Ulcerative Colitis: Louis E

Melange M, D'Haens G, Devos M, Kartheuser A, Louis E, Pattyn P, Pelckmans P, Penninckx F, Potvin P, Schapira M, Van de Stadt J, Van Gossum AV, Anonymous00094. · No affiliation provided · Acta Gastroenterol Belg. · Pubmed #11189986 No free full text.

This publication has no abstract.

Belaiche J, Chapelier N, Wertz S, Louis E. · Service d'Hépato-Gastroentérologie, CHU Sart Tilman, Liège, Belgique. · Rev Med Liege. · Pubmed #18214363 No free full text.

Abstract: Inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis are frequent illnesses in western countries. They have a dramatic impact on the health-related quality of life. The new biological treatments developed for these diseases are potentially very effective, but are also expensive and may have significant side effects. In the present paper, the authors describe new biological therapies used during the past 10 years at the CHU. More than 20 therapeutic protocols were implemented. These protocols have given the patients the opportunity to gain very rapid access to new efficient therapies, to benefit from promising techniques for the evaluation of their pathology and to be submitted to a close follow-up that frequently called their treatment into question in the light of the most innovative options.

Baert F, De Vos M, Louis E, Vermeire S, Anonymous00134. · Department of Gastroenterology, University Hospital Leuven, Herestraat 49, 3000 Leuven, Belgium. · Acta Gastroenterol Belg. · Pubmed #17715629 No free full text.

Abstract: BACKGROUND: The introduction of infliximab has greatly advanced the therapeutic armamentarium of the inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. Although the benefit/risk ratio for infliximab is positive, of particular concern has been the problem of immunogenicity ascribed to the chimeric properties of the drug. Antibody formation is associated with allergic reactions and loss of response. AIMS AND METHODS: A literature search was undertaken on the magnitude of the problem of immunogenicity and on the clinical consequences. A survey was conducted about the clinical practice and management of acute and delayed allergic reactions to infliximab in different centres in Belgium. For this, a questionnaire was sent to all members of the Belgian IBD research group (n = 38 belonging to 29 centers). RESULTS AND CONCLUSION: Infusion reactions are important immunologic events induced by the presence of a substantial concentration of antibodies against infliximab (ATI) in the serum. Concomitant immunosuppressive treatment may optimize response to infliximab by preventing the formation of antibodies. Steroid administration prior to an infliximab infusion can further reduce the immunogenicity. Probably the most effective strategy to optimize treatment and avoid immunogenicity is maintenance therapy. If infliximab therapy can be discontinued is yet unclear but when treatment goals have been reached, we feel this should be attempted. In the case of relapse, infliximab should be restarted as maintenance long term. Practical guidelines on how to handle the problem of immunogenicity to infliximab are important for clinicians treating patients with IBD.

Louis E, Belaiche J. · Service de Gastroentérologie, CHU de Liège, Belgium. · Acta Gastroenterol Belg. · Pubmed #10692777 No free full text.

Abstract: Azathioprine and 6-mercaptopurine are effective drugs in the management of steroid dependent and chronic active inflammatory bowel diseases. They are also well tolerated on the long term. However, their use is still hampered by some drawbacks including delay before efficacy, 20-35% of non responders, relapse at withdrawal of the drugs, possible bone marrow toxicity and other side effects. During the last few years, these drawbacks have been challenged by important studies showing that a better knowledge of the metabolism of these drugs may help to improve their use.

Dideberg V, Kristjansdottir G, Milani L, Libioulle C, Sigurdsson S, Louis E, Wiman AC, Vermeire S, Rutgeerts P, Belaiche J, Franchimont D, Van Gossum A, Bours V, Syvänen AC. · Department of Human Genetics, CHU de Liège, Belgium. · Hum Mol Genet. · Pubmed #17881657 links to  free full text

