急性结肠炎慢性化小鼠模型的建立

背景：改变葡聚糖硫酸钠（DSS）的浓度和作用时间可建立适当的结肠炎模型，对于进一步研究其病因和发病机制具有重要意义。目的：建立急性结肠炎慢性化的小鼠模型，并探讨其病理学特征。方法：48只C57BL／6小鼠分为模型组和正常对照组。模型组自由饮用3％DSS溶液，5d后改饮用蒸馏水3周，建立急性结肠炎慢性化模型。正常对照组饮用蒸馏水26d。每日行疾病活动指数（DAI）评分。于实验第5、12、19、26d分别处死两组各6只小鼠，行结肠大体形态观察、组织病理学评分和炎症评分。结果：造模第5d，模型组小鼠均出现腹泻、血便、体质量减轻等症状，光学显微镜下可见结肠多灶性浅溃疡，上皮缺失或少许残留，隐窝破坏，杯状细胞减少，以中性粒细胞为主的炎性细胞浸润黏膜和黏膜下层。改饮用蒸馏水3周后，小鼠体质量恢复，腹泻减轻，血便等症状消失，但仍见灶性小溃疡，伴上皮不规则再生和数量较多的炎性细胞浸润。急、慢性期肠道病变均以远段结肠为重。结论：单个循环饮用3％DSS可诱导C57BI怕小鼠发生与人类临床和病理表现相似的急、慢性结肠炎，为进一步研究结肠炎提供了新的模型系统。     

Syndecan-1在小鼠结肠炎模型中的表达和意义

背景：Syndecan-1是一种由硫酸乙酰肝素链和硫酸软骨素链修饰的Ⅰ型跨膜蛋白,主要表达于上皮细胞和内皮细胞,与炎症发生的各个环节均有密切联系。目的：观察结肠炎模型小鼠结肠组织中Syndecan-1的表达,探讨其在炎症性肠病（IBD）中的作用。方法：以三硝基苯磺酸（TNBS）-乙醇溶液灌肠诱导小鼠结肠炎模型。于造模后3、7、14、21d分批处死各组小鼠,于光学显微镜下观察结肠组织学改变并评分;分别以逆转录聚合酶链反应（RT-PCR）和免疫组化方法检测结肠组织Syndecan-1mRNA和蛋白水平的表达。结果：各模型组结肠组织学评分均显著高于正常对照组（P〈0.01）,以造模后第3d最高,其后逐渐减低。各模型组结肠组织Syndecan-1mRNA表达水平与正常对照组相比差异无统计学意义,但蛋白表达评分均显著低于正常对照组（P〈0.01）,以造模后第3d最低,其后逐渐回升。结论：结肠组织Syndecan-1蛋白表达与模型小鼠结肠炎病变严重程度有关,有可能成为IBD诊治和病情监测的指标之一。     

T辅助细胞在右旋葡聚糖硫酸钠诱导的小鼠结肠炎中的作用研究

目的　探讨Th1/Th2细胞在右旋葡聚糖硫酸钠 (DSS)诱导小鼠结肠炎中的作用。方法　利用细胞内细胞因子流式细胞检测法 ,测定DSS诱导急、慢性结肠炎小鼠肠黏膜和脾脏单核细胞 (SMC)中Th1/Th2比例。结果　①结肠炎急性期 ,小鼠肠黏膜固有层单核细胞 (LPMC)中Th1细胞为 (8.90± 1.2 3) % ,较对照组升高 (P <0 .0 5 ) ;Th2细胞占 (3.2 5± 1.2 5 ) % ,与对照组差异无显著性 (P >0 .0 5 ) ;Th1/Th2比例为 3.0 9± 1.18,较对照组升高 (P <0 .0 5 )。②在慢性期 ,肠黏膜LPMC中Th1、Th2细胞分别占 (5 .5 2± 1.2 8) %和 (10 .0 8± 1.75 ) % ,均较对照组升高 (P <0 .0 5 ) ;Th1/Th2比例为 0 .5 2± 0 .2 1,较对照组降低 (P <0 .0 5 )。脾脏SMC中Th1、Th2百分比、Th1/Th2比例 ,各期无明显差异。结论　DSS结肠炎是一种以肠黏膜免疫功能紊乱为主的炎症性病变。Th1优势反应可能与急性期损伤有关 ,而Th2优势反应可能在炎症的慢性化过程中发挥重要作用。     

