Ulcerative Colitis: Sturm A

Sturm A, de Souza HS, Fiocchi C. · Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Campus Virchow Clinic, Augustenburger Platz 1, 13353 Berlin, Germany. · Curr Drug Targets. · Pubmed #18473766 No free full text.

Abstract: Both forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), represent prototypical conditions whose most salient features are the presence of chronic inflammation involving various parts of the intestinal tract and an increased risk of cancer, which is a complication directly related to the duration and activity of gut inflammation. Several factors have been implicated in the unrelenting mucosal inflammation of IBD, prominent among them being the presence of a persistently elevated number of activated T cells in the mucosa of CD and UC patients. These T cells display various defects of proliferation and apoptosis, and these abnormalities are credited with directly contributing to the pathogenesis of IBD and possibly the progression to colon cancer. This notion is supported by the observation that T cells are also prominently found infiltrating most tumors and are functionally impaired compared to T cells in the circulation. This establishes a parallel that may constitute a link between chronic intestinal inflammation and the development of malignancies in the inflamed intestine. This article will review some of the basic features of human intestinal mucosal T cells, examine the mechanisms underlying the processes of cell cycling and cell death, describe the defective proliferative and apoptotic function detected in CD and UC, and discuss the implications of modulating T cell apoptosis in IBD for therapeutic purposes and eventually decreasing the risk of cancer development.

Dignass AU, Baumgart DC, Sturm A. · Department of Medicine, Division of Hepatology and Gastroenterology, Charité Medical School--Virchow Hospital, Berlin, Germany. · Aliment Pharmacol Ther. · Pubmed #15352888 links to  free full text

Abstract: Although the aetiopathogenesis of Crohn's disease and ulcerative colitis, remains unsolved, current evidence indicates that defective T-cell apoptosis and impairment of intestinal epithelial barrier function play important roles in the pathogenesis of both conditions. Without appropriate control of T-cell proliferation and death during an immune response, an inappropriate accumulation of T cells and subsequent intestinal inflammation may occur. Differences in T-cell responses between Crohn's disease and ulcerative colitis have been identified, with mucosal T-cell apoptosis being defective in Crohn's disease, but not in ulcerative colitis. Furthermore, cell cycling is considerably faster, with a vigorous clonal expansion, in Crohn's disease, whereas, in ulcerative colitis, T cells cycle normally, but have a remarkably reduced capacity to divide and expand. The elimination of excessive T cells therefore seems to be a reasonable approach to restore the gut to a physiological state or, at least, a controlled state of inflammation. The tumour necrosis factor-alpha blocker, infliximab, exerts its beneficial effects, at least in part, by the induction of apoptosis in lamina propria T cells and monocytes. In addition, repeated damage and injury of the intestinal surface is a hallmark of inflammatory bowel disease and may facilitate the entry of luminal antigens into the mammalian organism and the initiation and perpetuation of both nonspecific and specific immune responses. A better understanding of and enhancement of intestinal repair mechanisms may thus provide future approaches for the treatment of inflammatory bowel disease.

Vetrano S, Rescigno M, Cera MR, Correale C, Rumio C, Doni A, Fantini M, Sturm A, Borroni E, Repici A, Locati M, Malesci A, Dejana E, Danese S. · Division of Gastroenterology, Istituto di Ricerca e Cura a Carattere Scientifico Istituto Clinico Humanitas, University of Milan, Rozzano, Italy. · Gastroenterology. · Pubmed #18514073 No free full text.

Abstract: BACKGROUND & AIMS: Junctional adhesion molecule-A (JAM-A) is localized at the tight junctions and controls leukocyte migration into the tissues. However, its functional role in inflammatory bowel disease (IBD) is unexplored. METHODS: Control, Crohn's disease (CD), and ulcerative colitis (UC) tissue specimens were studied for JAM-A expression, as well as the colon of mice given dextran sodium sulfate (DSS). Wild-type and JAM-A(-/-), Tie-2-Cre-JAM-A(-/-) (endothelial/hematopoietic-specific JAM inactivation) mice were studied for susceptibility to DSS. Disease activity and colonic inflammation were assessed using a disease activity index histology and endoscopy, and mucosal cytokines were measured by enzyme-linked immunosorbent assay. JAM-A function was investigated by RNA silencing in epithelial cells, and apoptosis was measured. RESULTS: In both CD and UC, as well as in experimental colitis, there is a loss of epithelial but not endothelial JAM-A expression. Deletion of JAM-A results in a dramatic increase in susceptibility to DSS colitis, as assessed by weight loss, disease activity index, histologic and endoscopic severity, and strikingly high mortality rates. This is not caused by the absence of JAM-A in the endothelial or hematopoietic compartments because Tie-2-Cre-JAM-A(-/-) mice are no more susceptible to DSS colitis than wild-type animals. JAM-A(-/-) mice displayed increased intestinal permeability and inflammatory cytokine production, and marked epithelial apoptosis. Silencing of JAM-A in intestinal epithelial cells resulted in increased permeability in vitro. CONCLUSIONS: Our results show a nonredundant and novel role of JAM-A in controlling mucosal homeostasis by regulating the integrity and permeability of epithelial barrier function.

