溃疡性结肠炎患者基质金属蛋白酶-2,9和抑制因子-1,2的表达及其意义

目的　在转录和蛋白水平检测基质金属蛋白酶 (MMP) 2 ,9和特异性组织抑制因子(TIMP) 1,2在溃疡性结肠炎 (UC)患者和正常志愿者肠粘膜中的表达情况及活性变化。方法　对病理证实的 2 2例UC和 2 0名健康志愿者在内窥镜下取活检 ,采用NorthernBlot和WesternBlot法分别对MMP 2 ,9及TIMP 1,2进行检测 ,并采用明胶酶谱法测定MMP 2 ,9活性。结果　MMP 2 ,9和TIMP 1在正常肠粘膜中均呈现低表达 ,在患者肠粘膜中表达显著升高 (P <0 .0 1) ,而TIMP 2在两种粘膜中的表达量无明显差别。明胶酶谱结果显示MMP 2 ,9在后者中的活性较前者中显著升高 (P <0 .0 5 ) ,且与炎症程度相关。结论　MMP 2 ,9在UC肠炎肠粘膜上皮重塑过程中具有重要作用 ,在疾病的发生和发展中可能起到促进作用     

Evaluation of the Role of Neutrophils in the Pathogenesis of Acetic Acid-Induced Colitis in Mice

Background: Neutrophils are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease, since prominent neutrophil infiltration has been observed in the inflamed colonic mucosa of patients with IBD. However, the role of neutrophils in the pathogenesis of IBD and experimental colitis remains equivocal. The aim of the present study is to clarify the possible role of neutrophils in the progression of acetic acid-induced colitis in mice. Methods: Using neutropenic mice treated with cyclophosphamide or with an LTB₄ receptor antagonist, ONO-4057, the relationship between the severity of macroscopic colonic damage, the extent of myeloperoxidase (MPO) activities in the colonic tissues, and the number of neutrophils in the blood were examined after induction of colitis in mice. Results: Changes of MPO activity in the colonic tissues paralleled well with the severity of the mucosal damage. In spite of a significant reduction in the number of neutrophils in the blood in cyclophosphamide-treated mice, neither the severity of mucosal damage in the colon nor the increase in MPO activities in the colonic tissues was affected 24 h after induction of colitis. Treatment with ONO-4057 significantly suppressed both the severity of mucosal damage in the colon and MPO activities in the colonic tissues in acetic acid-induced colitis in mice. Conclusions: The present results, obtained using treatment with cyclophosphamide and ONO-4057, show that the severity or the progression of acetic acid-induced colitis in mice was not influenced by a reduction of circulating neutrophils to about 25% of base line.     

Impaired Synthesis or Cellular Storage of Norepinephrine, Dopamine, and 5-Hydroxytryptamine in Human Inflammatory Bowel Disease

The present study was aimed at evaluating the extent of dysfunction of the enteroendocrine and enteric nervous system, as indicated by changes in tissue levels of monoamines (dopamine, DA; norepinephrine, NE; 5-hydroxytryptamine, 5-HT) and their precursors and metabolites in the colonic mucosa of patients afflicted with ulcerative colitis (UC, N = 21) and Crohn's disease (CD, N = 22). In CD, but not in UC, NE tissue levels in both the noninflamed and inflamed colonic mucosa were markedly lower than in control subjects (N = 16). In the inflamed mucosa of CD and in UC patients levels of l-DOPA were twice those in controls. DA levels in the inflamed mucosa of CD and UC patients were markedly lower than in controls. This resulted in significant reductions in DA/l-DOPA tissue ratios, a rough measure of l-amino acid decarboxylase activity. 5-HT levels in the inflamed mucosa of CD and UC patients were markedly lower than in controls. In conclusion, intestinal cellular structures responsible for the synthesis and storage of DA, NE, and 5-HT may have been affected by the associated inflammatory process in both CD and UC.     

