Active Crohn's Colitis Research Articles

Eficacia y seguridad de vedolizumab en el tratamiento de la colitis ulcerosa

Integrins play a crucial role in the development and maintenance of the inflammatory process in patients with inflammatory bowel disease. Vedolizumab is a humanized monoclonal antibody with a predominantly gastrointestinal effect. It specifically inhibits leukocyte integrin α4β7, thus preventing its interaction with mucosal vascular addressin cell adhesion molecule 1(MAdCAM-1), which is involved in the migration of lymphocytes from the blood stream to the intestinal tissue. Vedolizumab is indicated in the treatment of moderate to severe active Crohn's disease and ulcerative colitis in adult patients with poor response, loss of response, or intolerance to conventional treatment or to tumour necrosis factor alpha (TNF-α) antagonists. This review presents the most relevant clinical outcomes of vedolizumab in the treatment of patients with ulcerative colitis.

Measles Vaccine Administered to a Crohnʼs Disease Patient Receiving Vedolizumab

Introduction: Patients with IBD on immunosuppressive therapy (ISS) with thiopurines, methotrexate or anti-TNF biologics are advised against receiving live virus vaccines due to concern about infections. In addition, it is known that there is an attenuated immune response to vaccines in patients receiving immune suppression. Vedolizumab is a gut-selective α4β7 anti- integrin monoclonal antibody approved by the FDA for the treatment of moderately to severely active Crohn's disease and ulcerative colitis. We report a case of a patient successfully vaccinated against measles virus while on vedolizumab therapy. Case Description: A 26 year old female with Crohn's ileocolitis was receiving vedolizumab and methotrexate 15 mg PO/week. She reported having received prior measles, mumps, rubella (MMR) vaccination in childhood. Due to a nation-wide measles resurgence, we assessed her measles titers to advise her of her risk of infection. Her measles antibody index (AI) was 0.7 (negative). We instructed her to stop the methotrexate and to continue the vedolizumab. Two weeks after stopping the methotrexate, she received the MMR vaccine. The methotrexate was restarted 4 weeks later. Measles AI 8 weeks after the MMR vaccine was 2.06 (positive). In 2 months follow up after she received the vaccine, there have been no adverse sequelae. Discussion: This case describes a novel approach to the MMR vaccination process in an IBD patient on vedolizumab with methotrexate. Although current guidelines state that MMR vaccine is contraindicated among immunocompromised IBD patients and should not be given to patients expected to start immunosuppressive agents within 6 weeks (1), these guidelines do not address organ-selective anti-integrin therapies. We believe that the gut-selective activity of vedolizumab allows for safe and effective administration of live virus vaccinations.Table 1: Summary of Measles IgG Antibody Index Before and After MMR Booster Administration

Characteristics of Patients Treated With Vedolizumab for Inflammatory Bowel Disease in the United States

Introduction: Vedolizumab (VDZ), a monoclonal antibody against the α4β7 integrin, has been approved for the treatment of adults with moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC) in the United States (US). Although few single-center experiences with VDZ have been described, reports from larger, nationally representative cohorts are limited. Using a large national administrative claims database, this retrospective study aims to describe the characteristics and treatment history of CD and UC patients initiating VDZ. Methods: Using the Optum Research Database, adults (≥18 years) initiating VDZ between May 2014 and February 2015, with at least 2 claims of CD or UC (based on ICD-9 criteria), ≥12 months of medical history (baseline) and ≥2 months of follow-up after the first VDZ infusion were included in the study cohort. Patients were assigned to the CD or UC cohort based on the diagnosis code on or closest to the first VDZ infusion date. Baseline demographic and clinical characteristics and treatment history at VDZ initiation are reported. Results: A total of 178 patients treated with VDZ were included in the study. The CD and UC cohorts included 122 (43% males) and 56 (59% males) patients, respectively. The mean age at VDZ initiation was 40 years (SD=14) for CD cohort and 43 years (SD=14) for UC cohort. In both cohorts, 92% patients were enrolled in a commercial health plan and 8% in Medicare Advantage plan. Most common baseline comorbid conditions were anemia (CD:48%, UC:46%), respiratory infections (CD:37%, UC:46%), skin disorders (CD:39%, UC:32%), connective tissue disease (CD:38%, UC:32%), and non-traumatic joint disorders (CD:36%, UC:29%). In the baseline period, IBD-related surgery was performed in 22% and 11% of CD and UC patients, respectively. The treatment history of patients at baseline is reported in Table 1.Table 1: Treatment History of Crohn's Disease (CD) and Ulcerative Colitis (UC) Patients at First Vedolizumab InfusionConclusion: In a large national database, more than two-thirds of patients initiating VDZ were in the CD cohort. Approximately one-third of CD and UC patients were biologic-naive in the past 12 months before VDZ initiation. A majority of the CD and UC patients initiating VDZ were exposed to biologic therapy in the previous year indicating that patients may have inadequate or suboptimal response or intolerance to their previous biologic therapy. Future studies describing real-world outcomes of VDZ in large CD and UC cohorts of both biologic-naive and biologic-exposed should be considered.

