with ulcerative colitis

PAF-acether (PAF) is a phospholipid synthesized by numerous inflammatory cells. PAF can produce several pathological changes in various organs, especially in the colon. In animals PAF causes colonic ulceration and inflammation, which are similar to the anatomic lesions seen in human ulcerative colitis. The aim of this study was to measurein vivo colonic production of PAF in active ulcerative colitis using a modified colonic perfusion method. Ten patients with active ulcerative colitis and six control patients were investigated. A colonic segment was continuously perfused with a buffer and the liquid was recovered 20 cm distally, after a 45-min period of equilibration, at 20-min intervals. PAF, lysoPAF, and acetylhydrolase were measured in the colonic samples. PAF and lysoPAF outputs were significantly higher in patients with active ulcerative colitis compared to controls patients. There was a significant correlation between colonic PAF output and, respectively, macroscopic mucosal lesions and myeloperoxidase colonic output. We thus conclude: (1) the colonic perfusion method allowsin vivo study of the metabolism of PAF during ulcerative colitis and could also be used to study the efficiency of PAF antagonists in UC; and (2) colonic production of PAF is increased during ulcerative colitis and correlated to local injury and inflammation. Whether or not PAF plays a role in the pathogenesis of ulcerative colitis remains open for further investigations.     

Increased production of vascular endothelial growth factor by intestinal mucosa of patients with inflammatory bowel disease.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Recent studies have shown significantly increased VEGF serum levels in patients with active Crohn's disease and ulcerative colitis. The origin of the circulating VEGF is not yet completely described. The present investigation examines the VEGF production of colonic mucosa in consideration of mucosal disease activity in patients with inflammatory bowel disease. METHODOLOGY: Fifteen patients with inflammatory bowel disease were studied, 9 patients with Crohn's disease and 6 patients with ulcerative colitis. Biopsies were taken from endoscopically inflamed and non-inflamed colonic mucosa. Therefore, an analysis of the spontaneous VEGF production of cultured biopsies without stimulus and of the histological grade of inflammation scored on a scale of 0-3 (normal mucosa--severe chronic colitis) were performed. Eight patients with irritable bowel syndrome served as controls. VEGF levels in the supernatant of cultured mucosal biopsies were measured using an enzyme linked immunosorbent assay. RESULTS: VEGF production is expressed as pg/mg wet weight of the biopsies. Inflamed mucosa of patients with active ulcerative colitis (16.27 +/- 10.39, p = 0.003, n = 6) and active Crohn's disease (9.88 +/- 5.98, p < 0.012, n = 9) showed a significantly higher spontaneous production of VEGF by colonic mucosa than normal mucosa of controls (3.16 +/- 1.63, n = 8). In addition, there was an increased unstimulated VEGF production by cultured inflamed mucosa of patients with Crohn's disease compared with non-inflamed mucosa (3.88 +/- 3.66, p < 0.015, n = 9). In both Crohn's disease and ulcerative colitis, there was no significant difference between VEGF production by non-inflamed mucosa and normal mucosa of controls. CONCLUSIONS: The present study identifies the intestinal mucosa as one of the origins of the elevated VEGF serum levels in patients with active inflammatory bowel disease and verifies the findings of recent studies about the importance of VEGF in Crohn's disease and ulcerative colitis.     

Reduction in index of oxygen saturation at margin of active duodenal ulcers may lead to slow healing

This study tested the hypothesis that reduced perfusion of a duodenal ulcer margin (ie, the mucosa 1–2 mm from the edge of the ulcer base) is associated with slow healing. Reflectance spectrophotometric measurement of indices of mucosal hemoglobin concentration (IHB) and mucosal hemoglobin oxygen saturation (ISO₂) were obtained endoscopically in 21 patients at the ulcer margin and the adjacent mucosa (ie, the mucosa 1–2 cm from the edge of the ulcer base). In 17 patients with adequate follow-up, stepwise multilinear regression analysis revealed a significantly negative correlation (r=s-0.69, P < 0.05) between ISO₂ at the ulcer margin minus ISO₂ at the adjacent mucosa (ISO)₂ and ulcer healing time. In addition, smoking, being black, and early relapse since the last ulcer attack were found to be associated with increased duration required for healing. The results of this pilot study suggest factors, in addition to smoking, that may have to be considered in future studies concerned with duodenal ulcer healing.This work was supported by the National Institute of Arthritis and Metabolism and Digestive Diseases Grant AM34840, American Society for Gastrointestinal Endoscopy Career Development Award H850208, Veterans Administration Medical Research Funds, and UCLA Academic Senate Grant 4063.     

Immunohistochemical localization of vascular endothelial growth factor in colonic mucosa of patients with inflammatory bowel disease

BACKGROUND/AIMS: Significantly enhanced serum levels of VEGF (vascular endothelial growth factor) were found in patients with inflammatory bowel disease. Peripheral blood mononuclear cells have been identified as one of the origins of the circulating VEGF. The present investigation examines the localization of VEGF at the site of inflammation in colonic mucosa of patients with Crohn's disease and ulcerative colitis. METHODOLOGY: Immunohistochemical localization of VEGF and immunostaining for leukocytes were performed in colonic mucosal biopsies of 41 patients with Crohn's disease, 26 patients with ulcerative colitis and normal mucosal specimens of 5 patients with irritable bowel syndrome. Measurement of immunohistochemical staining for VEGF and for leukocytes within the epithelium and the lamina propria was performed separately by area morphometry using a computerized cell analysis system. RESULTS: In both patients with Crohn's disease and ulcerative colitis immunohistochemical staining for VEGF within the lamina propria of inflamed colonic mucosa was significantly higher compared with noninflamed mucosa (Crohn's disease: 4.26% vs. 0.07%, P < 0.001; ulcerative colitis: 3.68% vs. 0.32%, P = 0.001). There was a significant correlation between immunostaining for leukocytes and VEGF within the lamina propria in both patients with Crohn's disease (r = 0.73, P < 0.05)) and ulcerative colitis (r = 0.67, P < 0.05). In Crohn's disease immunostaining for VEGF within the epithelium was significantly higher in inflamed mucosa compared with noninflamed mucosa (9.85% vs. 0.63%, P < 0.001). In contrast, strong immunostaining for VEGF has been observed in the epithelium of noninflamed mucosa (7.60%, P < 0.003), as well as in inflamed mucosa of patients with active ulcerative colitis (9.68%, P < 0.002) compared with noninflamed mucosa of patients with inactive ulcerative colitis (1.39%). CONCLUSIONS: The present data indicate, that the increased VEGF expression within the epithelium and the interstitial accumulation of VEGF-producing leukocytes in inflamed mucosa may play an important role in the inflammatory mechanisms of Crohn's disease and ulcerative colitis.