Abstract: The interferon regulatory factor 5 (IRF5) gene encodes a transcription factor that plays an important role in the innate as well as in the cell-mediated immune responses. The IRF5 gene has been shown to be associated with systemic lupus erythematosus and rheumatoid arthritis. We studied whether the IRF5 gene is also associated with inflammatory bowel diseases (IBD), Crohn disease (CD) and ulcerative colitis (UC). Twelve polymorphisms in the IRF5 gene were genotyped in a cohort of 1007 IBD patients (748 CD and 254 UC) and 241 controls from Wallonia, Belgium. The same polymorphisms were genotyped in a confirmatory cohort of 311 controls and 687 IBD patients (488 CD and 192 UC) from Leuven, Belgium. A strong signal of association [P = 1.9 x 10(-5), odds ratio (OR) 1.81 (1.37-2.39)] with IBD was observed for a 5 bp indel (CGGGG) polymorphism in the promoter region of the IRF5 gene. The association was detectable also in CD patients (P = 6.8 x 10(-4)) and was particularly strong among the UC patients [P = 5.3 x 10(-8), OR = 2.42 (1.76-3.34)]. The association of the CGGGG indel was confirmed in the second cohort [P = 3.2 x 10(-5), OR = 1.59 (1.28-1.98)]. The insertion of one CGGGG unit is predicted to create an additional binding site for the transcription factor SP1. Using an electrophoretic mobility shift assay, we show allele-specific differences in protein binding to this repetitive DNA-stretch, which suggest a potential function role for the CGGGG indel.

De Jager PL, Franchimont D, Waliszewska A, Bitton A, Cohen A, Langelier D, Belaiche J, Vermeire S, Farwell L, Goris A, Libioulle C, Jani N, Dassopoulos T, Bromfield GP, Dubois B, Cho JH, Brant SR, Duerr RH, Yang H, Rotter JI, Silverberg MS, Steinhart AH, Daly MJ, Podolsky DK, Louis E, Hafler DA, Rioux JD, Anonymous00242, Anonymous00243. · Department of Neurology, Center for Neurologic Diseases, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA. · Genes Immun. · Pubmed #17538633 No free full text.

Abstract: The intestinal flora has long been thought to play a role either in initiating or in exacerbating the inflammatory bowel diseases (IBD). Host defenses, such as those mediated by the Toll-like receptors (TLR), are critical to the host/pathogen interaction and have been implicated in IBD pathophysiology. To explore the association of genetic variation in TLR pathways with susceptibility to IBD, we performed a replication study and pooled analyses of the putative IBD risk alleles in NFKB1 and TLR4, and we performed a haplotype-based screen for association to IBD in the TLR genes and a selection of their adaptor and signaling molecules. Our genotyping of 1539 cases of IBD and pooled analysis of 4805 cases of IBD validates the published association of a TLR4 allele with risk of IBD (odds ratio (OR): 1.30, 95% confidence interval (CI): 1.15-1.48; P=0.00017) and Crohn's disease (OR: 1.33, 95% CI: 1.16-1.54; P=0.000035) but not ulcerative colitis. We also describe novel suggestive evidence that TIRAP (OR: 1.16, 95% CI: 1.04-1.30; P=0.007) has a modest effect on risk of IBD. Our analysis, therefore, offers additional evidence that the TLR4 pathway - in this case, TLR4 and its signaling molecule TIRAP - plays a role in susceptibility to IBD.

Meuwis MA, Fillet M, Geurts P, de Seny D, Lutteri L, Chapelle JP, Bours V, Wehenkel L, Belaiche J, Malaise M, Louis E, Merville MP. · Laboratory of Clinical Chemistry, GIGA Research, CHU, University of Liège, B34, 4000 Liège, Belgium. · Biochem Pharmacol. · Pubmed #17258689 No free full text.

Abstract: Crohn's disease and ulcerative colitis known as inflammatory bowel diseases (IBD) are chronic immuno-inflammatory pathologies of the gastrointestinal tract. These diseases are multifactorial, polygenic and of unknown etiology. Clinical presentation is non-specific and diagnosis is based on clinical, endoscopic, radiological and histological criteria. Novel markers are needed to improve early diagnosis and classification of these pathologies. We performed a study with 120 serum samples collected from patients classified in 4 groups (30 Crohn, 30 ulcerative colitis, 30 inflammatory controls and 30 healthy controls) according to accredited criteria. We compared protein sera profiles obtained with a Surface Enhanced Laser Desorption Ionization-Time of Flight-Mass Spectrometer (SELDI-TOF-MS). Data analysis with univariate process and a multivariate statistical method based on multiple decision trees algorithms allowed us to select some potential biomarkers. Four of them were identified by mass spectrometry and antibody based methods. Multivariate analysis generated models that could classify samples with good sensitivity and specificity (minimum 80%) discriminating groups of patients. This analysis was used as a tool to classify peaks according to differences in level on spectra through the four categories of patients. Four biomarkers showing important diagnostic value were purified, identified (PF4, MRP8, FIBA and Hpalpha2) and two of these: PF4 and Hpalpha2 were detected in sera by classical methods. SELDI-TOF-MS technology and use of the multiple decision trees method led to protein biomarker patterns analysis and allowed the selection of potential individual biomarkers. Their downstream identification may reveal to be helpful for IBD classification and etiology understanding.