The ICE Inhibitor Pralnacasan Prevents DSS-Induced Colitis in C57BL/6 Mice and Suppresses IP-10 mRNA but Not TNF-α mRNA Expression

Previously we demonstrated an ameliorating effect of the interleukin-1beta converting enzyme (ICE) inhibitor pralnacasan on dextran sulfate sodium (DSS)-induced colitis. This study investigates the effects of pralnacasan on cytokine expression in DSS-induced colitis. Colitis was induced by oral administration of DSS. Mice were treated intraperitoneally with the ICE inhibitor pralnacasan (50 mg/kg body weight twice daily). Body weight as well as the presence of occult blood or diarrhea was monitored daily. Subgroups were sacrificed at days 4, 8, and 11 after the beginning of DSS application. Cytokine profiles in colonic tissue were analyzed on the protein level by ELISA and on the mRNA level by real time RT-PCR. Administration of DSS led to an increase in IL-18, IL-12, TNF-alpha, and IFN-gamma protein as well as IP-10 and TNF-alpha mRNA. The increase in IL-18 and IFN-gamma was reduced by ICE inhibition. Pralnacasan prevented DSS-induced colitis in C57BL/6 mice. In C57BL/6 mice, the DSS-induced increase in IP-10 mRNA, but not TNF-alpha mRNA, was completely prevented by ICE inhibition. In conclusion, prevention of colitis in C57BL/6 mice was associated with a suppresion of IP-10 mRNA, but not TNF-alpha mRNA expression, indicating that IL-18-mediated cytokine production is a key element in the pathogenesis of DSS-induced colitis.     

Protective Effect of Lactulose on Dextran Sulfate Sodium-Induced Colonic Inflammation in Rats

Promising results have recently been obtained with pre- and probiotic therapy in ulcerative colitis (UC). The prebiotic potential of lactulose is well established, but it has not yet been investigated in experimental colitis models. The purpose of the study was to examine the effect of lactulose on an UC model induced by 3% dextran sulfate sodium (DSS) solution added to drinking water for 7 days in male Wistar rats. Lactulose (300-1000 mg/kg) or 5-aminosalicylic acid (5-ASA; 150 mg/kg) was administered orally twice daily for 6 days. Colonic ulceration area, colon length, body weight changes, diarrhea/bloody feces, colonic mucosal myeloperoxidase activity (MPO), thiobarbituric acid reactive substances (TBARS), and histology were examined. Treatment of animals with DSS for 7 days resulted in severe colonic lesions accompanied by diarrhea, bloody feces, a decrese in body weight, shortening of the colon length, and an increase in MPO activity as well as TBARS, compared to normal rats. Lactulose treatment ameliorated DSS-induced colitis in a dose-dependent manner, and at 1000 mg/kg all of the parameters examined, except TBARS, were shown to improve significantly as compared to controls. Daily administration of 5-ASA also significantly reduced the severity of colonic lesions following DSS treatment. These results demonstrated the protective effect of lactulose in this rat colitis model and suggested that the background of this lactulose effect may be due to alterations of colonic microflora.     

Local immunity in ulcerative colitis: evidence for defective secretory IgA production.

To investigate local humoral immunity in ulcerative colitis (UC), immunoglobulin (Ig) contents and net Ig production in vitro was assessed using organ cultures of colonic biopsies from 21 patients with quiescent disease and 11 controls. Ig was estimated by enzyme linked immunoassay (ELISA) for IgA, secretory IgA (sIgA), IgM, and IgG. In parallel, numbers of IgA plasma cells were estimated by indirect immunoperoxidase staining of tissue sections for IgA. IgA was the dominant Ig isotype found pre-existing in colonic mucosae, and secreted in vitro. In UC patients, preformed tissue IgA and IgA produced in vitro were significantly increased compared with controls. There was no concomitant increase in amounts of sIgA synthesised in culture, however, although numbers of IgA plasma cells were increased in UC patients by an amount comparable with the increased in vitro IgA production. These results directly show a dysfunction of transepithelial IgA secretion in quiescent ulcerative colitis. Despite a significantly raised concentration of tissue IgG in UC patients, little was produced in vitro in patient and control groups alike, suggesting that mucosal IgG was serum derived, and not linked to local IgA production.     

