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Herbert Tilg

Publications and source records attributed to Herbert Tilg.

At least 37 records · Page 2Linked to original sources
PubMed2005

H. pylori infection increases levels of exhaled nitrate.

BACKGROUND: Helicobacter pylori infection is one of the most common chronic bacterial infections worldwide. Despite the existence of a breath test for the diagnosis of H. pylori infection, no study has described the composition of volatile compounds, especially the levels of nitrate, in the exhaled air of patients with H. pylori infection. MATERIALS AND METHODS: The volatile compounds in the exhaled air of 14 patients suffering from H. pylori gastritis and 11 controls were analyzed using proton transfer reaction-mass spectrometry. Gastric biopsy was used to establish diagnosis of current H. pylori infection. RESULTS: Comparing mass spectra between groups, Mass 28 (hydrogen cyanide, HCN) and Mass 64 (hydrogen nitrate, H2NO3) were found to be significantly elevated in patients with H. pylori infection. CONCLUSIONS: The main result of the present study is that in H. pylori-infected patients, levels of exhaled hydrogen nitrate and hydrogen cyanide are found to be significantly elevated. However, further studies are necessary to find out whether the differences in the detected mass spectrum are specific enough to differentiate patients with H. pylori gastritis from healthy controls.

Adult↗
PubMed2005

Adiponectin: a key fat-derived molecule regulating inflammation.

Adiponectin is the abundant adipocyte-derived protein with well-established anti-atherogenic and insulin-sensitising properties. Besides these well characterised biological functions, recent evidence supports a strong anti-inflammatory function. Whereas initial studies demonstrated that adiponectin suppresses the production of the potent pro-inflammatory cytokine TNF-alpha, current studies showed that this adipokine also induces various anti-inflammatory cytokines, such as IL-10 or -1 receptor antagonists. These effects are paralleled by various other immune-regulatory properties, such as specific effects on endothelial cell functions. These in vitro effects are directly translated into various animal models of inflammation, demonstrating a potent anti-inflammatory effect for adiponectin. Thiazolidinediones selectively upregulate peroxisome-proliferator-activated receptor-gamma, leading to increased tissue and serum concentrations of adiponectin. Adiponectin has emerged as a key mediator regulating and affecting the balance between fat and inflammation. Therefore, either adiponectin itself or its inducing agents, such as thiazolidinediones, might be of key therapeutic interest in the near future far beyond diseases being associated with insulin resistance.

Adipocytes↗
PubMed2004

Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes.

There is increasing evidence that the adipose tissue and immunologic processes are closely linked. The most abundant protein within the adipocyte is adiponectin. Our current work reports that adiponectin has potent immuno-suppressive properties, as it induces the production of the anti-inflammatory mediators IL-10 and IL-1RA in primary human monocytes, monocyte-derived macrophages, and dendritic cells. In addition, adiponectin significantly impaired the production of the pro-inflammatory cytokine IFN-gamma in human macrophages. Moreover, adiponectin-treated macrophages exhibit a reduced phagocytotic and allo-stimulatory capacity. However, we could not detect any functional deficits or phenotypic changes in adiponectin-treated monocytes and monocyte-derived DC. In summary, the presented data support the idea that adiponectin might be of critical relevance for cytokine regulation in obesity and fatty liver diseases affecting primarily macrophage functions. This might represent a fundamental link between over-nutrition and an impaired inflammatory immune response.

Adiponectin↗
PubMed2004

Overexpression of indoleamine 2,3-dioxygenase in human inflammatory bowel disease.

T-cells are causally involved in the pathogenesis of inflammatory bowel disease (IBD). The tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO) regulates T-cell proliferation and survival. We show in this report that IDO mRNA is markedly induced in lesional colonic biopsies of IBD patients. IDO is primarily expressed in CD123(+) mononuclear cells infiltrating the submucosal areas of the inflamed lesions. In Crohn's disease (CD), IDO is also strongly expressed in perifollicular regions of lymphoid follicles. Upregulation of IDO is of functional significance, as we detected an increase of kynurenine and of the kynurenine/tryptophan ratio in supernatants from colonic explant cultures (CECs) of CD patients. Immunohistochemistry of colonic biopsies taken from CD patients prior and after treatment with the TNF-blocking antibody Infliximab revealed reduced IDO expression in patients with good clinical response to Infliximab. In summary, high local expression of IDO may represent an anti-inflammatory mechanism tempting to counterbalance the tissue-damaging effects of activated T-cells infiltrating the colonic mucosa in IBD.