葡聚糖硫酸钠自由饮用与定量灌胃诱导小鼠急性结肠炎模型的比较研究

背景：自由饮用葡聚糖硫酸钠（DSS）诱导的鼠类急性结肠炎模型均一性欠佳,动物死亡率较高。目的：评估2%DSS自由饮用或定量灌胃诱导的小鼠急性结肠炎模型模拟人类溃疡性结肠炎（UC）的效果和均一性。方法：予ICR小鼠2%DSS自由饮用或定量灌胃建立急性结肠炎模型,检测并比较正常对照组和两组模型小鼠的症状出现时间和频率、疾病活动指数（DAI）、DSS消耗量、死亡率、结肠长度、结肠损伤大体评分（MACD）、结肠组织病理学表现以及外周血白细胞计数和分类。结果：两组模型小鼠均出现类似人类UC的症状和组织病理学改变,结肠显著短缩,DAI、MACD以及外周血白细胞计数和中性粒细胞百分比显著高于正常对照组。与DSS自由饮用组相比,DSS定量灌胃组小鼠症状出现时间更为一致,症状出现率显著增高,动物死亡率和DSS消耗量显著减低。结论：2%DSS定量灌胃诱导的小鼠急性结肠炎模型能较稳定地模拟人类UC,均一性高,动物死亡率低。     

葡聚糖硫酸钠诱导小鼠实验性结肠炎的临床和组织病理学特征研究

目的研究葡聚糖硫酸钠(DSS)诱导小鼠实验性结肠炎的临床和病理特征,以便于指导选择合适的溃疡性结肠炎(ulcerative colitis,UC)小鼠模型。方法予3%DSS溶液喂饲野生型C57BL/6成年小鼠诱导急性结肠炎模型,分别于第0天、第3天、第5天、第7天和第10天麻醉处死小鼠,取结肠观察不同时期结肠病理学特征,造模过程中连续观察并记录小鼠体质量、大便和死亡情况。结果小鼠造模第3天开始出现粪便潜血,第5天开始出现血便,第10天开始出现死亡小鼠,死亡率为30%。DSS诱导小鼠急性结肠炎模型疾病活动指数第3天后与饮用纯净水的小鼠比较明显增高(P0.05)。小鼠结肠炎造模第3天黏膜上皮细胞开始逐渐丧失,第7~10天最为严重;隐窝结构的紊乱从第3天开始发生,第7天出现固有层塌陷;炎性细胞浸润从第3天开始数量逐渐增加,第10天最为严重。DSS诱导小鼠急性结肠炎模型结肠组织病理评分第5天后与饮用纯净水的小鼠比较明显增高(P0.05)。结论 3%DSS诱导野生型C57BL/6成年小鼠急性结肠炎模型可用于UC的实验研究,第3天出现明显的炎症表现,第7天模型较理想,小鼠死亡少。     

益生菌对溃疡性结肠炎模型大鼠肠黏膜Toll样受体表达的影响及其意义

目的探讨益生菌对葡聚糖硫酸钠诱导的溃疡性结肠炎模型大鼠肠黏膜Toll样受体(TLR)的影响及其临床意义。方法 40只SD大鼠随机分为正常对照组、模型组、益生菌组和美沙拉嗪组。对照组正常饲养,不予任何处理;模型组、益生菌组和美沙拉嗪组给予含5%葡聚糖硫酸钠饮用水10 d建立溃疡性结肠炎模型,益生菌组和美沙拉嗪组于第11天分别给予酪酸梭菌活菌和美沙拉嗪灌胃治疗14 d。14 d后处死所有大鼠,观察疾病活动指数,进行组织学评分,RT-PCR法检测TLR2和TLR4的表达,免疫组化方法检测转转录因子(NF)-κB的活性。结果模型组的疾病活动指数和组织学评分显著高于对照组,益生菌组和美沙拉嗪组低于模型组(P<0.05)。模型组TLR2和TLR4的表达显著高于对照组,益生菌组和美沙拉嗪组高于对照组且低于模型组(P<0.05),而益生菌组和美沙拉嗪组间差异不显著(P>0.05)。模型组NF-κB的活性显著高于对照组,益生菌组和美沙拉嗪组高于对照组且低于模型组(P<0.05),而益生菌组和美沙拉嗪组间差异不显著(P>0.05)。结论溃疡性结肠炎模型大鼠中TLR表达异常,NF-κB的活性增加,益生菌及美沙拉嗪制剂可降低溃疡性结肠炎模型大鼠TLR表达和NF-κB的活性,是治疗溃疡性结肠炎的有效方法。     