Systemic Iron Supplementation Replenishes Iron Stores Without Enhancing Colon Carcinogenesis in Murine Models of Ulcerative Colitis: Comparison with Iron-Enriched Diet

Ulcerative colitis (UC) patients frequently require iron supplementation to remedy anemia. The impact of systemic iron supplementation (intraperitoneal injection) on UC-associated carcinogenesis was assessed in mice subjected to cyclic dextran sulfate sodium (DSS) treatment and compared with dietary iron enrichment. Systemic iron supplementation, but not a twofold iron diet, remedied iron deficiency as indicated by the histochemical detection of splenic iron stores. A twofold iron diet, but not systemic iron, increased iron accumulation in colonic luminal contents, at the colonic mucosal surface, and in superficial epithelial cells. Colitis-associated colorectal tumor incidence after 15 DSS cycles was not affected by systemic iron (2/28; 7.1%) compared to nonsupplemented controls (4/28; 14.1%) but was significantly increased by the twofold iron diet (24/33; 72.7%) (P < 0.001). Mechanistic study revealed that systemic iron had no effect on DSS-induced inflammation, or colonic iNOS and COX-2 protein levels, compared to controls. Systemic iron supplementation for 16 weeks replenished splenic iron in a spontaneous colitis model (interleukin-2-deficient mice) and significantly reduced colonic inflammation compared to interleukin-2 (–/–) controls without increasing hyperplastic lesions. These results suggest that iron supplemented systemically could be used to remedy anemia in UC patients without exacerbating inflammation or enhancing colon cancer risk. These findings need to be verified in clinical studies.This work was supported by Research Project Grant RPG-00-034-01-CNE from the American Cancer Society and NIH Grant RO1CA104741-01A1 (G.-Y.Y.).     

Emergence of antigenic glycoprotein structures in ulcerative colitis detected through monoclonal antibodies

The emergence of new glycoprotein structures in colonic mucosa from patients with ulcerative colitis (UC) was assessed through the development of monoclonal antibodies (MAbs). Hybridomas were prepared from mice immunized with mucin glycoproteins purified from UC colonic tissue. Supernatants of 11 fusion products among 1200 fusion products that were screened in a solid-phase binding assay differentially bound UC-derived colonic mucin glycoproteins relative to comparable preparations from normal or Crohn's colitis tissue. These hybridomas were double-cloned to yield MAbs designated as MAbs UC 1-11. Disease-related specificity of MAbs UC 1-11 was determined through assessment of binding to beads coated with mucin glycoproteins purified from individual samples of UC tissue (n = 15), normal tissue (n = 21), and Crohn's colitis tissue (n = 10). Monoclonal antibody UC 7, an MAb of immunoglobulin G2A subclass, showed differential binding in solid-phase assays to UC mucin glycoproteins, with a mean binding of 10,170 +/- 2740 cm per UC glycoprotein-coated bead versus 2300 +/- 1080 and 2470 +/- 1525 cpm for normal and Crohn's colitis-derived glycoproteins, respectively. Monoclonal antibody UC 11 showed similar differential binding to UC mucin glycoproteins (9860 +/- 680 cpm vs. 1770 +/- 420 cpm). Binding specificity in solid-phase assay was mirrored by colonic mucosal staining patterns assessed by indirect immunofluorescent staining. Monoclonal antibody UC 7 specifically stained colonic mucosa from 8 of 10 patients with active UC, none of the samples from 8 normal controls, and none of the samples from 11 disease controls (six with Crohn's colitis, five with other inflammatory disorders). Specific staining was present on both the epithelial surface and on cells scattered within the lamina propria. Staining by MAb UC 7 was also observed in 3 of 4 samples of proximal uninvolved mucosa from patients with left-sided ulcerative colitis and in 3 of 5 samples from UC patients without acute disease activity.     