Van Gossum A, Dewit O, Louis E, de Hertogh G, Baert F, Fontaine F, DeVos M, Enslen M, Paintin M, Franchimont D. · Erasme University Hospital, ULB, Brussels, Belgium. · Inflamm Bowel Dis. · Pubmed #17206696 links to  free full text

Abstract: BACKGROUND: Seventy percent of Crohn's disease (CD) patients exhibit anastomotic recurrence within 1 year after ileo-caecal surgery. Recent clinical trials suggest the beneficial use of probiotics in the control of intestinal inflammation in pouchitis and ulcerative colitis. This study is a multicenter clinical trial evaluating the efficacy of an oral administration of the probiotic LAl on early post-operative endoscopic recurrence of CD. METHODS: Seventy patients with CD were enrolled prior to elective ileo-caecal resection and randomly assigned after surgery to daily treatment with either Lactobacillus johnsonii, LA1, Nestle (1010 colony-forming units, CFU) (group A, n = 34) or placebo (group B, n = 36) for 12 weeks. The primary objective was to assess the effect of LAl on the endoscopic recurrence rate at 12 weeks. Stratification was performed according to smoking status at randomization. RESULTS: Seven and 14 patients were excluded in the LA1 and placebo groups, respectively. In intention-to-treat analysis, the mean endoscopic score was not significantly different between the two treatment groups at 3 months (LA1 versus placebo: 1.50 +/- 1.32 versus 1.22+/-1.37, treatment effect: P = 0.48, smoke effect: P = 0.72). The percentage of patients with severe recurrence (i3 + i4) was 21% and 15% in the LAl and placebo groups, respectively (P = 0.33). Using a per-protocol (PP) analysis, the mean endoscopic score was not significantly different between the two treatment groups (LAl versus placebo groups: 1.44 +/-1.31 versus 1.05 +/- 1.21, P = 0.32). The percentage of patients with severe recurrence (i3 + i4) was 19% and 9% in the LAl and placebo groups, respectively (P = 0.054). Clinical relapse rate (CDAI [CD activity index] > 150, with an increase of CDAI > 70 points or greater from baseline) in the LAl and placebo groups was 15% (4/27) and 13.5% (3/22), respectively (PP analysis: chi-square test, P = 0.91 and log-rank test: P = 0.79). CONCLUSION: Oral administration of the probiotic LA1 in patients with CD failed to prevent early endoscopic recurrence at 12 weeks after ileo-caecal resection.

Daniel F, Loriot MA, Seksik P, Cosnes J, Gornet JM, Lémann M, Fein F, Vernier-Massouille G, De Vos M, Boureille A, Treton X, Flourié B, Roblin X, Louis E, Zerbib F, Beaune P, Marteau P. · Department of Gastroenterology, Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou, Paris, France. · Inflamm Bowel Dis. · Pubmed #17206635 links to  free full text

Abstract: BACKGROUND: Cyclosporine A (CsA) is inconstantly effective in inducing remission in acute attacks of ulcerative colitis (UC) not responding to steroids. This study aimed to establish whether multidrug resistance gene (MDR)1 polymorphisms would be associated with CsA failure. PATIENTS AND METHODS: The distribution of the different genotypes of single nucleotide polymorphisms (SNP) G2677T/A and C3435T of MDR1 exons 21 and 26, respectively, was studied in 154 patients (mean age, 44 yr) who had received CsA to treat severe attacks of steroid resistant UC in 11 centers in France and Belgium. Patients were classified as CsA failure (n = 50) when they needed colectomy within 30 days after CsA initiation. The SNPs were detected by use of a 5' nuclease allelic discrimination assay. RESULTS: There was a significant association between the G2677T/A polymorphism distribution (exon 21) and the risk for CsA failure (P = 0.0001). The TT genotype of exon 21 was significantly associated with the risk compared with the two other genotypes (odds ratio, 3.77; 95% confidence interval, 1.42-9.97, P = 0.007). There was no significant association between the genotype C3435T distribution (exon 26) and the risk of CsA failure (P = 0.23). CONCLUSION: The TT genotype of exon 21 MDR1 polymorphisms is associated with a higher risk of CsA failure in patients with steroid resistant UC. Further studies should be performed to establish whether other treatments could be more efficient to avoid surgery in this subset of patients.