Pneumocystis pneumonia complicating immunosuppressive therapy in Crohns disease: A preventable problem?

We report the case of a 76-year-old man who presented with moderate active Crohn's colitis that was refractory to high-dose corticosteroids, mesalazine and 6-mercaptopurine. He subsequently received a trial of...

An investigation of fecal volatile organic metabolites in irritable bowel syndrome.

Diagnosing irritable bowel syndrome (IBS) can be a challenge; many clinicians resort to invasive investigations in order to rule out other diseases and reassure their patients. Volatile organic metabolites (VOMs) are emitted from feces; understanding changes in the patterns of these VOMs could aid our understanding of the etiology of the disease and the development of biomarkers, which can assist in the diagnosis of IBS. We report the first comprehensive study of the fecal VOMs patterns in patients with diarrhea-predominant IBS (IBS-D), active Crohn's disease (CD), ulcerative colitis (UC) and healthy controls. 30 patients with IBS-D, 62 with CD, 48 with UC and 109 healthy controls were studied. Diagnosis of IBS-D was made using the Manning criteria and all patients with CD and UC met endoscopic, histologic and/or radiologic criteria. Fecal VOMs were extracted by solid phase microextraction (SPME) and analyzed by gas chromatography-mass spectrometry (GC-MS). 240 VOMs were identified. Univariate analysis showed that esters of short chain fatty acids, cyclohexanecarboxylic acid and its ester derivatives were associated with IBS-D (p<0.05), while aldehydes were more abundant in IBD (p<0.05). A predictive model, developed by multivariate analysis, separated IBS-D from active CD, UC and healthy controls with a sensitivity of 94%, 96% and 90%; and a specificity of 82%, 80% and 80% respectively (p<0.05). The understanding of the derivation of these VOMs may cast light on the etiology of IBS-D and IBD. These data show that fecal VOMs analyses could contribute to the diagnosis of IBS-D, for which there is no laboratory test, as well as IBD.

Quantitative Metabolomic Profiling of Serum, Plasma, and Urine by 1H NMR Spectroscopy Discriminates between Patients with Inflammatory Bowel Disease and Healthy Individuals

Serologic biomarkers for inflammatory bowel disease (IBD) have yielded variable differentiating ability. Quantitative analysis of a large number of metabolites is a promising method to detect IBD biomarkers. Human subjects with active Crohn’s disease (CD) and active ulcerative colitis (UC) were identified, and serum, plasma, and urine specimens were obtained. We characterized 44 serum, 37 plasma, and 71 urine metabolites by use of 1H NMR spectroscopy and “targeted analysis” to differentiate between diseased and non-diseased individuals, as well as between the CD and UC cohorts. We used multiblock principal component analysis and hierarchical OPLS-DA for comparing several blocks derived from the same “objects” (e.g., subject) to examine differences in metabolites. In serum and plasma of IBD patients, methanol, mannose, formate, 3-methyl-2-oxovalerate, and amino acids such as isoleucine were the metabolites most prominently increased, whereas in urine, maximal increases were observed for mannitol, allantoin, xylose, and carnitine. Both serum and plasma of UC and CD patients showed significant decreases in urea and citrate, whereas in urine, decreases were observed, among others, for betaine and hippurate. Quantitative metabolomic profiling of serum, plasma, and urine discriminates between healthy and IBD subjects. However, our results show that the metabolic differences between the CD and UC cohorts are less pronounced.