Adult↗
PubMed2004

Increased expression of CCL20 in human inflammatory bowel disease.

Inflammatory bowel disease (IBD) constituting Crohn's disease (CD) and ulcerative colitis (UC) is related to a dysregulated T cell response. CCL20 attracts memory T lymphocytes and dendritic cells. We asked whether CCL20 expression is altered in IBD. Colonic biopsies were obtained from 114 subjects with IBD, non-IBD colitis, irritable bowel syndrome, and healthy controls. CCL20 and CCR6 mRNA expression was measured by Taqman-PCR, and protein secretion from colonic explant cultures (CEC) and its regulation by TNF-alpha by ELISA. CCL20, CCR6, and Langerin were identified by immunohistochemistry and immunofluorescence. CCL20 mRNA and protein were severalfold increased in involved CD and UC but not in non-IBD colitis. TNF-alpha increased and anti-TNF-alpha decreased CCL20 release in healthy control CEC but not in involved IBD colonic specimens. CCL20 localized to follicle-associated epithelium, and CCR6 to the adjacent mantle zone of lymphoid follicles. Furthermore, abundant numbers of Langerin(+) immature dendritic cells were identified in the subepithelial space of IBD specimens. CCL20 might regulate the attraction of T lymphocytes and dendritic cells in IBD.

Adult↗
PubMed2004

Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice.

BACKGROUND & AIMS: Because the mechanisms leading to bile duct damage in sclerosing cholangitis are unknown, we aimed to determine the pathogenesis of bile duct injury in multidrug resistance gene (Mdr2) (Abcb4) knockout mice (Mdr2(-/-)) as a novel model of the disease. METHODS: Mdr2(-/-) and wild-type controls (Mdr2(+/+)) were studied at 2, 4, and 8 weeks of age. Liver histology, ultrastructure, immunofluorescence microscopy (to study inflammatory cells, tight junction protein ZO-1, basement membrane protein laminin, fluorescence-labeled ursodeoxycholic acid), immunohistochemistry (for alpha-smooth muscle actin, nitrotyrosine), sirius red staining, bacterial cultures of intra-abdominal organs, and polymerase chain reaction (PCR) for Helicobacter bilis DNA were compared between both genotypes. Hepatic cytokine expression was determined by reverse-transcription PCR. RESULTS: Bile ducts of Mdr2(-/-) showed disrupted tight junctions and basement membranes, bile acid leakage into portal tracts, induction of a portal inflammatory (CD11b, CD4-positive) infiltrate, and activation of proinflammatory (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta) and profibrogenic cytokines (transforming growth factor [TGF]-beta1). This resulted in activation of periductal myofibroblasts, leading to periductal fibrosis, separating the peribiliary plexus from bile duct epithelial cells and, finally, causing atrophy and death of the bile duct epithelium. Bacterial translocation was not increased and H. bilis was not detectable in Mdr2(-/-). CONCLUSIONS: Sclerosing cholangitis in Mdr2(-/-) mice is a multistep process with regurgitation of bile from leaky ducts into the portal tracts, leading to induction of periductal inflammation, followed by activation of periductal fibrogenesis, finally causing obliterative cholangitis owing to atrophy and death of bile duct epithelial cells.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2004

Austrian infliximab experience in Crohn's disease: a nationwide cooperative study with long-term follow-up.

OBJECTIVE: To determine the nationwide experience with infliximab for the treatment of Crohn's disease in Austria. DESIGN: National multicentre retrospective postal questionnaire survey. SETTING AND PARTICIPANTS: All institutions using infliximab for Crohn's disease in the years 1999 and 2000 were identified by the registry of the local provider of this drug. OUTCOME MEASURES: Response after first treatment course according to physician global assessment, number of subsequent infliximab infusions, disease activity at end of follow-up, avoidance of steroids, frequency of surgery for Crohn's disease, and adverse events. RESULTS: Questionnaires were returned by 32/35 (91%) centres approached. A total of 748 infusions were administered to 153 patients. After the first treatment course an excellent or good response occurred in 48/58 (83%) patients with luminal disease, and in 67/95 (71%) patients with fistulous disease (P < 0.05). After the first treatment course 108 (71%) patients received further infliximab therapy. At a mean follow-up of 29 months, 50% of patients had improved since baseline without requiring surgery for Crohn's disease. Steroid withdrawal was achieved in 25% of patients. Surgery had been performed in one-third of patients and was associated with lacking response to the first treatment course (P < 0.001) and with fistulous disease (P = 0.012). Co-medication with azathioprine favoured the initial response and steroid withdrawal (P < 0.05). One patient died from myocarditis; other adverse events were consistent with that seen in other studies of infliximab. CONCLUSIONS: The Austrian experience with infliximab for Crohn's disease is in general accordance with results from clinical trials and post-marketing studies from single centres. A substantial subgroup of patients appear to have a prolonged benefit from infliximab therapy.