Vijverman A, Piront P, Belaiche J, Louis E. · Department of gastroenterology, CHU of Liège, Belgium. · Acta Gastroenterol Belg. · Pubmed #16673554 No free full text.

Abstract: INTRODUCTION: Anemia has been considered as an overlooked complication of inflammatory bowel disease. Studies dating back to the 80ties and the 90ties have shown 30% of anemia among inflammatory bowel disease (IBD) patients. More recently, the broader use of immunosuppressive drug and infliximab allowing better mucosal healing as well as a more aggressive treatment of anemia, including the use of safer form of IV iron, may have influenced the prevalence of anemia among IBD patients. Our aim was to asses the prevalence and characteristics of anemia among two cohorts of IBD patients at 10 years interval and to look for associated clinical or demographic factors. METHODS: Using the IBD patients register of one senior gastroenterologist, we identified IBD patients he had consecutively seen and who had blood test at the outpatient clinic during the years 1993 and 2003. Demographic and clinical characteristics, treatment for Crohn's disease, blood test results and treatment of anemia were recorded and compared between these two cohorts. Anemia was defined as an hemoglobin level lower than the normal value of the laboratory of our hospital. RESULTS: 80 and 90 patients were identified in 1993 and 2003, respectively. There was no significant difference between the two cohorts, according to age, gender, disease type, duration or location. There were 27/80 (33.8%) and 15/90 (16.7%) anemic patients in 1993 and 2003, respectively (P = 0.013). The prevalence of severe anemia (hemoglobin level < 10.5 g/100 ml) was similar in the two cohorts (6.3% and 5.6%). Characteristics of the anemia were similar in the two cohorts with a majority of iron deficiency anemia and inflammatory anemia. Ferritin and CRP levels were not significantly different in the two cohorts. The only significant difference was a more frequent use of immunosuppressive treatment and infliximab in 2003 than in 1993 (33.3% vs. 13.8% ; P = 0.0038, RR: 0.41, 0.22-0.77) CONCLUSIONS: Prevalence of mild to moderate anemia has significantly decreased in our population over the last 10 years. The only difference detected between the two cohorts was the increased use of immunosuppressive drug (mainly azathioprine).

Gustot T, Lemmers A, Louis E, Nicaise C, Quertinmont E, Belaiche J, Roland S, Van Gossum A, Devière J, Franchimont D. · Division of Gastroenterology, Erasme University Hospital, Free University of Brussels, 808 Lennik St, 1070 Brussels, Belgium. · Gut. · Pubmed #15753533 links to  free full text

Abstract: INTRODUCTION: Soluble cytokine receptors (sCRs) modulate the in vivo activity of cytokines. Deficient sCR production could participate in the pathogenesis and course of Crohn's disease (CD). The aim of the study was to examine the profile of sCRs in CD patients and their modulation by infliximab and corticosteroids. METHODS: We prospectively examined active CD patients (aCD) treated with either infliximab (n = 21) or corticosteroids (n = 9), CD patients in clinical remission (rCD, n = 20), ulcerative colitis patients (UC, n = 24), and healthy subjects (HS, n = 15). Cultures of colonic biopsies were also examined from CD inflamed (n = 8), CD non-inflamed (n = 7), and healthy mucosa (n = 8). Levels of tumour necrosis factor alpha (TNF-alpha), soluble TNF receptor I (sTNFRI), soluble TNF receptor II (sTNFRII), interleukin 1beta (IL-1beta), soluble IL-1 receptor I (sIL-1RI), soluble IL-1 receptor II (sIL-1RII), IL-6, soluble IL-6 receptor (sIL-6R), and sgp130 were measured using ELISA. RESULTS: Higher levels of sTNFRI (p<0.05, p<0.01), sTNFRII (p<0.01, p<0.01), sIL-1RI (p<0.05, NS), IL-6 (p<0.01, p<0.01), and sIL-6R (p<0.05, NS) were observed in aCD compared with rCD and HS. Interestingly, sIL-1RII (p<0.05, p<0.01) and sgp130 (p<0.01, p<0.01) were profoundly decreased in aCD compared with rCD and HS, and were negatively correlated with CRP. Deficient production of sIL-1RII was specific to CD (not observed in ulcerative colitis), and was further confirmed at the mucosal level. Infliximab decreased sTNFRII at one and four weeks (p<0.05) and enhanced sIL-6R levels at one week (p<0.05). Corticosteroids increased sIL-1RII levels at one week (p<0.05). CONCLUSION: CD is associated with dysregulated production of sCRs. Deficiency in sIL-1RII and sgp130 may be essential to CD pathogenesis. Their replacement through the use of fusion proteins could represent future alternative therapeutic strategies for CD.