Gastrointestinal infection as a trigger for inflammatory bowel disease

There is accumulating evidence on the importance of microbes in the development and maintenance of both the intestinal and immune systems. This review focuses on the current findings on the role of gastrointestinal pathogens in the cause of chronic inflammatory bowel disease. A number of intestinal pathogens including Mycobacterium avium subspecies paratuberculosis, adherent-invasive Escherichia coli, and Campylobacter species are associated at fairly high prevalence with Crohn's disease, while two recent studies found a low prevalence for cytomegalovirus. In a prospective study, M. avium subspecies paratuberculosis detection in early Crohn's disease was low and comparable to controls, while much higher in an established inflammatory bowel disease cohort. In the pediatric setting, a high prevalence of Clostridium difficile was seen in both active and inactive Crohn's disease and ulcerative colitis patients. Some studies have speculated that Salmonella or Campylobacter infection may increase the risk of inflammatory bowel disease on long-term follow-up, but detection bias was found to obscure the risk. Recent studies in mouse models have demonstrated that a combination of factors, including viral pathogens, genetic susceptibility, and commensal microflora, can lead to intestinal pathology. No evidence for causation of inflammatory bowel disease by a single agent has been found, whereas a number of microbes have been strongly associated with the presence of disease. The majority of recent studies support a role for the ability of intestinal pathogens to promote chronic inflammation in individuals with genetic susceptibility and/or other environmental factors which remain to be identified. These factors may include subsets of commensal microflora.

Role of the Gut in Visceral Fat Inflammation and Metabolic Disorders

Role of the Gut in Visceral Fat Inflammation and Metabolic Disorders

Expression of CD4+ forkhead box P3 (FOXP3)+ regulatory T cells in inflammatory bowel disease

Forkhead box P3 (FOXP3) plays an important role in the development and function of CD4(+) regulatory T (Treg) cells. In this study the percentage of CD4(+) FOXP3(+) Treg cells in peripheral blood mononuclear cells (PBMC) and the frequency of Treg cells in the colonic mucosa of patients with inflammatory bowel disease (IBD) were investigated. The percentage of CD4(+) FOXP3(+) Treg cells in PBMC was analyzed by flow cytometry. Immunohistochemistry was used to examine the FOXP3(+) cells in the inflamed mucosa. Real-time polymerase chain reaction and Western blot were used to detect the expressions of FOXP3 mRNA and protein in PBMC and mucosal biopsy specimens of IBD patients, respectively. Together with the decrease of percentage of Treg cells in PBMC, we found that the frequency of Treg cells increased significantly in inflamed mucosa of active or inactive Crohn's disease (CD) and ulcerative colitis (UC). The expressions of FOXP3 mRNA and protein increased in inflamed mucosa when compared with those in healthy controls, especially the FOXP3 mRNA in patients with active CD or UC. Interestingly, the expression of FOXP3 protein in active UC was higher than that in active CD. There was a decrease of CD4(+) FOXP3(+) Treg cells in peripheral blood and an accumulation of Treg cells in inflamed mucosa. These data suggested that the suppressive function of Treg cells may be partially inhibited and this could be an important factor in the recurrence of disease, especially in UC.

Lysozyme expression in microscopic colitis

AimsTo audit the cellular expression of the innate antibacterial enzyme lysozyme in colonic biopsies from a cohort of patients having microscopic colitis (MC—collagenous colitis (CC) or lymphocytic colitis (LC)). Results...