丹参对右旋葡聚糖硫酸钠诱导小鼠结肠炎的疗效观察

目的 :评价丹参预防及治疗右旋葡聚糖硫酸钠 (DSS)结肠炎小鼠的有效性。方法 :2 0只正常小鼠随机分为两组 ,饮用 DSS7d,同时预防组用丹参 ,对照组用 0 .85 %氯化钠溶液。另 2 0只 DSS诱导的结肠炎小鼠随机分为两组 ,治疗组用丹参 ,对照组用 0 .85 %氯化钠溶液 7d。用疾病活动指数 (DAI)、组织学评分和马休斯猩红蓝(MSB)纤维素染色检测微血栓以评价疗效。结果 :丹参在预防组部分降低微血栓的形成 ,对照组 10例有 6例微血栓阳性 ,预防组 3例阳性。丹参治疗组与对照组的 DAI、直肠、横结肠组织学评分分别为 0 .4 5、0 .4 8(P>0 .0 5 ) ,1.36、1.76 (P<0 .0 5 ) ,1.35、1.6 0 (P<0 .0 5 )。结论 :丹参可能部分抑制微血栓形成和减轻 DSS结肠炎小鼠结肠炎症 ,提示丹参用于溃疡性结肠炎治疗也可能有效。     

小鼠实验性结肠炎中骨桥蛋白的变化

目的 观察骨桥蛋白(osteopontin,OPN)在右旋葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导的小鼠结肠炎中的变化,探讨OPN在炎症性肠病(inflammatory bowel disease,IBD)发病中的作用.方法 32只雄性BALB/C小鼠随机分为对照组(予蒸馏水饮用23 d)、模型组(5%DSS饮用9 d后2.5%DSS维持2周)、柳氮磺胺吡啶(SASP)治疗组(在模型组基础上从第10天起予SASP 600 mg/kg灌胃2周)和英夫利昔治疗组(在模型组基础上在第10天予尾静脉注射英夫利昔100 mg/kg 1次).酶联免疫法检测小鼠血浆OPN浓度,逆转录聚合酶链反应和Western印迹法检测小鼠结肠组织中OPN的mRNA水平和蛋白质水平表达,免疫组化法检测OPN在结肠组织中的定位表达.结果 各组小鼠的血浆OPN浓度分别为(5.26±1.93)、(10.21±2.37)、(4.58±1.83)和(4.82±1.83)ng/ml;结肠组织中OPN mRNA表达量分别为(0.36±0.16)、(0.71±0.17)、(0.32±0.07)和(0.42±0.22);结肠组织中OPN的蛋白表达量分别为(0.44±0.10)、(0.85±0.04)、(0.61±0.11)和(0.58±0.17);结肠黏膜固有层OPN阳性细胞数分别为(46.6±10.9)、(155.5±43.8)、(73.1±6.8)和(70.6±8.3).与对照组相比,模型组血浆和结肠组织中OPN的表达明显增高(P均<0.05),SASP治疗组和英夫利昔治疗组OPN的表达均较SASP治疗组下降(P均<0.05),SASP治疗组和英夫利昔治疗组OPN的表达差异无统计学意义.结论 OPN在DSS诱导的小鼠结肠炎中表达增加,经药物治疗后表达降低.OPN促进了DSS诱导的小鼠结肠炎的发生.     

小鼠葡聚糖硫酸钠急性溃疡性结肠炎模型的建立和评价

目的探索葡聚糖硫酸钠(dextransulfatesodium,DSS)诱导UC急性模型的浓度及时间。方法用C57BL/6小鼠自由饮用DSS溶液(3%、5%、8%)的方法建立急性UC模型,正常组饮用蒸馏水作为对照。通过疾病活动指数(DAI)和肠黏膜组织损伤指数(HI)来评价结肠的形态和组织病理学改变。结果DAI评分随着浓度(0、3%、5%和8%)的增加呈线性增加(1.50±0.53、7.71±1.38、9.14±1.03和9.71±0.61),呈浓度依赖性(组间比较P<0.05);远端结肠HI评分(0、5.93±1.65、7.00±1.07、7.75±0.46)和近端结肠HI评分(0、4.25±1.58、5.13±3.17、6.50±1.41)无浓度依赖性(仅3%组vs8%组P<0.05);死亡率随浓度的增加而升高(0、7.10%、28.60%和57.10%)。结论DSS模型的临床表现和病理表现与人类UC及其相似,是理想的UC模型。DSS模型结肠炎症程度的轻重与浓度无明显相关。采用C57BL/6小鼠饮用3%DSS(分子量为40000左右)溶液5天的方法可建立理想的UC急性模型。     