Rebamipide Attenuates Indomethacin-Induced Gastric Mucosal Lesion Formation by Inhibiting Activation of Leukocytes in Rats

Granulocyte elastase released from activatedleukocytes plays an important role in leukocyteinfiltration. Since activated leukocytes have been shownto be involved in the pathogenesis of gastric mucosal lesion formation induced by nonsteroidalantiinflammatory drugs, inhibition of granulocyteelastase release from activated leukocytes may be usefulin the prevention of these lesions. Rebamipide, a novel antiulcer agent, inhibited granulocyte elastaserelease from activated neutrophils in vitro. Rebamipideand ONO-5046, a granulocyte elastase inhibitor, markedlyinhibited gastric mucosal lesion formation in rats. Gastric myeloperoxidase activity wassignificantly increased 3 hr after indomethacinadministration. This increase was significantlyinhibited by rebamipide and ONO-5046. Cimetidine did notinhibit granulocyte elastase release from activatedneutrophils. Although cimetidine markedly prevented theindomethacin-induced gastric mucosal lesion formation,it did not reduce the gastric myeloperoxidase activity. Therefore, unlike cimetidine, rebamipide mayprevent indomethacin-induced gastric mucosal lesionformation by inhibiting neutrophil activation.     

Human thioredoxin-1 ameliorates experimental murine colitis in association with suppressed macrophage inhibitory factor production

BACKGROUND & AIMS: Thioredoxin-1 (TRX) is a small multifunctional protein with antioxidative and redox-regulating functions. In this study, we investigated the significance of TRX in patients with inflammatory bowel disease (IBD) and the ability and mechanism to ameliorate experimental colitis. METHODS: Serum TRX and macrophage migration inhibitory factor (MIF) levels were measured in patients with IBD. The effects of TRX were evaluated in a dextran sulfate sodium (DSS)-induced colitis model by comparing TRX-overexpressing transgenic (TRX-TG) and control mice. We further evaluated the effect of recombinant human TRX (rhTRX) administration on DSS-induced colitis and colonic inflammation of interleukin (IL)-10 knockout (IL-10 KO) mice. Colonic inflammation was examined clinically and histologically. Proinflammatory cytokine levels were examined in colonic tissues, and MIF levels were measured in colonic tissues and sera in mice. The effect of TRX on MIF production was also analyzed in vitro. RESULTS: Serum TRX and MIF levels were significantly higher in patients with IBD than normal controls, and TRX levels correlated with disease activity. TRX significantly ameliorated DSS-induced colitis and colonic inflammation of IL-10 KO mice. Increase of tumor necrosis factor-alpha and interferon-gamma in colonic tissues was significantly suppressed in TRX-TG mice compared with wild-type mice. MIF levels in colonic tissues and sera were significantly lower in TRX-TG mice than in wild-type mice, irrespective of DSS administration. Anti-TRX treatment exacerbated DSS-induced colitis. In vitro studies demonstrated that rhTRX suppressed MIF production in human monocyte cells. CONCLUSIONS: TRX might have a potential as a novel therapeutic agent for the treatment of IBD.     

Significance of glucocorticoid receptor expression in colonic mucosal cells of patients with ulcerative colitis

AIM: Glucocorticoid (GC) resistant ulcerative colitis (UC) remains a serious disease and is difficult to manage. Although the molecular basis of GC insensitivity is still unknown, GC receptors (GRAAA and GRp) may play an important role in it. This study was aimed to investigate the relationship between the expression of GRa and GRp in colonic mucosal cells of patients with UC, the efficacy of GC therapy and the intensity of inflammation. METHODS: Twenty-five cases of UC were classified into: GC sensitive (n = 16) and GC resistant (n - 9) cases. Patients consisted of mild (n = 6), moderate (n = 8) and severe (n = 11) cases. GRa and GRp expression in colonic mucosal specimens were investigated by immunohistochemistry, and compared between GC resistant and sensitive groups, and also among various degrees of inflammation. RESULTS: All cases were positive for GRa and GRp expression. Both positive association between GRa expression and the response of UC to GC and strong negative association between GRp expression and the response of UC to GC were identified. There was no significant association between GRa/GRp expression and the degree of inflammation of UC. CONCLUSION: These findings suggest that both GRa and GRp may play an important role in the action of GC, and that GRp functions as a dominant negative inhibitor of GRa. Expression of GRa and GRp in colonic mucosal cells of patients with UC may serve as predictors of glucocorticoid response, but can not function as markers of inflammatory intensity.     