Mesalamine for Refractory Celiac Disease

Mesalamine for Refractory Celiac Disease

Molecular mechanism of glucocorticoid resistance in inflammatory bowel disease

Natural and synthetic glucocorticoids (GCs) are widely employed in a number of inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first-line treatment for inducing remission in moderate to severe active Crohn's disease and ulcerative colitis. Despite their extensive therapeutic use and the proven effectiveness, considerable clinical evidence of wide inter-individual differences in GC efficacy among patients has been reported, in particular when these agents are used in inflammatory diseases. In recent years, a detailed knowledge of the GC mechanism of action and of the genetic variants affecting GC activity at the molecular level has arisen from several studies. GCs interact with their cytoplasmic receptor, and are able to repress inflammatory gene expression through several distinct mechanisms. The glucocorticoid receptor (GR) is therefore crucial for the effects of these agents: mutations in the GR gene (NR3C1, nuclear receptor subfamily 3, group C, member 1) are the primary cause of a rare, inherited form of GC resistance; in addition, several polymorphisms of this gene have been described and associated with GC response and toxicity. However, the GR is not self-standing in the cell and the receptor-mediated functions are the result of a complex interplay of GR and many other cellular partners. The latter comprise several chaperonins of the large cooperative hetero-oligomeric complex that binds the hormone-free GR in the cytosol, and several factors involved in the transcriptional machinery and chromatin remodeling, that are critical for the hormonal control of target genes transcription in the nucleus. Furthermore, variants in the principal effectors of GCs (e.g. cytokines and their regulators) have also to be taken into account for a comprehensive evaluation of the variability in GC response. Polymorphisms in genes involved in the transport and/or metabolism of these hormones have also been suggested as other possible candidates of interest that could play a role in the observed inter-individual differences in efficacy and toxicity. The best-characterized example is the drug efflux pump P-glycoprotein, a membrane transporter that extrudes GCs from cells, thereby lowering their intracellular concentration. This protein is encoded by the ABCB1/MDR1 gene; this gene presents different known polymorphic sites that can influence its expression and function. This editorial reviews the current knowledge on this topic and underlines the role of genetics in predicting GC clinical response. The ambitious goal of pharmacogenomic studies is to adapt therapies to a patient's specific genetic background, thus improving on efficacy and safety rates.

Intestinal TM7 bacterial phylogenies in active inflammatory bowel disease

TM7 is a recently described subgroup of Gram-positive uncultivable bacteria originally found in natural environmental habitats. An association of the TM7 bacterial division with the inflammatory pathogenesis of periodontitis has been previously shown. This study investigated TM7 phylogenies in patients with inflammatory bowel diseases (IBDs). The mucosal microbiota of patients with active Crohn's disease (CD; n=42) and ulcerative colitis (UC; n=31) was compared with that of controls (n=33). TM7 consortia were examined using molecular techniques based on 16S rRNA genes, including clone libraries, sequencing and in situ hybridization. TM7 molecular signatures could be cloned from mucosal samples of both IBD patients and controls, but the composition of the clone libraries differed significantly. Taxonomic analysis of the sequences revealed a higher diversity of TM7 phylotypes in CD (23 different phylotypes) than in UC (10) and non-IBD controls (12). All clone libraries showed a high number of novel sequences (21 for controls, 34 for CD and 29 for UC). A highly atypical base substitution for bacterial 16S rRNA genes associated with antibiotic resistance was detected in almost all sequences from CD (97.3 %) and UC (100 %) patients compared to only 65.1 % in the controls. TM7 bacteria might play an important role in IBD similar to that previously described in oral inflammation. The alterations of TM7 bacteria and the genetically determined antibiotic resistance of TM7 species in IBD could be a relevant part of a more general alteration of bacterial microbiota in IBD as recently found, e.g. as a promoter of inflammation at early stages of disease.

Myeloid-Derived Suppressor Cells in Inflammatory Bowel Disease: A New Immunoregulatory Pathway

CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs) have been shown to cause T-cell tolerance in tumor-bearing mice; however, little is known about the role of MDSCs in chronic inflammation. Here, for the first time, we have identified and analyzed their role in inflammatory bowel disease (IBD). Repetitive adoptive transfer of clone 4/T-cell receptor (CL4-TCR) transgenic CD8(+) T cells into VILLIN-hemagglutinin (HA) transgenic mice was performed on days 1, 12, and 27. Recipient mice were analyzed for immunopathology, HA-specific CD8(+) T-cell responses, and CD11b(+)Gr-1(+) MDSCs (frequency, phenotype, expression analysis, and in vitro as well as in vivo function). In addition, peripheral blood from patients with active Crohn's disease and ulcerative colitis was examined for the presence and function of human MDSCs denoted as CD14(+)HLA-DR(-/low) cells. Repetitive transfer of HA-specific CD8(+) T cells prevented VILLIN-HA recipient mice from development of severe enterocolitis, which is seen after a single transfer of T cells. Repeated transfer of antigen-specific T cells led to an increase in the frequency of nitric oxide synthase 2 and arginase-expressing CD11b(+)Gr-1(+) MDSCs in spleen and intestine of VILLIN-HA mice with immunosuppressive function. Cotransfer of MDSCs with HA-specific CD8(+) T cells into naive VILLIN-HA mice ameliorated enterocolitis, indicating a direct immune regulatory effect of MDSCs on induction of IBD by antigen-specific T cells. Finally, an increase in the frequency of human MDSCs with suppressor function was observed in peripheral blood from patients with IBD. These results identify MDSCs as a new immune regulatory pathway in IBD.