肝素治疗右旋葡聚糖硫酸钠诱导小鼠结肠炎的疗效观察

目的　评价肝素预防及治疗右旋葡聚糖硫酸钠 (DSS)诱导小鼠结肠炎的有效性。方法　32只小鼠中 ,16只正常小鼠分成两组 ,饮用DSS 7d的同时预防组皮下注射肝素 ,对照组皮下注射生理盐水 ;另 16只饮用DSS 7d后诱导结肠炎的小鼠分成两组 ,治疗组皮下注射肝素 ,对照组皮下注射生理盐水。用疾病活动指数、组织学评分、TNF α的表达和马休斯猩红兰 (MSB)检测微血栓评价疗效。结果　肝素在预防组降低微血栓的形成 ,对照组 8只中 4只微血栓阳性 ,预防组均阴性 (P =0 .0 38)。治疗组组织学评分、TNF α的表达明显降低 ,治疗组与对照组的直肠、横结肠组织学评分和TNF α的表达分别为 1.33和 1.85 (P <0 .0 5 ) ,0 .92和 1.6 8(P <0 .0 5 ) ,(5 .5± 3.5 ) %和 (10 .8± 4.2 ) % (P <0 .0 5 )。结论　肝素可抑制DSS诱导结肠炎小鼠血栓形成和结肠炎症 ,实验结果提示肝素用于溃疡性结肠炎治疗也可能有效     

Geranylgeranylacetone protects mice from dextran sulfate sodium-induced colitis

OBJECTIVE: Geranylgeranylacetone (GGA) has recently been reported to induce heat shock protein (HSP) 70, which has a protective function against inflammation. We investigated the therapeutic effects of oral administration of GGA on dextran sulfate sodium (DSS)-induced colitis in mice. MATERIALS AND METHODS: BALB/c mice were given 3% DSS solution orally for 7 days to induce colitis. The disease activity of colitis was assessed clinically every day, and histology in the colon was evaluated at 7 days post-DSS. The levels of myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in the colon tissues were also examined. In addition, expression of HSPs 25, 40, 70 and 90 in the colon tissue was determined by Western blot analysis. Mice were orally administered GGA (50-500 mg/kg) when treatment of DSS started. RESULTS: It was found that GGA significantly reduced the clinical severity of colitis and suppressed the levels of MPO activity, TNF-alpha and IFN-gamma induced by DSS in the colon. On the other hand, GGA enhanced the expression of HSP70 in the colon of mice given DSS. CONCLUSIONS: Taken together, these results suggest that GGA is a new anti-inflammatory drug that could be useful in the treatment of colitis such as inflammatory bowel disease.     

Geranylgeranylacetone protects mice from dextran sulfate sodium-induced colitis

Objective. Geranylgeranylacetone (GGA) has recently been reported to induce heat shock protein (HSP) 70, which has a protective function against inflammation. We investigated the therapeutic effects of oral administration of GGA on dextran sulfate sodium (DSS)-induced colitis in mice.Material and methods. BALB/c mice were given 3% DSS solution orally for 7?days to induce colitis. The disease activity of colitis was assessed clinically every day, and histology in the colon was evaluated at 7?days post-DSS. The levels of myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in the colon tissues were also examined. In addition, expression of HSPs 25, 40, 70 and 90 in the colon tissue was determined by Western blot analysis. Mice were orally administered GGA (50–500?mg/kg) when treatment of DSS started.Results. It was found that GGA significantly reduced the clinical severity of colitis and suppressed the levels of MPO activity, TNF-α and IFN-γ induced by DSS in the colon. On the other hand, GGA enhanced the expression of HSP70 in the colon of mice given DSS. HSP70-positive cells were identified in the epithelial cells of the colon from mice treated with GGA and DSS.Conclusions. Taken together, these results suggest that GGA is a new anti-inflammatory drug that could be useful in the treatment of colitis such as inflammatory bowel disease.     