Increased Activity and Expression of Gelatinases in Ischemic Colitis

Ischemic colitis results from insufficient blood supply but its pathogenesis is poorly understood. The aim of this study was to determine whether the activity and expression of gelatinases (MMP-9 and MMP-2) are increased in the colonic mucosa of patients with ischemic colitis. MMP-9 and MMP-2 activity and expression were assessed in colonic mucosal specimens from 8 patients with acute ischemic colitis and in 12 controls with a normal colonoscopy. The activity and expression of MMP-9 and MMP-2 were quantified in tissue samples by zymography and western blot, respectively. Colonoscopy was repeated 12 weeks after discharge in two patients and MMP activity was assessed in the slight residual mucosal changes of ischemic colitis. In patients with ischemic colitis, a significant increase in total MMP-9 and MMP-2 activity and expression was found in ulcerated areas compared with noninvolved sites of mucosa. Following resolution of ischemic ulcers the proteolytic activity returned to baseline levels. In addition, the colonic mucosa of controls showed MMP-2 activity, whereas the MMP-9 activity was negligible or not detected. We conclude that ischemic colitis induces increased activity and expression of MMP-9 and MMP-2 in the involved colonic mucosa. These changes may contribute to tissue degradation and remodeling of the colonic mucosa in ischemic colitis.     

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.     

葡聚糖硫酸钠结肠炎模型影响因素的研究进展

自1985年首次报道采用葡聚糖硫酸钠(dextran sulphate sodium,DSS)制备出仓鼠溃疡性结肠炎模型以来,已有大量研究证明DSS结肠炎模型与人类溃疡性结肠炎相似.该模型的病因、临床症状、病理改变及治疗应答均与人类UC相类似;对于研究UC病因、发病机制及UC相关增生和肿瘤,确定治疗手段有重要意义.虽然DSS模型制作简单;但该过程受到多个因素的影响:DSS浓度、给药时间、DSS相对分子质量和动物种属等.如不能正确处理这些因素,很难制造出成功的DSS结肠炎模型.本文主要针对DSS造模影响因素及尚需我们进一步研究和探讨的问题作综述如下.     

Therapeutic effects of four strains of probiotics on experimental colitis in mice

AIM： To investigate the therapeutic effects of four strains of probiotics （E. feacalis, L. acidophilus, C. butyricum and B. adolescentis） on dextran sulphate sodium （DSS）-induced experimental colitis in Balb/c mice. METHODS： Eighty Balb/c mice were randomly divided into 8 groups. Weight-loss, fecal character, fecal occult blood and hematochezia were recorded daily. Disease activity index （DAI） scores were also evaluated everyday. Length of colon was measured and histological scores were evaluated on the 13th day. Myeloperoxidase （MPO） activity was detected. Interleukin-1 （IL-1） and IL-4 expression was detected by ELISA and RT-PCR. RESULTS： The four strains of probiotics relieved the inflammatory condition of DSS-induced experimental colitis in mice. Weight loss was slowed down in all probiotics-treated mice. Even weight gain was observed by the end of probiotics treatment. The DAI and histological scores of probiotics-treated mice were lower than those of mice in the control group （1.9 ± 0.2 vs 8.6 ± 0.4, P 〈 0.05 for E. faecalis）. The length of colon of probiotics-treated mice was longer than that of mice in the control group （10.3 ± 0.34 vs 8.65 ± 0.77, P 〈 0.05 for E. faecalis）. The four strains of probiotics decreased the MP activity and the IL-1 expression, but increased the IL-4 expression. E. faecalis had a better effect on DSS-induced experimental colitis in mice than the other three strains. CONCLUSION： The four strains of probiotics have beneficial effects on experimental colitis in mice, E. faecalis has a better effect on DSS-induced experimental colitis in mice than the other three strains. Supplement of probiotics provides a new therapy for UC.     