Adult↗
PubMed2004

Type I interferons and their therapeutic role in Th2-regulated inflammatory disorders.

Cytokines are pleiotropic molecules showing a wide variety of biological functions on various cells and tissues. Several different cytokines exert similar and overlapping functions on certain cells. Interferons (IFNs) play a crucial role in human disease and consist of type I IFNs (IFN-alpha and IFN-beta) and type II IFN (IFN-gamma). The importance of type I IFNs in inflammation, immunoregulation and T cell responses has been recognised, and dendritic cells have recently been identified as the major source of type I IFNs. Type I IFNs are multifunctional immunomodulatory cytokines with profound effects on the cytokine cascade, including several anti-inflammatory properties. They favour both the induction of T helper (Th) 1 cytokines as well as the suppression of Th2 cytokines such as IL-13. Therefore, it is not unexpected that type I IFNs show promising clinical effects in Th2-dominated diseases such as ulcerative colitis and allergic asthma. These newly identified immunoregulatory and anti-inflammatory functions of type I IFNs may be of importance in the treatment of various chronic inflammatory disorders.

Animals↗
PubMed2003

Interleukin-18 attracts plasmacytoid dendritic cells (DC2s) and promotes Th1 induction by DC2s through IL-18 receptor expression.

In vivo evidence suggests that interleukin-18 (IL-18) shapes the development of adaptive immunity toward T-helper cell type 1 (Th1) responses. Monocyte-derived dendritic cells 1 (DC1s) preferentially induce a Th1 response, while plasmacytoid DC-derived DC2s have been linked to a Th2 response. We analyzed the role of IL-18 during the initiation phase of a Th response in vitro to elucidate the basis of these in vivo observations. IL-18 was constitutively released from DC1s, but not DC2s. Neutralization of IL-18 in coculture experiments of DC1s with allogeneic naive T lymphocytes did not alter the Th1/Th2 phenotype, while anti-IL-12 efficiently down-regulated the Th1 response. Unexpectedly, IL-18 receptor (IL-18R) alpha and beta chains were expressed on DC2 lineage. IL-18R expression was functional, as IL-18 induced chemotaxis in plasmacytoid DCs (pre-DC2s) and enhanced the allostimulatory capacity of IL-3-differentiated DC2s. Pre-DC2s exposed to IL-18 skewed the development of Th cells toward Th1 in coculture experiments of DC2s and allogeneic naive T cells, which was inhibited by IL-12 p70 neutralization. IL-18 might have a profound role during the initiation phase of an immune response by recruiting pre-DC2s and modulating the function of DC2s.

Apoptosis↗
PubMed2003

Anti-tumor necrosis factor-alpha monoclonal antibody therapy in severe alcoholic hepatitis.

BACKGROUND/AIMS: Severe alcoholic hepatitis (AH) is associated with high mortality. Tumor necrosis factor-alpha (TNFalpha) has been demonstrated to play an important role in its pathophysiology. METHODS: Twelve patients with biopsy-confirmed AH and a Maddrey discriminant factor >32 were treated with a single infusion of the anti-TNF monoclonal antibody Infliximab at a dose of 5mg/kg body weight. Serial measurements were made for various cytokines using specific enzyme-linked immunoassays (ELISA). In four patients, liver biopsy samples were available pretreatment and on day+28 of therapy. RESULTS: Ten of the 12 patients are alive at a median of 15 (12-20) months. Two patients died within 30 days from septicemia. Serum bilirubin levels, Maddrey score, neutrophil count and C-reactive protein fell significantly within the first month. There was an early, though not significant, decrease in plasma levels of proinflammatory cytokines (interleukins (IL)-1beta, IL-6, IL-8, interferon-gamma), whereas plasma levels of TNFalpha remained near the sensitivity limit of the assay throughout the treatment course. While TNFalpha mRNA expression in the liver did not change, expression of IL-8, a cytokine regulated mainly by TNFalpha, was almost absent on day+28. CONCLUSIONS: Our data suggest that randomized controlled trials of anti-TNF antibody in severe AH are warranted.