Increased expression of VEGF and CD146 in patients with inflammatory bowel disease

Background . Angiogenesis has been suggested as an integral part of inflammatory bowel disease pathology. Vascular endothelial growth factor has long been considered to play a central, specific role in angiogenesis. Endothelial junction adhesion molecules, such as CD146, have recently been suggested to play a potent role in angiogenesis. CD34 is expressed on vascular endothelium, and it has been reported to be upregulated on endothelium in IBD. We investigated the expression of tissue vascular endothelial growth factor, CD34 and CD146 in the inflamed mucosa of patients with active inflammatory bowel disease compared with no inflamed mucosa of healthy controls. Methods. Forty-two IBD patients [23 ulcerative colitis, 19 Crohn's disease] and ten healthy controls were included in the study. In colonoscopically obtained biopsies, CD34, CD146 and vascular endothelial growth factor expression were evaluated by immunohistochemistry. Results. Vascular endothelial growth factor was detected in the mucosa of all groups, and its expression was significantly higher in both Crohn's disease and ulcerative colitis compared with controls ( p < 0.05). Immunohistochemical staining for CD146 in the inflamed mucosa was significantly higher in both Crohn's disease and ulcerative colitis compared with controls ( p = 0.002). A trend of higher CD34 expression in Crohn's disease and ulcerative colitis compared with controls was also found, but the difference among the three groups was not statistically significant ( p = 0.09). Conclusions . Inflamed mucosa of patients with active Crohn's disease and ulcerative colitis showed a markedly enhanced expression of VEGF and CD146, than normal mucosa of controls, indicating a possible role of angiogenesis in the pathogenesis of inflammatory bowel disease.

Un nouveau marqueur sérique de la pathologie inflammatoire de l’intestin : la protéine S100A12

S100A12 is a calcium binding protein with pro-inflammatory properties. It is secreted by activated neutrophils and interacts with the multiligand receptor for advanced glycation end products (RAGE), found on macrophages, endothelium and lymphocytes. It is strongly expressed in inflamed intestinal tissues of patients with active Crohn's disease and ulcerative colitis and circulating levels of S100A12 seem to be reliable markers of inflammation in monitoring disease activity. An Elisa-kit is under process by Cisbio international to measure concentrations of S100A12 in serum.

Nicotine Enemas for Active Crohn's Colitis: An Open Pilot Study

Background. Smoking has a detrimental effect in Crohn's disease (CD), but this may be due to factors in smoking other than nicotine. Given that transdermal nicotine benefits ulcerative colitis (UC), and there is a considerable overlap in the treatment of UC and CD, the possible beneficial effect of nicotine has been examined in patients with Crohn's colitis. Aims. To assess the efficacy and safety of nicotine enemas in active Crohn's colitis. Patients. Thirteen patients with active rectosigmoid CD; 3 patients were excluded because they received antibiotics. Methods. Subjects were given 6 mg nicotine enemas, each day for 4 weeks, in an open pilot study. At the beginning and end of the trial, a Crohn's disease activity index (CDAI) score was calculated, sigmoidoscopy was performed, and haematological inflammatory markers measured. Results. Mean CDAI decreased from 202 to 153—the score was reduced in 6 patients, unchanged in 3, and increased in one. Frequency of bowel movements decreased in 8 patients and the sigmoidoscopy grade was reduced in 7. Mean C-reactive protein decreased from 22.0 to 12.3 mg/L. There were no withdrawals due to adverse events. Conclusions. In this relatively small study of patients with active Crohn's colitis, 6 mg nicotine enemas appeared to be of clinical benefit in most patients. They were well tolerated and safe.