Premorbid Steatohepatitis Increases the Seriousness of Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice

Background and AimsThe concurrence of nonalcoholic steatohepatitis (NASH) and ulcerative colitis (UC) is increasingly seen in clinical practice, but the underlying mechanisms remain unclear. This study aimed to develop a mouse model of the phenomenon by combining high-fat high-cholesterol diet (HFHCD)-induced NASH and dextran sulfate sodium (DSS)-induced UC, that would support mechanistic studies.MethodsMale C57BL/6 mice were randomly assigned to two groups receiving either a chow diet or HFHCD for 12 weeks of NASH modeling. The mice were the divided into four subgroups for UC modeling: (1) A control group given a chow diet with normal drinking water; (2) A colitis group given chow diet with 2% DSS in drinking water; (3) A steatohepatitis group given HFHCD with normal drinking water; and (4) A steatohepatitis + colitis group given HFHCD with 2% DSS in drinking water.ResultsNASH plus UC had high mortality (58.3%). Neither NASH nor UC alone were fatal. Although DSS-induced colitis did not exacerbate histological liver injury in HFHCD-fed mice, premorbid NASH significantly increased UC-related gut injury compared with UC alone. It was characterized by a significantly shorter colon, more colonic congestion, and a higher histopathological score (p<0.05). Inflammatory (tumor necrosis factor-alpha, interleukin 1 beta, C-C motif chemokine ligand 2, and nuclear factor kappa B) and apoptotic (Bcl2, Bad, Bim, and Bax) signaling pathways were significantly altered in distal colon tissues collected from mice with steatohepatitis + colitis compared with the other experimental groups.ConclusionsPremorbid steatohepatitis significantly aggravated DSS-induced colitis and brought about a lethal phenotype. Potential links between NASH and UC pathogeneses can be investigated using this model.     

Effects of α-linolenic acid on colonic secretion in rats with experimental colitis

Background Few studies have specifically examined the effects of n-3 polyunsaturated fatty acids (PUFAs) on intestinal water and ion secretion in ulcerative colitis (UC). The aim of this study was to examine the contribution of prostaglandins (PGs) and leukotrienes (LTs) to mucosal secretion in intestines with UC and to evaluate the effect of dietary n-3 PUFAs on diarrhea in UC. Methods We measured the short-circuit current (Isc), using the Ussing chamber method, and fatty acid composition in the colonic mucosa of rats with dextran sulfate sodium (DSS)-induced experimental colitis. The DSS-treated rats were fed either a perilla oil-enriched diet (perilla group) or a soybean oil-enriched diet (soybean group); a control group did not undergo DSS administration. Results The bradykinin-stimulated ΔIsc in the soybean and perilla groups was significantly higher than that in the control group. The mucosal level of arachidonic acid in the perilla group was significantly lower than that in the soybean group. The mucosal levels of α-linolenic acid and EPA in the perilla group were significantly higher than those in the soybean group. The bradykinin-stimulated ΔIsc was significantly suppressed after pretreatment with indomethacin in both the soybean and perilla groups, and was also significantly reduced in both groups after pretreatment with AA861. The suppression of bradykinin-stimulated ΔIsc by the addition of AA861 was significantly higher in the perilla group than in the soybean group. Conclusions Our results suggest that supplementation with α-linolenic acid, in combination with a lipoxygenase inhibitor, could suppress the increase in Cl- secretion in patients with UC.     

Novel Antioxidants Zolimid and AEOL11201 Ameliorate Colitis in Rats

The mechanism of tissue damage in ulcerative colitis (UC) is unknown. However, recent evidence suggests that reactive oxygen species (ROS) are critical mediators of inflammation, and tissue damage in UC and antioxidants could be beneficial in the treatment of UC. Our aim was to evaluate the effects of two new antioxidants, Zolimid and AEOL11201 on experimental colitis. Antioxidants or vehicle were given to rats for five days after induction of colitis by intrarectal administration of 4% acetic acid. Severity of colitis was assessed on day 5. Zolimid and AEOL11201 significantly improved acetic acid-induced colitis. Both Zolimid and AEOL11201 significantly decreased the severity of diarrhea, and severity of macroscopic and histological changes in the colon. Both agents also significantly decreased colonic MPO levels. In conclusion, Zolimid and AEOL11201 are effective antiinflammatory agents in an animal model of colitis. Further studies are needed to evaluate their beneficial therapeutic effects in patients with UC.