Involvement of lymphocytes in dextran sulfate sodium-induced experimental colitis

AIM: To investigate the roles of lymphocytes in the development of dextran sulfate sodium-induced colitis. METHODS: Using various doses of dextran sulfate sodium (DSS), we induced colitis in wild-type B6 control and Rag-1 knockout (H-2b haplotype) mice, and evaluated the colitis in terms of symptomatic and histologic parameters, such as weight loss, survival, severity of diarrhea, shortage of colon length and histological changes. Symptomatic parameters were checked daily and histological changes were scored. RESULTS: Although development of colitis in Rag-1 knockout mice treated with high dose (5%) of DSS was comparable to that in B6 control mice, colitis progression was much more tolerable in Rag-1 knockout mice compared to than in B6 mice treated with low dose (1.5%) DSS. Symptomatic parameters as well as histopathologic changes were improved in Rag-1 knockout mice. CONCLUSION: These results indicate that the presence of lymphocytes contributes to colitis progression at low dose of DSS stimulation. Lymphocytes may play roles as an aggravating factor in DSS-induced colitis.     

Compensatory response of colon tissue to dextran sulfate sodium-induced colitis

Depletion of goblet cells (the main mucin-producing cells in the colon) is one of the most reliable histological characteristics of ulcerative colitis, whereas a major symptom of this disease is bloody diarrhea containing a large amount of mucus. The discrepancy between these phenomena was investigated in a time-course study in rats with experimental colitis induced by treatment with oral dextran sulfate sodium (DSS) for 1, 3, or 5 days. Biochemical analysis showed a reduction in mucin content in the distal side of the colon that was proportional to the duration of DSS administration. In the proximal side of the colon, however, there was a significant increase in mucin content already on the first day of treatment with DSS. This increase in colonic mucin content continued for the 5 days of treatment. In the distal side, both sulfomucin and sialomucin decreased proportionally to the duration of DSS administration. In the proximal side, there was an increase in high iron diamine-Alcian blue-positive mucins, and confirming the proliferation of goblet cells. The proliferated glands were predominantly sialylated. Goblet cell depletion and an increase in mucin production occurred in different parts of the colon. This phenomenon may be a type of compensatory function of colon tissue in response to the localized decrease of mucin production in certain portions of the colon. (Received Sept. 7, 1998; accepted Nov. 27, 1998)     

Conditioned secretome of adipose-derived stem cells improves dextran sulfate sodium-induced colitis in mice

BACKGROUNDInflammatory bowel diseases (IBD) is related to uncontrolled immune response. Currently, there is no successful treatment for significant improvement in IBD. Stem cells display their therapeutic effects through their repopulating capacity or secreting factors. AIMTo investigate the effects of conditioned mouse adipose-derived stem cells (mADSCs) secretome on colitis-induced mice. METHODSmADSCs were isolated from adipose tissue of C57BL/6 mice. Conditioned mADSCs secrectome was obtained by culturing of mADSCs with lipopolysaccharides (LPS, 1 μg/mL) for 24 h. Acute colitis was induced by 2% dextran sulfate sodium (DSS) drinking water for 7 d and then normal drinking water for 4 d. The mice were treated with normal culture medium (NM group), conditioned mADSCs secretome (CM group) or mADSCs (SC group). The length of colon and histopatholgy of colon tissues were evaluated. The mRNA expression levels of inflammatory cytokines in colon tissue and the serum interleukin (IL)-6 levels were determined. RESULTSThe isolated mADSCs maintained the mADSCs specific gene expression profiles during experiment. The conditioned mADSCs secretome released by the treatment of mADSCs with LPS contained mainly inflammatory chemokines, colony-stimulating factors and inflammatory cytokines. The loss of body weight and reduction in colon length were ameliorated in the CM group. The conditioned mADSCs secretome reduced the histological score in colon tissue. The expression of IL-1b and IL-6 mRNAs in colon tissues significantly inhibited in the CM group compared to SC group and NM group, respectively. The elevation of serum IL-6 levels was also ameliorated in the CM group. These results indicate that the conditioned mADSCs secretome suppressed the synthesis of inflammatory cytokines in damaged colon tissue and the elevation of serum IL-6 concentration in DSS-induced miceCONCLUSIONConditioned mADSCs secretome might play regenerative roles by the suppression of IL-6 in serum and tissue during acute colitis, and may be more effective than stem cells themselves in the regeneration of colon tissue.     

