Improvement Of Inflammatory Bowel Disease Research Articles

Coprococcus eutactus, a Potent Probiotic, Alleviates Colitis via Acetate-Mediated IgA Response and Microbiota Restoration.

Inflammatory bowel disease (IBD) is a complex disease characterized by relapsing episodes of inflammation of the colonic mucosa. Research into IBD suggests that this disease condition is caused by alterations in resident mucosal bacterial populations. Our previous study showed that Coprococcus was significantly elevated during the improvement of IBD. Human metagenome database GMrepo also indicates Coprococcus, in particular, Coprococcus eutactus (C. eutactus), which was negatively associated with IBD. The current study implied the alleviated effects and mechanisms of C. eutactus on dextran sodium sulfate-induced experimental colitis mice. Gavage with C. eutactus-ameliorated acute colitis, as evidenced, relieved weight loss, decreased concentrations of proinflammatory cytokines TNF-α, IL-1β, and IL-6, and increased anti-inflammatory factors, IL-4, IL-5, and IL-10. In addition, C. eutactus enhanced the maturation of goblet cells and the expressions of mucins and restored the expressions of tight junction proteins such as claudin-1, occludin, and ZO-1. As a short-chain fatty acid-producing bacterium, C. eutactus mainly generates acetic acid. Interestingly, not only high levels of secretory immunoglobulin A (SIgA) but also increased IgA-producing plasma cells were observed in colitis mice during the administration of C. eutactus. Importantly, our data demonstrated that colonic SIgA is specifically coated on pathogens of Enterobacteriaceae. Owing to the selective binding effect of SIgA on microorganisms, the microbial diversity in the intestinal lumen and mucosa of C. eutactus-treated colitis mice was significantly restored, and the microbiota structure was remodeled. These findings provide substantial insight that C. eutactus as a promising probiotic can ameliorate colitis. In conclusion, our findings may deliver a novel approach to the prevention and biotherapy of IBD.

Clinical and Endoscopic Improvement of Inflammatory Bowel Disease with Curcumin Therapy: Experiences from Clinical Studies

Inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, is a chronic inflammatory condition of the intestine and one of etiological factor for colon cancer development. Incidences of inflammatory bowel disease is still high around the world, even with current therapy, emerging the need for innovational approach to increase the achievement of disease improvement and remission. Curcumin is a natural compound derived from Curcuma longa and has been well known with its anti-inflammatory properties which is possible to be beneficial for inflammatory bowel disease. This review aims to provide clinical evidences of effectively and safety profile of curcumin in treating inflammatory bowel disease, both Crohn’s disease and ulcerative colitis, and viewing the future prospect of curcumin to be an effective adjuvant therapy to prevent the relapse of inflammatory bowel disease.

Efficacy of oral consumption of curcumin/ for symptom improvement in inflammatory bowel disease: A systematic review of animal models and a meta-analysis of randomized clinical trials

The roots of the vegetal Curcuma due to its high content of polyphenols, has been used successfully in several clinical situations. This review assessed the effect of curcumin/Curcuma longa on symptoms and metabolic changes in inflammatory bowel disease (IBD). A systematic review of animal models and randomized clinical trials (RCTs) was conducted by searching the following electronic databases: PubMed, CENTRAL, LILACS, Science Direct, and ClinicalTrials.gov. From 997 found records, 62 were included. More than 90% of the animal studies reported an improvement in macroscopic, histologic and/or functional activity; 80% identified decreased oxidative and/or inflammatory biomarkers in animals treated with curcumin. Among the RCTs, intention-to-treat analysis showed that oral curcumin was effective in inducing clinical remission (n = 281, RR: 3.15 CI 95% [1.22–8.10] p = 0.0017; i² = 72.2%, p = 0.006) and clinical response (n = 259, RR: 1.60 CI 95% [1.09–2.35] p = 0.0017; i² = 59.7%, p = 0.042) but not endoscopic remission (n = 161, RR: 2.91 CI 95% [0.58–14.58] p = 0.195; i² = 72.7%, p = 0.026). These results confirm that oral supplementation with curcumin/Curcuma longa has beneficial actions in animal colitis and, when associated with drug therapy, is effective in the treatment of patients with IBD.