Berndt U, Philipsen L, Bartsch S, Wiedenmann B, Baumgart DC, Hämmerle M, Sturm A. · Department of Medicine, Division of Gastroenterology and Hepatology, Charité-Campus Virchow Klinikum, Universitätsmedizin Berlin, Berlin, Germany. · Cancer Res. · Pubmed #18245490 links to  free full text

Abstract: The immune system is a significant determinant of epithelial tumorigenesis, but its role in colorectal cancer pathogenesis is not well understood. The function of the immune system depends upon the integrity of the protein network environment, and thus, we performed MELC immunofluorescence microscopy focusing on the lamina propria. By analyzing structurally intact tissues from colorectal cancer, ulcerative colitis, and healthy colonic mucosa, we used this unique and novel highly multiplexed robotic-imaging technology, which allows visualizing dozens of proteins simultaneously, and explored the toponome in colorectal cancer mucosa for the first time. We identified 1,930 motifs that distinguish control from colorectal cancer tissue. In colorectal cancer, the number of activated T cells is increased, explained by a lack of bax, caspase-3, and caspase-8. Whereas CD4(+)CD25(+) T cells are decreased and are, other than in ulcerative colitis, not activated, cytotoxic T cells are significantly increased in colorectal cancer. Furthermore, the number of activated human lymphocyte antigen (HLA)-DR(+) T-cells is increased in colorectal cancer, pointing to an altered antigen presentation. In colorectal cancer, CD3(+)CD29(+) expression and assembly of the LFA-1 and LFA-3 receptor are differentially changed, indicating a distinct regulation of T-cell adhesion in colorectal cancer. We also identified increased numbers of natural killer and CD44(+) cells in the colorectal cancer mucosa and nuclear factor-kappaB as regulator of apoptosis in these cell populations. High-content proteomic analysis showed that colorectal cancer induces a tremendous modification of protein expression profiles in the lamina propria. Thus, topological proteomic analysis may help to unravel the role of the adaptive immune system in colorectal cancer and aid the development of new antitumor immunotherapy approaches.

Büning C, Schmidt HH, Molnár T, Drenth JP, Fiedler T, Gentz E, Todorov T, Baumgart DC, Sturm A, Nagy F, Lonovics J, de Jong DJ, Landt O, Kage A, Nickel R, Büttner J, Lochs H, Witt H. · Department of Gastroenterology, Hepatology & Endocrinology, Charité, Campus Mitte, Universitätsmedizin Berlin, Germany. · Inflamm Bowel Dis. · Pubmed #18092344 links to  free full text

Abstract: BACKGROUND: A recent study reported that the c.30T>A (p.Cys10Ter; rs2043211) variant, in the CARD8 (TUCAN) gene, is associated with Crohn's disease (CD). The aim of this study was to analyze the frequency of p.C10X in 3 independent European (IBD) cohorts from Germany, Hungary, and the Netherlands. METHODS: We included a European IBD cohort of 921 patients and compared the p.C10X genotype frequency to 832 healthy controls. The 3 study populations analyzed were: (1) Germany [CD, n = 317; ulcerative colitis (UC), n = 180], (2) Hungary (CD, n = 149; UC, n = 119), and (3) the Netherlands (CD, n = 156). Subtyping analysis was performed in respect to NOD2 variants (p.Arg702Trp, p.Gly908Arg, c.3020insC) and to clinical characteristics. Ethnically matched controls were included (German, n = 413; Hungarian, n = 202; Dutch, n = 217). RESULTS: We observed no significant difference in p.C10X genotype frequency in either patients with CD or patients with UC compared with controls in all 3 cohorts. Conversely to the initial association study, we found a trend toward lower frequencies of the suggestive risk wild type in CD from the Netherlands compared with controls (P = 0.14). We found neither evidence for genetic interactions between p.C10X and NOD2 nor the C10X variant to be associated with a CD or UC phenotype. CONCLUSIONS: Analyzing 3 independent European IBD cohorts, we found no evidence that the C10X variant in CARD8 confers susceptibility for CD.