Antibodies, Monoclonal↗
PubMed2003

Sphingosine kinase-dependent migration of immature dendritic cells in response to neurotoxic prion protein fragment.

The concept that circulating dendritic cells mediate neuroinvasion in transmissible spongiform encephalopathies received strong support from recent observations that prion protein is expressed in myeloid dendritic cells. We observed that prion protein fragment 106-126 is a chemoattractant for monocyte-derived immature but not mature dendritic cells. Signaling events in chemotaxis involved enzymes downstream of G(q) protein and were inhibited by blockade of sphingosine kinase, suggesting transactivation of sphingosine-1-phosphate-dependent cell motility by prion protein.

Animals↗
PubMed2002

Role of IL-10 for induction of anemia during inflammation.

Anemia is frequently observed in patients suffering from chronic inflammatory disorders. Recent in vitro data suggest that Th2 cytokines, such as IL-10, could be involved in its pathogenesis. We analyzed 1) changes in hemoglobin values in 329 patients with chronic active Crohn's disease receiving the anti-inflammatory cytokine IL-10 as part of a randomized, double-blind, placebo-controlled study, 2) serum iron parameters in a subgroup of these patients (n = 54), and 3) the in vitro effects of IL-10 on ferritin transcription and translation in human monocytic cells (THP-1) by means of Northern blot and immunoprecipitation after metabolic labeling. Patients receiving higher doses of IL-10 developed anemia and presented with a dose-dependent increase of ferritin and soluble transferrin receptor levels, an indicator of iron restriction to erythroid progenitor cells. According to our in vitro data, hyperferritinemia may result from direct stimulation of ferritin translation by IL-10 in activated monocytic cells, most likely by cytokine-mediated reduction of the binding affinity of translational repressors, iron-regulatory proteins, to the 5'-untranslated region of ferritin mRNA. In patients, all observed changes were most pronounced at the end of therapy (day +29), and thereafter hemoglobin levels and serum iron parameters returned to baseline levels within 4 wk of follow-up. Our data demonstrate that IL-10 causes anemia in patients with inflammatory bowel disease which may be referred to the induction of imbalances in iron homeostasis by the cytokine, leading to hyperferritinemia and limited iron availability to erythroid progenitor cells, a condition typically seen in the anemia of chronic inflammation.

Adolescent↗
PubMed2002

Plasma levels of interleukin-18 and interleukin-18 binding protein are elevated in patients with chronic liver disease.

Interleukin 18 (IL-18) is a recently described proinflammatory cytokine. In mouse models it has been shown to play a key role in the development of liver injury. IL-18 binding protein (IL-18BP) is a naturally occurring antagonist of IL-18. In this study we investigated whether IL-18/IL-18BP levels are altered in patients with chronic liver disease (CLD). We measured IL-18 and IL-18BP plasma levels in 153 patients with CLD and 41 healthy controls by a specific ELISA. Plasma levels of IL-18 were significantly higher in CLD patients than in healthy controls. Cirrhotics had higher levels than noncirrhotics. IL-18 levels increased with disease progression. IL-18BP plasma levels paralled the increase of IL-18 with disease progression, except in stage Child C cirrhosis. IL-18 and IL-18BP levels were elevated independent of the etiology of CLD. IL-18 and IL-18BP correlated with laboratory parameters of inflammation and liver injury. Plasma levels of IL-18 and its antagonist, IL-18BP, are elevated in CLD and correlate with severity of disease. IL-18BP may not be sufficient to counteract the overwhelming proinflammatory response in end stage liver disease.

Adult↗
PubMed2002

Endotoxin and its binding proteins in chronic liver disease: the effect of transjugular intrahepatic portosystemic shunting.