Berberine improved experimental chronic colitis by regulating interferon-\u03b3- and IL-17A-producing lamina propria CD4+ T cells through AMPK activation

The herbal medicine berberine (BBR) has been recently shown to be an AMP-activated protein kinase (AMPK) productive activator with various properties that induce anti-inflammatory responses. We investigated the effects of BBR on the mechanisms of mucosal CD4+T cell activation in vitro and on the inflammatory responses in T cell transfer mouse models of inflammatory bowel disease (IBD). We examined the favorable effects of BBR in vitro, using lamina propria (LP) CD4+ T cells in T cell transfer IBD models in which SCID mice had been injected with CD4+CD45RBhigh T cells. BBR suppressed the frequency of IFN-γ- and Il-17A-producing LP CD4+ T cells. This effect was found to be regulated by AMPK activation possibly induced by oxidative phosphorylation inhibition. We then examined the effects of BBR on the same IBD models in vivo. BBR-fed mice showed AMPK activation in the LPCD4+ T cells and an improvement of colitis. Our study newly showed that the BBR-induced AMPK activation of mucosal CD4+ T cells resulted in an improvement of IBD and underscored the importance of AMPK activity in colonic inflammation.

Probiotic potentials of cereal-based beverages

ABSTRACTProbiotics offer remarkable potential for the prevention and management of various infective and noninfective disorders. They are reported to play key roles in the suppression of gastrointestinal infections, antimicrobial activity, improvement in lactose metabolism, reduction in serum cholesterol, immune system stimulation, antimutagenic properties, anticarcinogenic properties, anti-diarrheal properties, and improvement in inflammatory bowel disease. Although probiotic foods are classically confined to beverages and cheese, containing live organisms of the lactic acid bacteria family, such health-promoting foods are traditionally dairy-based, comprising milk and its fermented products. However, recent research focuses on the probiotic potentials of fermented cereal-based beverages which are especially consumed in developing countries characterized by low nutritional security and high incidence of gut pathogen infections. Moreover, lactose intolerance and cholesterol content associated with dairy products, coupled with the vegetarian tendencies of diverse populations in the third world, tend to enforce the recent recourse to nondairy beverages. Probiotic microorganisms are mostly of human or animal origin; however, strains recognized as probiotics are also found in nondairy fermented substrates. This review examines the potentials of some traditional cereal-based beverages to serve as probiotic foods, their microbial and functional properties, as well as their process optimization and storage for enhanced utilization.

Bariatric surgery in inflammatory bowel disease; case report and review of the literature

Inflammatory bowel disease (IBD) is rarely associated with obesity, as malabsorption is a common feature of these diseases (1). However, some patients may experience morbid obesity and associated complications refractory to dietary treatment and benefit from bariatric surgery. It has even been postulated that surgery may result in improvement of IBD by reducing inflammatory markers (2). However, patients may experience a higher incidence of complications following surgery in the context of immunosuppressive therapy and prior malabsorption. Therefore, if surgery is performed, careful patient selection and individualization of technique are essential. We present a patient diagnosed with ulcerative colitis who presented severe protein malnutrition after bariatric surgery type bilio-pancreatic diversion and review the available literature.

S1746 Rethinking the Role of IL-13 in Chronic 2,4,6-Trinitrobenzene Sulfonic Acid (TNBS) Colitis Induced Fibrosis

BACKGROUND: Mast cells play a key role in the pathophysiology of inflammatory bowel disease (IBD). Tranilast, N-(3,4-dimethoxycinnamoyl) anthranilic acid, a mast cell stabilizer, has been empirically used for IBD in Japan. The mechanism of tranilast in the improvement of IBD, however, has not yet been clearly delineated, and requires further investigation. Recently, heme oxygenase (HO)-1 has attracted attention in the pro-inflammationmechanism of tranilast. Aim: To investigate the role of tranilast for the treatment of IBD, and elucidated the mechanism and involvement of HO-1 in this effect, we administered tranilast intrarectally to dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: Colitis was induced in C57BL/6(B6) mice by adding 3% DSS in drinking water ad libium for 5 days. Tranilast was administered by enema on day 0, day 2, and day 4 after induction of colitis. The disease activity index (DAI) and degree of colon injury were determined to know the clinical course of colitis. Toluidine blue staining was carried out to identify the mast cell. Staining for HO1 with immunofluorescence to evaluate the expression of HO-1 in the colon. Total RNA was extracted from colon specimens with quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Tranilast ameliorated DSS colitis clinically and pathologically with decreased number and degranulation of mast cells in the colon of DSS colitis. mRNA expression was increased for tumor necrosis factor(TNF)-α, interferon(IFN)-γ, interleukin (IL)-6, and decreased that for IL-10 in the colon of DSS colitis. In contrast, tranilast markedly decreased expression of mRNAs for the proinflammatory cytokines, and increased that of the anti-inflammatory cytokines. Moreover, tranilast increased HO-1 expression on colonic epithelial cells as well as on colon infiltrating cells of DSS colitis. CONCLUSION: Tranilast ameliorated DSS colitis by regulating mast cell degranulation, decreasing inflammatory cytokines and increasing anti-inflammatory cytokines. Tranilast might exert these effects partly through enhanced HO-1 expression in the colon, suggesting a potential adjunctive therapy for IBD.