El Yafi F, Winkler R, Delvenne P, Boussif N, Belaiche J, Louis E. · Department of Gastroenterology, CHU of Liège, Liège, Belgium. · Clin Exp Immunol. · Pubmed #15730399 links to  free full text

Abstract: The fibrotic and antiapoptotic effects of insulin-like growth factors (IGF) are mediated by type I IGF receptor (IGF-1R). IGFs could play a role in intestinal stricturing and in the maintenance of inflammation in Crohn's disease (CD). We aimed to describe IGF-1R expression in CD intestinal lesions, to compare it to other intestinal inflammatory diseases and to correlate it with fibrosis and apoptosis. IGF-1R expression and apoptosis (active caspase-3) were studied by immunohistochemistry. Surgical intestinal specimens [17 CD, nine controls, six diverticulitis and four ulcerative colitis (UC)] were used. IGF-1R was expressed transmurally mainly by inflammatory cells (IC) and smooth muscle cells, both in diseased intestine and controls. IGF-1R positive IC were increased in the mucosa and the submucosa of CD (P < 0.007), and in involved areas compared to uninvolved areas (P = 0.03). In UC, the number of IGF-1R positive IC was only increased in the mucosa, and was not different from controls in the submucosa. In diverticulitis, the number of IGF-1R positive IC did not differ from controls. In CD submucosa, IGF-1R expression in IC was inversely correlated with apoptosis in uninvolved areas (P = 0.01). Expression of IGF-1R in submucosal fibroblast-like cells, subserosal adipocytes and hypertrophic nervous plexi was specific for CD. We have shown a transmural altered expression of IGF-1R in CD. This may suggest a role for IGF-1R in the maintenance of chronic inflammation and stricture formation in CD.

Van Assche G, Baert F, De Reuck M, De Vos M, De Wit O, Hoang P, Louis E, Mana F, Pelckmans P, Rutgeerts P, Van Gossum A, D'Haens G. · Department of Internal Medicine-Gastroenterology, UZ Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. · Acta Gastroenterol Belg. · Pubmed #12619425 No free full text.

Abstract: Aminosalicylates (5-ASA, sulfasalazine and mesalazine) play a central role in the treatment of ulcerative colitis (UC). For acute treatment of mild to moderate flares and in maintenance treatment, their efficacy has been established. Since ulcerative colitis is limited to the distal colon in two thirds of the patients, topical therapy also plays an important role. In mild/moderate active disease 5-ASA 4 g/d is as effective as oral corticosteroids. Ulcerative proctitis is treated with 2 x 500 mg or 1 x 1 g suppositories and proctosigmoiditis with 1 to 4 g enemas. Oral 5-ASA is also safe in maintenance treatment and is generally well tolerated. The risk of colorectal tumours is increased in patients with longstanding ulcerative colitis and epidemiological evidence indicates that chronic 5-ASA treatment reduces this risk. However, at present there is insufficient evidence to maintain patients on life-long 5-ASA maintenance treatment for this indication.

Piront P, Louis E, Latour P, Plomteux O, Belaiche J. · Service de Gastroentérologie, CHU of Liège, Belgique. · Gastroenterol Clin Biol. · Pubmed #11938067 links to  free full text