Kefir treatment ameliorates dextran sulfate sodium-induced colitis in rats

AIM: To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium(DSS) in rats.METHODS: Twenty-four male Wistar-albino rats were randomized into four groups: normal control,kefircontrol,colitis,and kefir-colitis groups. Rats in the normal and kefir-control groups were administered tap water as drinking water for 14 d. Rats in the colitis and kefir-colitis groups were administered a 3% DSS solution as drinking water for 8-14 d to induce colitis. Rats in the kefir-control and kefir-colitis groups were administered 5 m L kefir once a day for 14 d while rats in the normal control and colitis group were administered an identical volume of the placebo(skim milk) using an orogastric feeding tube. Clinical colitis was evaluated with reference to the disease activity index(DAI),based on daily weight loss,stool consistency,and presence of bleeding in feces. Rats were sacrificed on the 15 th day,blood specimens were collected,and colon tissues were rapidly removed. Levels of myeloperoxidase(MPO),tumor necrosisfactor(TNF)-α,interleukin(IL)-10,malondialdehyde,and inducible nitric oxide synthase(i NOS) were measured in colon tissue.RESULTS: The DAI was lower in the kefir-colitis group than in the colitis group(on the 3rd and 5th days of colitis induction; P 0.01). The DAI was also significantly higher in the colitis group between days 2 and 6 of colitis induction when compared to the normal control and kefir-control groups. The DAI was statistically higher only on the 6th day in the kefircolitis group when compared to that in the normal control groups. Increased colon weight and decreased colon length were observed in colitis-induced rats. Mean colon length in the colitis group was significantly shorter than that of the kefir-control group. Kefir treatment significantly decreased histologic colitis scores(P 0.05). MPO activity in the colitis group was significantly higher than in the kefir-control group(P 0.05). Kefir treatment significantly reduced the DSS colitis-induced TNF-α increase(P 0.01). No statistically significant differences were observed among groups for IL-10 and MDA levels. Colon tissue i NOS levels in the colitis group were significantly higher than those in the control and kefir-colitis groups(P 0.05).CONCLUSION: Kefir reduces the clinical DAI and histologic colitis scores in a DSS-induced colitis model,possibly via reduction of MPO,TNF-α,and i NOS levels.     

Amelioration of dextran sulfate sodium-induced colitis by anti-macrophage migration inhibitory factor antibody in mice

BACKGROUND & AIMS: We investigated the effects of macrophage migration inhibitory factor (MIF) antibodies in experimental colitis-induced dextran sulfate sodium (DSS) and trinitrobenzenesulfonic acid (TNBS) and examined whether plasma levels of MIF were elevated in patients with inflammatory bowel disease (IBD). METHODS: BALB/c or C57BL/6 mice were fed 4% DSS in their drinking water for up to 7 days with and without administration of an anti-MIF antibody every 2 days. The severity of inflammation in the cecum and colon was assessed by clinical signs and histologic scoring. Tissue levels of MIF, tumor necrosis factor (TNF)-alpha, interferon gamma (IFN-gamma), interleukin (IL)-4, and matrix metalloproteinase (MMP)-13 messenger RNA (mRNA) were measured. The effects of anti-MIF antibody on chronic colitis induced by TNBS was assessed in BALB/c mice. Plasma MIF concentrations were assayed in patients with Crohn's disease, ulcerative colitis, and healthy controls. RESULTS: During DSS-induced colitis, colonic MIF mRNA expression was increased. Clinical signs and histopathologic features were significantly improved in animals given anti-MIF antibody. DSS-induced up-regulation of colonic TNF-alpha and IFN-gamma were significantly suppressed in animals given the anti-MIF antibody. Colonic IL-4 was decreased during DSS but restored to baseline by the anti-MIF antibody. The anti-MIF antibody prevented MMP-13 up-regulation by DSS and ameliorated TNBS colitis. Plasma MIF was elevated in patients with Crohn's disease or ulcerative colitis compared with healthy controls. CONCLUSIONS: We conclude that anti-MIF antibodies reduce the severity of experimental colitis and limit the up-regulation of Th1-type cytokines. Anti-MIF antibodies are of potential therapeutic use in IBD.