S1742 Rectal Administration of Tranilast Ameliorated Acute Colitis in Mice Through Increased Expression of Heme Oxygenase-1

BACKGROUND: Mast cells play a key role in the pathophysiology of inflammatory bowel disease (IBD). Tranilast, N-(3,4-dimethoxycinnamoyl) anthranilic acid, a mast cell stabilizer, has been empirically used for IBD in Japan. The mechanism of tranilast in the improvement of IBD, however, has not yet been clearly delineated, and requires further investigation. Recently, heme oxygenase (HO)-1 has attracted attention in the pro-inflammationmechanism of tranilast. Aim: To investigate the role of tranilast for the treatment of IBD, and elucidated the mechanism and involvement of HO-1 in this effect, we administered tranilast intrarectally to dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: Colitis was induced in C57BL/6(B6) mice by adding 3% DSS in drinking water ad libium for 5 days. Tranilast was administered by enema on day 0, day 2, and day 4 after induction of colitis. The disease activity index (DAI) and degree of colon injury were determined to know the clinical course of colitis. Toluidine blue staining was carried out to identify the mast cell. Staining for HO1 with immunofluorescence to evaluate the expression of HO-1 in the colon. Total RNA was extracted from colon specimens with quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Tranilast ameliorated DSS colitis clinically and pathologically with decreased number and degranulation of mast cells in the colon of DSS colitis. mRNA expression was increased for tumor necrosis factor(TNF)-α, interferon(IFN)-γ, interleukin (IL)-6, and decreased that for IL-10 in the colon of DSS colitis. In contrast, tranilast markedly decreased expression of mRNAs for the proinflammatory cytokines, and increased that of the anti-inflammatory cytokines. Moreover, tranilast increased HO-1 expression on colonic epithelial cells as well as on colon infiltrating cells of DSS colitis. CONCLUSION: Tranilast ameliorated DSS colitis by regulating mast cell degranulation, decreasing inflammatory cytokines and increasing anti-inflammatory cytokines. Tranilast might exert these effects partly through enhanced HO-1 expression in the colon, suggesting a potential adjunctive therapy for IBD.

T1268 Gut Bio-Regulation in Health and Disease: Fermentonomic Insights – A Pilot Study

Background: Resident colonic bacteria, principally anaerobes and firmicutes, ferment undigested fibre, leading to the formation of volatile organic compounds (VOC). These are passed in faeces but also possibly absorbed and excreted in the urine. We hypothesised that the “fermentation profile” (FP), as seen in faeces and urine, may differ in health and in inflammatory bowel disease (IBD), and in the latter may change as the patient responds to treatment. Aim: Pilot study to determine if FP in faeces and urine can be recognised and reliably measured and to examine if there were identifiable differences in health and IBD. Methods: Healthy volunteers n=2; Longitudinal study of IBD patients: ulcerative colitis (UC) n=1, studied when acutely ill and when better on treatment; Crohn's disease (CD) n=1, at the beginning and during the course of Infliximab therapy. Samples of faeces and urine were analysed fresh and after storage for 2 weeks. VOC were released by heating (thermal desorption, TD) separated by gas chromatography (GC) and identified by mass spectroscopy (MS). The noise in GC data was cleaned using Clearview software ©Markes. Results: Initial technical developments were made using horse, cow and chicken faeces: each showed a very large number of peaks, some shared. Volunteers within-run variability: <15% for faeces but <10% for urine, reflecting its more uniform nature. Data from urine VOC is presented here. All individuals showed a wide range of peaks, which could be grouped into 5 broad categories (expressed as % of total compounds present). IBD patients showed higher levels of TAK but lower levels of TOA. The IBD VOC profile changed with improvement on treatment: CD: HB Index fell from 4 to 0 at week 6; the TOA and PG levels fluctuated. UC: SCA Index fell from 4 to 3; VOC profile showed changes similar to those in CD and in addition, loss of high molecular weight compounds. Conclusion: We have observed: 1 Clear differences in VOC profiles between healthy volunteers and IBD patients 2 Improvement in IBD during treatment was associated with change in VOC profile. We believe the study of FPs using TD-GC/MS offers new insights into gut health which have clinical relevance.