Interleukin-10 Blocked Endoplasmic Reticulum Stress in Intestinal Epithelial Cells: Impact on Chronic Inflammation

The initiation of endoplasmic reticulum (ER)-mediated stress responses in intestinal epithelial cells (IEC) may contribute to the pathogenesis of chronic intestinal inflammation. The aim of the study was to use functional epithelial cell proteomics to characterize anti-inflammatory mechanisms of interleukin 10 (IL-10). Primary IEC were isolated from Enterococcus faecalis-monoassociated IL-10-deficient (IL-10-/-) and wild-type mice to perform 2D-gel sodium-dodecyl-sulfate polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. In addition, IEC from 6 patients with active Crohn's disease, ulcerative colitis, and sigmoid diverticulitis as well as noninflamed controls were purified. Molecular protective mechanisms of IL-10 were characterized in tumor necrosis factor (TNF)-stimulated IL-10 receptor (IL-10R) reconstituted epithelial cells. Primary IEC from IL-10-/- mice as well as inflammatory bowel disease patients revealed increased expression levels of the glucose-regulated ER stress protein (grp)-78 under conditions of chronic inflammation. Consistent with the observation that TNF induced ER stress responses through grp-78 redistribution from the ER lumen to the cytoplasmic IkappaB kinase complex, grp-78 knockdown completely abolished TNF-induced nuclear factor-kappaB RelA phosphorylation in epithelial cell cultures. Interestingly, IL-10 inhibited grp-78 protein and messenger RNA expression in IL-10R reconstituted IEC. Chromatin immunoprecipitation analysis and immunofluorescence microscopy revealed that IL-10-mediated p38 signaling inhibited TNF-induced recruitment of the ER-derived activating transcription factor (ATF)-6 to the grp-78 promoter likely through the blockade of ATF-6 nuclear translocation. Primary IEC from inflamed IL-10-/- mice and inflammatory bowel disease patients revealed activated ER stress responses in the intestinal epithelium. IL-10 inhibits inflammation-induced ER stress response mechanisms by modulating ATF-6 nuclear recruitment to the grp-78 gene promoter.

Crohnʼs Disease Manifested as Rhinitis

This vignette relates an extremely rare manifestation of Crohn's disease and underscores the neccesity of considering Crohn's disease as the underlying cause of symptoms of obscure etiology. Past medical history was obtained, and physical examination and biopsies were performed ona patient with complaints of rhinitis. A 54 year old female with a history of active Crohn's colitis presented to her otolaryngologist with a complaint of rhinitis. She had persistent upper respiratory symptoms of cough and nasal congestion for several months that did not respond to various non-prescription medications. She also noted pain and irritation, localized to the inside of the right nostril, increasing in intensity over the last two to three weeks with small amounts of clear nasal discharge. Physical examination revealed a well appearing female in no distress. She was normotensive and afebrile. She was noted only to have bilateral high septal deflections. No facial tenderness or purulent discharge was noted. Her serum chemistries and complete blood count were within normal limits. Nasal endoscopy was normal. Biopsy, however, showed edema, giant cells and multiple noncaseating granulomas in the right nasal passage. Extraintestinal manifestations of Crohn's disease of the gastrointestinal tract are a well recognized phenomena. Biopsy typically shows edema of the lamina propria, perivascular inflammation with infiltrates and noncaseating granulomas with multinucleated Langerhans type giant cells. The differential diagnosis in this case included Wegener's granulomatosis and Crohn's disease. Nasal involvement is extremely rare. To date, only five cases of nasal Crohn's disease have been reported and is typified by chronic mucosal inflammation, obstruction, bleeding and occasionally septal perforation. All prior five patients were treated with oral steroids and or systemic corticosteroids with good results. Nasal involvement in Crohn's disease is extremely rare. Its findings after benign physical and endoscopic examination of the nasal passages suggest that this may be an underreported phenomenon.

TNFα production to TLR2 ligands in active IBD patients

Strong evidence suggests that microbial components are involved in the etiopathology of inflammatory bowel diseases (IBD). Since pathogen-associated molecular patterns are recognized by TLRs, dysregulation of TLR-mediated microbial recognition could be taking place in IBD patients. An in vitro assay with different TLR agonists was used to reproduce the immunostimulation via TLR ligands. Elevated TNFα production was found in response to LTA and Zymosan in 48% of active Crohn's disease and ulcerative colitis patients when compared to inactive patients or controls. The expression of CD14 did not differ in active patients, whereas TLR2 was significantly upregulated on monocytes from 71% of those patients with high production of TNFα. The marked increase of TNFα response to TLR2 ligands correlated with a higher TLR2 expression in a group of IBD patients, suggesting that an abnormal mechanism may provide an excess of inflammatory mediators during the active phase of IBDs.