Abstract: OBJECTIVE: Inflammatory bowel diseases (IBD) are heterogeneous diseases which affect preferentially young adults. The late onset could represent a particular form of expression of these diseases. The aim of our prospective study was to describe the incidence of IBD in patients older than 60 years as well as their clinical pattern in comparison with a population younger than 60.METHODS: A standardized questionnaire for each new case diagnosed in the province of Liège between 01/06/1993 and 31/05/1996 was completed.RESULTS: During the three years, 270 patients were enrolled. In group IBD > 60 years old, there were 60 new cases, including 23 cases with Crohn's disease (CD) (38%), 30 with ulcerative colitis (UC) (50%), and 7 with undetermined colitis (IC) (12%). The proportion of CD was significantly lower in the group IBD > 60 years old than in the group<60 (114 CD (54%), 81 UC (39%) and 15 IC (7%); P=0.04).The annual incidence tended to be higher for UC than for CD in group IBD > 60 (4.5 and 3.5 per 100,000, respectively) while it was the contrary in younger patients (3.4 and 4.8 per 100,000, respectively). There was no striking difference in the clinical features for both diseases in the two groups, except more frequent diarrhea, weight loss and extraintestinal symptoms in CD patients<60 years old.CONCLUSIONS: In the province of Liège, the incidence of IBD in people older than 60 years is high. IBD in the elderly is characterized by a lower proportion of CD than in the younger population. Clinical features tend to be the same whatever the age at diagnosis for each disease.

Louis E. · Department of Gastroenterology, CEMIC (Centre d'Etude des Maladies Inflammatoires Chroniques), and CTCM (Centre de Thérapie Cellulaire et Moléculaire), University Hospital of Liège, Belgium. · Acta Gastroenterol Belg. · Pubmed #11322060 No free full text.

Abstract: Inflammatory bowel diseases are multifactorial polygenic diseases. The author has worked on the characterisation of the mucosal immuno-inflammatory reaction, on genetic predisposition and on potential clinical application of blood immuno-inflammatory markers in these diseases. This paper summarizes some aspects of this work, focusing on TNF. Following points are developed: production of TNF by inflamed mucosa, genetic control of TNF production, TNF gene polymorphim in inflammatory bowel disease, and evaluation of serum TNF as a marker of disease activity or evolutivity.

Belaiche J, Louis E. · Department of gastroenterology, CHU Sart-Tilman, 4000 Liège, Belgium. · Acta Gastroenterol Belg. · Pubmed #11189987 No free full text.

Abstract: Severe colitis is life-threatening complication of ulcerative colitis. Early recognition of the severity of the colitis, intensive medical therapy and prompt surgery when necessary have all contributed to improved outcome. Initial medical treatment should be instituted as soon as the diagnosis is made with an intravenous corticosteroid associated with supportive treatment. If the patient fails to response to this intensive treatment after 5-7 days, cyclosporin should be initiated. If cyclosporin is not used then colectomy should be performed immediately. Moreover, significant deterioration at any point during medical therapy is an indication for colectomy. The gravity of the patient's condition require close interaction between physician an surgeon.

Louis E, Ribbens C, Godon A, Franchimont D, De Groote D, Hardy N, Boniver J, Belaiche J, Malaise M. · Department of Gastroenterology, Inflammatory Diseases Research Group, and Department of Pathology, CHU, Liège, Belgium. · Clin Exp Immunol. · Pubmed #10792371 links to  free full text

Abstract: Inflammatory bowel diseases (IBD) are characterized by a sustained inflammatory cascade that gives rise to the release of mediators capable of degrading and modifying bowel wall structure. Our aims were (i) to measure the production of matrix metalloproteinase-3 (MMP-3), and its tissue inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), by inflamed and uninflamed colonic mucosa in IBD, and (ii) to correlate their production with that of proinflammatory cytokines and the anti-inflammatory cytokine, IL-10. Thirty-eight patients with IBD, including 25 with Crohn's disease and 13 with ulcerative colitis, were included. Ten controls were also studied. Biopsies were taken from inflamed and uninflamed regions and inflammation was graded both macroscopically and histologically. Organ cultures were performed for 18 h. Tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-1beta, IL-10, MMP-3 and TIMP-1 concentrations were measured using specific immunoassays. The production of both MMP-3 and the TIMP-1 were either undetectable or below the sensitivity of our immunoassay in the vast majority of uninflamed samples either from controls or from those with Crohn's disease or ulcerative colitis. In inflamed mucosa, the production of these mediators increased significantly both in Crohn's disease (P < 0.01 and 0.001, respectively) and ulcerative colitis (P < 0.001 and 0.001, respectively). Mediator production in both cases was significantly correlated with the production of proinflammatory cytokines and IL-10, as well as with the degree of macroscopic and microscopic inflammation. Inflamed mucosa of both Crohn's disease and ulcerative colitis show increased production of both MMP-3 and its tissue inhibitor, which correlates very well with production of IL-1beta, IL-6, TNF-alpha and IL-10.