S1743 Myosin Light Chain Kinase is Associated With Disruption of Epithelial Tight Junction in Colitis-Associated Tumor

BACKGROUND: Mast cells play a key role in the pathophysiology of inflammatory bowel disease (IBD). Tranilast, N-(3,4-dimethoxycinnamoyl) anthranilic acid, a mast cell stabilizer, has been empirically used for IBD in Japan. The mechanism of tranilast in the improvement of IBD, however, has not yet been clearly delineated, and requires further investigation. Recently, heme oxygenase (HO)-1 has attracted attention in the pro-inflammationmechanism of tranilast. Aim: To investigate the role of tranilast for the treatment of IBD, and elucidated the mechanism and involvement of HO-1 in this effect, we administered tranilast intrarectally to dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: Colitis was induced in C57BL/6(B6) mice by adding 3% DSS in drinking water ad libium for 5 days. Tranilast was administered by enema on day 0, day 2, and day 4 after induction of colitis. The disease activity index (DAI) and degree of colon injury were determined to know the clinical course of colitis. Toluidine blue staining was carried out to identify the mast cell. Staining for HO1 with immunofluorescence to evaluate the expression of HO-1 in the colon. Total RNA was extracted from colon specimens with quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Tranilast ameliorated DSS colitis clinically and pathologically with decreased number and degranulation of mast cells in the colon of DSS colitis. mRNA expression was increased for tumor necrosis factor(TNF)-α, interferon(IFN)-γ, interleukin (IL)-6, and decreased that for IL-10 in the colon of DSS colitis. In contrast, tranilast markedly decreased expression of mRNAs for the proinflammatory cytokines, and increased that of the anti-inflammatory cytokines. Moreover, tranilast increased HO-1 expression on colonic epithelial cells as well as on colon infiltrating cells of DSS colitis. CONCLUSION: Tranilast ameliorated DSS colitis by regulating mast cell degranulation, decreasing inflammatory cytokines and increasing anti-inflammatory cytokines. Tranilast might exert these effects partly through enhanced HO-1 expression in the colon, suggesting a potential adjunctive therapy for IBD.

P.174 DIAGNOSTIC ROLE OF CAPSULE ENDOSCOPY IN PATIENTS WITH SYMPTOMS HIGHLY COMPATIBLE WITH CROHN'S DISEASE

Background: Resident colonic bacteria, principally anaerobes and firmicutes, ferment undigested fibre, leading to the formation of volatile organic compounds (VOC). These are passed in faeces but also possibly absorbed and excreted in the urine. We hypothesised that the “fermentation profile” (FP), as seen in faeces and urine, may differ in health and in inflammatory bowel disease (IBD), and in the latter may change as the patient responds to treatment. Aim: Pilot study to determine if FP in faeces and urine can be recognised and reliably measured and to examine if there were identifiable differences in health and IBD. Methods: Healthy volunteers n=2; Longitudinal study of IBD patients: ulcerative colitis (UC) n=1, studied when acutely ill and when better on treatment; Crohn's disease (CD) n=1, at the beginning and during the course of Infliximab therapy. Samples of faeces and urine were analysed fresh and after storage for 2 weeks. VOC were released by heating (thermal desorption, TD) separated by gas chromatography (GC) and identified by mass spectroscopy (MS). The noise in GC data was cleaned using Clearview software ©Markes. Results: Initial technical developments were made using horse, cow and chicken faeces: each showed a very large number of peaks, some shared. Volunteers within-run variability: <15% for faeces but <10% for urine, reflecting its more uniform nature. Data from urine VOC is presented here. All individuals showed a wide range of peaks, which could be grouped into 5 broad categories (expressed as % of total compounds present). IBD patients showed higher levels of TAK but lower levels of TOA. The IBD VOC profile changed with improvement on treatment: CD: HB Index fell from 4 to 0 at week 6; the TOA and PG levels fluctuated. UC: SCA Index fell from 4 to 3; VOC profile showed changes similar to those in CD and in addition, loss of high molecular weight compounds. Conclusion: We have observed: 1 Clear differences in VOC profiles between healthy volunteers and IBD patients 2 Improvement in IBD during treatment was associated with change in VOC profile. We believe the study of FPs using TD-GC/MS offers new insights into gut health which have clinical relevance.