BACKGROUND: Gut-derived endotoxin is insufficiently cleared by the diseased liver, and thus, is elevated in plasma of patients with chronic liver disease (CLD). Endotoxin action might be modified by binding to soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP), both of which have not yet been sufficiently studied in CLD. METHODS: Endotoxin, sCD14 and LBP have been determined in peripheral blood of 72 patients and 39 control subjects, and in portal and hepatic venous blood of 12 patients during transjugular intrahepatic portosystemic shunt (TIPS) implantation. RESULTS: Peripheral endotoxin (average 3-fold increased compared to controls), LBP, and sCD14 plasma levels were elevated in chronic liver disease irrespective of Child stage m, preserve/absence of cirrhosis or aetiology. LBP, and sCD14. Furthermore, endotoxin levels in the portal vein (38.1 +/- 6.1 pg/ml) were only slightly elevated compared to the hepatic vein (29.2 +/- 4.4 pg/ml), and peripheral endotoxin levels did not increase after TIPS. CONCLUSIONS: Decreased hepatocellular function rather than hepatic blood shunting might be responsible for endotoxemia. The elevation in LBP and sCD14 levels may be a consequence of endotoxemia.

Acute-Phase Proteins↗
PubMed2002

Splanchnic blood flow determination in patients with suspected chronic intestinal ischaemia.

Chronic intestinal ischaemia is characterized by postprandial abdominal pain and prominent weight loss, often leading to the first clinical suspicion of malignancy. After ruling out various gastrointestinal disorders, chronic intestinal ischaemia should be considered as a potential diagnosis. Besides the clinical picture, various non-invasive procedures are helpful in establishing the diagnosis. Whereas a plain abdominal radiography may show arterial calcifications, duplex ultrasonography is nowadays the leading diagnostic procedure for ruling out significant disease. Another promising and increasingly used technology is magnetic resonance angiography. Suspicious findings must be followed by the gold standard in diagnosis, namely splanchnic angiography. Since all these technologies provide only anatomical evidence of disease, functional imaging techniques assessing splanchnic blood flow after meal challenge using the invasive indocyanine green method may be helpful. However, further studies are needed in the use of this experimental technique in the workup of these patients.

Abdominal Pain↗
PubMed2002

Antitumour necrosis factor therapy in Crohn's disease.

The key role and contribution of various pro-inflammatory cytokines in common chronic inflammatory disorders such as inflammatory bowel disease (IBD) has been thoroughly investigated in recent years. Besides IL-1, TNF-alpha has been identified as one of the central immune mediators controlling inflammatory processes. Not surprisingly, neutralisation of these cytokines has been introduced into clinical research. Crohn's disease (CD) is one of the chronic inflammatory disorders where TNF-alpha seems to have a particularly important role. Neutralisation of this cytokine by specific antibodies, for example infliximab, has been shown recently to affect the clinical phenotype of this disorder. Other TNF-neutralising approaches such as etanercept have also been studied in patients with CD but with less successful outcomes. These new cytokine-targeting approaches have changed clinical medicine in the field of inflammatory disorders.

Antibodies, Monoclonal↗
PubMedDate not supplied

Interferon-alpha suppresses leptin levels: studies in interferon-alpha treated patients with hepatitis C virus infection and murine adipocytes.

Leptin is an adipocyte-derived protein, which signals the status of current energy stores and energy intake to the central nervous system. Interferon-alpha therapy is frequently associated with loss of appetite and weight reduction. In this study, we tested whether interferon-alpha is able to regulate leptin synthesis. We therefore determined leptin plasma concentrations in thirteen patients with chronic hepatitis C who were treated with 1 x 10(7) IU interferon-alpha daily, up to 21 days after initial treatment. Furthermore, leptin concentrations and messenger RNA levels were quantified in interferon-alpha-treated and untreated murine adipocytes. After reaching peak plasma levels at 12 hours, probably reflecting the circadian rhythm, leptin concentrations fell and were significantly lower after 14 days. They remained significantly decreased 17 and 21 days after the start of the interferon-alpha treatment. In murine adipocytes exposed to interferon-alpha, leptin secretion was significantly decreased while messenger RNA levels remained unchanged. Our data suggest that, in contrast to proinflammatory cytokines such as interleukin-1, interferon-alpha suppresses leptin secretion in adipose tissue. We therefore hypothesize that loss of weight and appetite in interferon-alpha-treated patients with chronic hepatitis C might not be due to an elevation of leptin resulting in signals of increased energy stores in the brain.

3T3 Cells↗