Büning C, Schmidt HH, Molnar T, De Jong DJ, Fiedler T, Bühner S, Sturm A, Baumgart DC, Nagy F, Lonovics J, Drenth JP, Landt O, Nickel R, Büttner J, Lochs H, Witt H. · Department of Gastroenterology, Hepatology and Endocrinology, Charité, Campus Mitte, Universitätsmedizin Berlin, Berlin, Germany. · Aliment Pharmacol Ther. · Pubmed #17877509 No free full text.

Abstract: BACKGROUND: A recent study reported that a non-synonymous single nucleotide polymorphism (rs11209026, p.Arg381Gln) located in the IL23R gene is a protective marker for inflammatory bowel disease. AIM: To analyse the frequency of p.Arg381Gln in three independent European inflammatory bowel disease cohorts and to evaluate how this variant influences disease behaviour. METHODS: We assessed a European cohort of 919 inflammatory bowel disease patients and compared the IL23R p.Arg381Gln genotype frequency with 845 healthy controls. Inflammatory bowel disease patients originated from Germany [Crohn's disease (CD): n = 318; ulcerative colitis (UC): n = 178], Hungary (CD: n = 148; UC: n = 118) and the Netherlands (CD: n = 157). Ethnically matched controls were included. We performed subtyping analysis in respect to CARD15 alterations and clinical characteristics. RESULTS: The frequency of the glutamine allele of p.Arg381Gln was significantly lower in inflammatory bowel disease patients compared with controls in a pooled analysis of all three cohorts (P < 0.000001) as well as in the individual cohorts (Germany: P = 0.001, Hungary: P = 0.02 and the Netherlands: P = 0.0002). The p.Arg381Gln genotype distribution was similar between CD and UC. We did not observe either statistical interactions between p.Arg381Gln and CARD15 variants or any significant associations between p.Arg381Gln genotype and subphenotypes. CONCLUSIONS: The p.Arg381Gln IL23R variant confers a protective effect against both CD and UC, but does not determine disease phenotype.

Berndt U, Bartsch S, Philipsen L, Danese S, Wiedenmann B, Dignass AU, Hämmerle M, Sturm A. · Division of Gastroenterology and Hepatology, Department of Medicine, Charité-Campus Virchow Clinic, Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany. · J Immunol. · Pubmed #17579049 links to  free full text

Abstract: Although Crohn's disease (CrD) and ulcerative colitis (UC) share several clinical features, the mechanisms of tissue injury differ. Because the global cellular function depends upon the protein network environment as a whole, we explored changes in the distribution and association of mucosal proteins to define key events involved in disease pathogenesis. Endoscopic biopsies were taken from CrD, UC, and control colonic mucosa, and Multi-Epitope-Ligand-Cartographie immunofluorescence microscopy with 32 different Abs was performed. Multi-Epitope-Ligand-Cartographie is a novel, highly multiplexed robotic imaging technology which allows integrating cell biology and biomathematical tools to visualize dozens of proteins simultaneously in a structurally intact cell or tissue. In CrD, the number of CD3+CD45RA+ naive T cells was markedly increased, but only activated memory, but not naive, T cells expressed decreased levels of Bax, active caspase-3 or -8. In UC, only CD4+ T cells coexpressing NF-kappaB were caspase-8 and poly(ADP-ribose)-polymerase positive. Furthermore, the number of CD4+CD25+ T cells was elevated only in UC, whereas in CrD and controls, the number of these cells was similar. By using hub analysis, we also identified that the colocalization pattern with NF-kappaB+ and poly(ADP-ribose)-polymerase+ as base motifs distinguished CrD from UC. High-content proteomic analysis of the intestinal mucosa demonstrated for the first time that different T cell populations within the intestinal mucosa express proteins translating distinct biological functions in each form of inflammatory bowel disease. Thus, topological proteomic analysis may help to unravel the pathogenesis of inflammatory bowel disease by defining distinct immunopathogenic profiles in CrD and UC.