Hematopoietic stem cell transplantation in a CD3γ‐deficient infant with inflammatory bowel disease

Partial or total CD3 chain expression defects including CD3 gamma, epsilon, delta, and zeta chain are among the autosomally inherited SCID presenting with T-B+NK+ phenotype with lymphopenia. The clinical findings are generally severe in all except for CD3 gamma deficiency. Here we present a 10-month-old CD3 gamma deficient boy with IBD. The patient had suffered from intractable diarrhea, recurrent pulmonary infections and oral moniliasis since two months of age. Following the first allogeneic HSCT from his HLA-identical (6/6) sister after a reduced intensity regimen, a second transplantation was performed five months later. On day +19 after second transplantation, the CD3 TCR alpha/beta chain expression increased to 66% with development of full donor chimerism (98.6%). A significant improvement in diarrhea, perianal lesions, and rectal fistula was observed suggesting an improvement in inflammatory bowel disease. The patient died at home on day +50 with a sudden respiratory failure secondary to an undetermined infection. The case was interesting being the first reported case with SCID and inflammatory bowel disease who responded very well to HSCT by full recovery of intractable diarrhea, failure to thrive, laboratory findings, and improvement of fistula formation.

On the action of methotrexate and 6-Mercaptopurine on M. avium subspecies paratuberculosis

Clinical improvement in inflammatory bowel disease (IBD) treated with methotrexate and 6-mercaptopurine (6-MP) is associated with a decrease in proinflammatory cytokines. This has been presumed to indicate the “anti-inflammatory” mechanism of action of methotrexate and 6-MP. Although controversial, there are increasingly compelling data that Mycobacterium avium subspecies paratuberculosis (MAP) may be an etiological agent in some or all of IBD. We hypothesized that the clinical efficacy of methotrexate and 6-MP in IBD may be to simply inhibit the growth of MAP. The effect on MAP growth kinetics by methotrexate and 6-MP were evaluated in culture of two strains each of MAP (ATCC 19698 [bovine] & Dominic [human]) and M. avium (ATCC 28291 & 101) using a radiometric (14CO2 BACTEC®) detection system that quantifies mycobacterial growth as arbitrary “growth index units” (GI.) Efficacy data are presented as “percent decrease in cumulative GI” (%-ΔcGI.) The positive control was clarithromycin (a macrolide with excellent coverage against MAP) the negative was the β lactam, ampicillin, which has no clinical role in the therapy of human mycobacterial diseases. With ATCC 19698 the positive control antibiotic, clarithromycin exhibits ≥ 86 %-ΔcGI at the lowest concentration evaluated (0.5 μg/ml). The negative control antibiotic ampicillin has a trivial (21%-ΔcGI) at 32 μg/ml. In contrast, 6-MP has an initial ≥ 43%-ΔcGI starting at 1μg/ml that is ≥ 84 % -ΔcGI at 4 μg/ml. Methotrexate has 40%-ΔcGI inhibition at 2 mg/ml and ≥75%-ΔcGI at 4μg/ml. With Dominic, methotrexate has ≥88%-ΔcGI by 4μg. In the other three isolates, although far more effective than ampicillin, 6-MP is consistently less effective than methotrexate in %-ΔcGI. We show that methotrexate and 6-MP inhibit MAP growth in vitro. Each of the four isolates manifests different %-ΔcGI. These data are compatible with the hypothesis that the clinical improvement in patients with IBD treated with methotrexate and 6-MP could be due to treating a MAP infection. The decrease in proinflammatory cytokines, thought to be the primary mechanism of action, may simply be a normal, secondary, physiological response. Antibiotic resistance, because of lack of appropriate poly antimycobacterial therapy may account for variation in response to antiMAP agents in IBD and be associated with clinical exacerbations such as toxic megacolon. We conclude that henceforth, in clinical studies that evaluate the effect of anti-MAP agents in IBD, the use of methotrexate and 6-MP should be excluded from any control or “placebo” groups.