Holtmann MH, Krummenauer F, Claas C, Kremeyer K, Lorenz D, Rainer O, Vogel I, Böcker U, Böhm S, Büning C, Duchmann R, Gerken G, Herfarth H, Lügering N, Kruis W, Reinshagen M, Schmidt J, Stallmach A, Stein J, Sturm A, Galle PR, Hommes DW, D'Haens G, Rutgeerts P, Neurath MF. · First Department of Medicine, Johannes Gutenberg University, Mainz, Germany. · Dig Dis Sci. · Pubmed #16927148 No free full text.

Abstract: In Crohn's disease the optimal duration of azathioprine treatment is still controversial and for ulcerative colitis only limited data are available to support its efficacy. Charts of 1176 patients with IBD from 16 European centers were analyzed. Flare incidences and steroid dosages were assessed for the time before and during treatment and after discontinuation. Within the first 4 years, azathioprine suppressed flare incidence and steroid consumption in both diseases (P < 0.001). While in CD discontinuation after 3-4 years did not lead to reactivation, this was the case in UC. However, continuation beyond 4 years further improved clinical activity in CD and steroid requirement in both diseases (P < 0.001). Discontinuation of azathioprine may thus be considered after 3-4 years in CD patients in complete remission without steroid requirement. In all other CD patients and for UC patients in general, continuation seems beneficial. These results support a novel differential algorithm for long-term azathioprine therapy in IBD.

Grabig A, Paclik D, Guzy C, Dankof A, Baumgart DC, Erckenbrecht J, Raupach B, Sonnenborn U, Eckert J, Schumann RR, Wiedenmann B, Dignass AU, Sturm A. · Charité-Universitätsmedizin Berlin, Campus Virchow Clinic, Department of Hepatology and Gastroenterology, Augustenburger Platz 1, D-13353 Berlin, Germany. · Infect Immun. · Pubmed #16790781 links to  free full text

Abstract: Toll-like receptors (TLRs) are key components of the innate immune system that trigger antimicrobial host defense responses. The aim of the present study was to analyze the effects of probiotic Escherichia coli Nissle strain 1917 in experimental colitis induced in TLR-2 and TLR-4 knockout mice. Colitis was induced in wild-type (wt), TLR-2 knockout, and TLR-4 knockout mice via administration of 5% dextran sodium sulfate (DSS). Mice were treated with either 0.9% NaCl or 10(7) E. coli Nissle 1917 twice daily, followed by the determination of disease activity, mucosal damage, and cytokine secretion. wt and TLR-2 knockout mice exposed to DSS developed acute colitis, whereas TLR-4 knockout mice developed significantly less inflammation. In wt mice, but not TLR-2 or TLR-4 knockout mice, E. coli Nissle 1917 ameliorated colitis and decreased proinflammatory cytokine secretion. In TLR-2 knockout mice a selective reduction of gamma interferon secretion was observed after E. coli Nissle 1917 treatment. In TLR-4 knockout mice, cytokine secretion was almost undetectable and not modulated by E. coli Nissle 1917, indicating that TLR-4 knockout mice do not develop colitis similar to the wt mice. Coculture of E. coli Nissle 1917 and human T cells increased TLR-2 and TLR-4 protein expression in T cells and increased NF-kappaB activity via TLR-2 and TLR-4. In conclusion, our data provide evidence that E. coli Nissle 1917 ameliorates experimental induced colitis in mice via TLR-2- and TLR-4-dependent pathways.

Baumgart DC, Pintoffl JP, Sturm A, Wiedenmann B, Dignass AU. · Department of Medicine, Division of Hepatology and Gastroenterology, Charité Medical Center, Virchow Hospital, Medical School of the Humboldt-University of Berlin, Germany. · Am J Gastroenterol. · Pubmed #16573777 No free full text.