On the Action of Methotrexate and 6-Mercaptopurine on M. avium Subspecies paratuberculosis

BackgroundClinical improvement in inflammatory bowel disease (IBD) treated with methotrexate and 6-mercaptopurine (6-MP) is associated with a decrease in pro-inflammatory cytokines. This has been presumed to indicate the mechanism of action of methotrexate and 6-MP. Although controversial, there are increasingly compelling data that Mycobacterium avium subspecies paratuberculosis (MAP) may be an etiological agent in some or all of IBD. We hypothesized that the clinical efficacy of methotrexate and 6-MP in IBD may be to simply inhibit the growth of MAP.MethodologyThe effect on MAP growth kinetics by methotrexate and 6-MP were evaluated in cell culture of two strains each of MAP and M. avium using a radiometric (14CO2 BACTEC®) detection system that quantifies mycobacterial growth as arbitrary “growth index units” (GI). Efficacy data are presented as “percent decrease in cumulative GI” (% −ΔcGI).Principal FindingsThe positive control antibiotic (clarithromycin) has ≥85% −ΔcGI at a concentration of 0.5 µg/ml. The negative control (ampicillin) has minimal inhibition at 64 µg/ml. MAP ATCC 19698 shows ≥80% −ΔcGI for both agents by 4 µg/ml. With the other three isolates, although more effective than ampicillin, 6-MP is consistently less effective than methotrexate.ConclusionsWe show that methotrexate and 6-MP inhibit MAP growth in vitro. Each of the four isolates manifests different % −ΔcGI. These data are compatible with the hypothesis that the clinical improvement in patients with IBD treated with methotrexate and 6-MP could be due to treating a MAP infection. The decrease in pro-inflammatory cytokines, thought to be the primary mechanism of action, may simply be a normal, secondary, physiological response. We conclude that henceforth, in clinical studies that evaluate the effect of anti-MAP agents in IBD, the use of methotrexate and 6-MP should be excluded from any control groups.

Improvement of inflammatory bowel disease after allogeneic stem-cell transplantation.

Because causes of inflammatory bowel disease (IBD) remain obscure and a curative therapy is still lacking, the influence of stem-cell transplantation (SCT) on IBD is of major interest. We retrospectively analyzed the course of seven patients with Crohn's disease and four patients with idiopathic ulcerative colitis who underwent allogeneic SCT between July 1994 and August 2002 for acute and chronic myeloid leukemia and myelodysplastic syndrome. After a median follow-up of 34 months posttransplantation, 10 patients are alive. None of the patients showed IBD activity after SCT, except one patient with mild persistent symptoms of Crohn's disease early after transplant. Colonoscopy after complete discontinuation of prophylactic posttransplant immunosuppression revealed no pathologic findings. These observations imply that host immune dysregulation plays a central role in the perpetuation of IBD. It may be influenced by the implementation of a new allogeneic immune system resulting from the transplantation of hematopoietic stem cells.

Preliminary experience with plasma exchange in patients with ulcerative colitis

We decided to test the effect of plasma exchange (PE) in selected patients with inflammatory bowel disease in which conventional medical treatment proved insufficient. Twenty-six patients with ulcerative colitis (UC) were treated with PE, six patients with fulminant colitis and 20 with long lasting severe colitis. After very promising results initially, 17 patients with long lasting severe colitis were selected in a careful prospective study. Twelve patients completed the treatment protocol. Two litres of plasma were exchanged every second or third day, 5–6 times in two weeks. The replacement fluid was fresh frozen plasma. The activity indices and histological evaluation were used as criteriae for treatment response. A reduction of 35% in the activity index is considered a significant improvement. In all but three patients (out of 12), the activity indices were reduced two weeks after end of treatment. Six patients had a reduction of more than 35%, three patients had a reduction between 22–28% and three had a reduction less than 10%. None became worse. In this carefully studied group, the immediate beneficial effects of PE was only demonstrable by the activity indices and not evident by blind evaluation of biopsies from the mucosa. In two of the six patients with fulminant colitis, PE was followed by an immediate dramatic clinical improvement. In the follow up period (2–14 years) 14 of the 26 patients reported marked and long lasting improvement of inflammatory bowel disease. We conclude that PE might be beneficial in subsets of patients with UC.