Abstract: OBJECTIVE: We and others have reported the use of tacrolimus in refractory inflammatory bowel disease (IBD). Little is known about its long-term efficacy and safety. METHODS: In this retrospective, observational single center study the charts of 53 adult patients with steroid-dependent (n = 18) or steroid-refractory (n = 35) IBD, Crohn's disease (CD) (n = 11), ulcerative colitis (UC) (n = 40), or pouchitis (PC) (n = 2) were reviewed. Tacrolimus (0.1 mg/kg body weight per day) was administered orally in all and initially intravenously in 2 patients (0.01 mg/kg body weight per day), aiming for serum trough levels of 4-8 ng/mL. Forty-one of 53 (77.1%) patients were receiving concomitant azathioprine. The mean treatment duration was 25.2 +/- 4.6 SD months (0.43-164 months). Patients were followed for a mean of 39 +/- 4.1 SD months (5-164 months). Response was evaluated using a modified clinical activity index (M-CAI). RESULTS: Thirty-one UC (78%), 10 CD (90.1%), and both PC (100%) patients experienced an immediate clinical response or went into remission at 30 days. A statistically significant drop on the M-CAI was documented for UC and CD patients. Nine UC patients (22.5%) underwent colectomy between 1.6 and 41.3 months following initiation. Mean colectomy-free survival was 104.8 +/- 15.5 (95% CI 74.4-135.2) months (limited to 164.4 months). Cumulative colectomy-free survival was estimated 56.5% at 43.8 months. Steroids were reduced or discontinued in 40 of 45 UC and CD patients (90%) taking steroids. Side effects included a temporary rise of creatinine (n = 4, 7.6%), tremor or paresthesias (n = 5, 9.4%), hyperkalemia (n = 1, 1.9%), hypertension (n = 1, 1.9%), and opportunistic infections (n = 2, 3.8%). CONCLUSION: Long-term tacrolimus therapy appears safe and effective in refractory IBD.

Musso A, Dentelli P, Carlino A, Chiusa L, Repici A, Sturm A, Fiocchi C, Rizzetto M, Pegoraro L, Sategna-Guidetti C, Brizzi MF. · Division of Gastroenterology, Ospedale San Giovanni Battista, University of Torino, Torino, Italy. · Inflamm Bowel Dis. · Pubmed #15677901 No free full text.

Abstract: Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of chronic inflammatory bowel disease (IBD), are characterized by mucosal immune cell activation that is driven by a cytokine imbalance. Several cytokines involved in IBD act through the activation of the signal transducers and activators of transcription (STAT) family. We investigated the activation of STAT3 in the mucosa of CD and UC patients, and evaluated whether this event is specific for IBD patients. Using immunofluorescence and immunoblotting, total and phosphorylated STAT3 levels were assessed in biopsy specimens, isolated lamina propria mononuclear cells, and peripheral blood mononuclear cells from patients with CD, UC, other forms of intestinal inflammation, and control subjects. Immunoblotting revealed phosphorylated STAT3 in mucosal biopsy specimens from patients with CD, UC, celiac disease, and acute self-limited colitis, but not in the normal mucosa of control subjects. In IBD patients, STAT3 activation was confined to actively inflamed areas. Accordingly, activated STAT3 was detected in isolated lamina propria mononuclear cells from inflamed IBD tissues, but not in peripheral blood mononuclear cells from control subjects or IBD patients. Immunofluorescence demonstrated that the sources of activated STAT3 were macrophages and T lymphocytes, but not neutrophils. STAT3 activation also was detected in T cells infiltrating the duodenal mucosa of celiac disease patients. We conclude that STAT3 signaling occurs in both CD and UC, where it is strictly confined to areas of active inflammation and is limited to infiltrating macrophages and T cells. The occurrence of STAT3 signaling in other acute and chronic intestinal inflammatory conditions suggests that, rather than a specific feature of IBD, it represents a fundamental signaling pathway that is shared by multiple forms of gut inflammation.

Baumgart DC, Metzke D, Schmitz J, Scheffold A, Sturm A, Wiedenmann B, Dignass AU. · Charité Medical Centre-Virchow Hospital, Medical School of the Humboldt-University, Department of Medicine, Division of Hepatology & Gastroenterology, D-13344 Berlin, Germany. · Gut. · Pubmed #15647187 links to  free full text

Abstract: BACKGROUND: Breakdown of tolerance against the commensal microflora is believed to be a major factor in the pathogenesis of inflammatory bowel disease (IBD). Dendritic cells (DC) have been implicated in this process in various animal models, but data on human DC in IBD are very limited. AIM: To characterise plasmacytoid DC (PDC) and myeloid DC (MDC) in patients with active versus inactive IBD and healthy controls. PATIENTS AND METHODS: Peripheral blood was obtained from 106 patients (Crohn's disease (CD) n=49, ulcerative colitis (UC) n=57) and healthy controls (n=19). Disease activity was scored using the modified Truelove Witts (MTWSI) for UC and the Harvey Bradshaw severity indices (HBSI) for CD. Four colour flow cytometric analysis was used to identify, enumerate, and phenotype DC. DC from patients with acute flare ups and healthy controls were cultured and stimulated with CpG ODN 2006 or lipopolysaccharide (LPS). RESULTS: IBD patients in remission (PDC UC, 0.39%; CD, 0.35%; MDC-1 UC, 0.23%; CD, 0.22% of PBMC) have slightly lower numbers of circulating DC compared with healthy controls (PDC 0.41%, MDC-1 0.25% of PBMC). In acute flare ups IBD patients experience a significant drop of DC (PDC UC, 0.04%; CD, 0.11%; MDC-1 UC, 0.11%; CD, 0.14% of PBMC) that correlates with disease activity (correlation coefficients: PDC MTWSI, 0.93; HBSI, 0.79; MDC-1 MTWSI, 0.75; HBSI, 0.81). Moreover, both express alpha4beta7 integrin and display an immature phenotype. Freshly isolated PDC and MDC-1 from untreated flaring IBD patients express higher baseline levels of CD86 which increases further in culture and upon stimulation compared with healthy controls. CONCLUSION: IBD patients lack immature blood DC during flare ups which possibly migrate to the gut. An aberrant response to microbial surrogate stimuli suggests a disturbed interaction with commensals.

Sturm A, Leite AZ, Danese S, Krivacic KA, West GA, Mohr S, Jacobberger JW, Fiocchi C. · Department of Medicine, University Hospitals of Cleveland, Case Western Reserve University School of Medicine (BRB 425), 10900 Euclid Ave, Cleveland, Ohio, 44106-4952, USA. · Gut. · Pubmed #15479683 links to  free full text

Abstract: BACKGROUND: Different abnormalities of T cell effector function distinguish Crohn's disease (CD) from ulcerative colitis (UC). Because cell cycling determines effector function, pathogenic events in CD and UC may depend on cell cycle changes unique to each condition. METHODS: Cell cycle kinetics, cycle regulatory molecule expression, apoptosis, caspase and telomerase activity, and cellular expansion were evaluated in CD2 and CD3 activated control, CD, and UC lamina propria T cells. RESULTS: Compared with normal cells, CD T cells cycle faster, express increased phosphorylated Rb and decreased phosphorylated p53 levels, display less caspase activity but more telomerase activity, die less, and undergo vigorous cellular expansion. In contrast, UC T cells cycle slower, express normal levels of phosphorylated Rb and p53, display more caspase activity but have no telomerase activity, die more, and have a limited capacity to expand. CONCLUSIONS: T cell cycle abnormalities in CD indicate a state of hyperreactivity compatible with loss of tolerance, but a hyporeactive state compatible with anergy in UC. Thus distinct and divergent T cell cycle characteristics underlie the pathogenesis of the two main forms of inflammatory bowel disease.

Sturm A, Schulte C, Schatton R, Becker A, Cario E, Goebell H, Dignass AU. · Division of Gastroenterology and Hepatology, University of Essen, Germany. · Eur J Gastroenterol Hepatol. · Pubmed #10783999 No free full text.

Abstract: OBJECTIVE: An increased mucosal expression of transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF) has been reported in patients with active inflammatory bowel diseases (IBD) and in proximity to injured gastric and intestinal mucosal surfaces. The aim of this study was to measure systemic concentrations of TGF-beta and HGF and to assess their potential value to predict disease activity or severity of inflammation in patients with inflammatory bowel diseases. DESIGN AND METHODS: Plasma HGF and TGF-beta1 peptide levels were determined in 29 patients with ulcerative colitis, 45 patients with Crohn's disease and 28 healthy controls using commercial ELISA assays. Peptide levels were correlated with disease activity indices and various laboratory parameters. RESULTS: HGF and TGF-beta1 plasma levels were detected in all control and IBD subjects. Although a tendency towards increased HGF and TGF-beta1 peptide levels in IBD patients was observed, differences between groups were not significant In ulcerative colitis patients HGF plasma levels positively correlated with white blood cell counts and negatively correlated with serum albumin concentrations and haematocrit. In Crohn's disease patients, a positive correlation between TGF-beta and platelet count was observed. CONCLUSIONS: HGF and TGF-beta1 plasma concentrations are not significantly different in IBD and healthy control subjects. Stratification of IBD patients according to disease activity did not reveal any substantial differences, suggesting that HGF and TGF-beta plasma levels have no value in the assessment of disease activity or severity of inflammation in patients with IBD.

Baumgart DC, Sturm A, Wiedenmann B, Dignass AU. · No affiliation provided · Gut. · Pubmed #16120758 links to  free full text

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