Herbert Tilg

..Targeting adiponectin could evolve as a major treatment concept especially for fatty liver diseases in the future...

..Endoplasmic reticulum stress and related signaling networks, (adipo)cytokines, and innate immunity are emerging as central pathways that regulate key features of NASH...

..Therefore, the capacity to induce apoptosis and neutralisation of TNF alone are insufficient to explain clinical efficacy of anti-TNF agents in human inflammatory bowel diseases...

..Therefore, the balance between pro- and anti-inflammatory acting cytokines/adipocytokines appears to play a key role in hepatic and systemic insulin action, and they are supposed to have important functions in the development of NAFLD...

..The European Crohn's Colitis Organization recently held its second annual meeting in Innsbruck, Austria dealing with both new basic and clinical developments in the field...

..Advanced age, extensive overweight and a number of features of the metabolic syndrome are associated with NAFLD severity. The cause of NAFLD is considered multifactorial with a substantial genetic component...

..Therefore, new weight-loss inducing agents are eagerly awaited to increase the percentage of obese people to benefit from weight reduction...

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..Importantly, transmission of the microbiota from these mice to healthy mice results in features of the metabolic syndrome. Available data suggest that the microbiota might play a role in the development of metabolic syndrome and obesity...

..Experienced gastroenterologists should be involved in the decision making for such a therapy to balance thoroughly the benefit/risk ratio for our patients...

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..Therefore, suppression of IL-17, as well as many other well-defined interactions of type I IFNs with the cytokine cascade, may contribute to virus-induced immunosuppression making the host vulnerable to bacterial and fungal attacks...

..Supplementary nonprocessed cereals may be beneficial in a certain subgroup of patients. With the recent developments in medical therapy, a balanced diet may allow many patients to become nutritionally autonomous...

..This review highlights new aspects in development of liver steatosis and the relevance of various cytokines and adipocytokines in NAFLD...

..As most findings in this field of research are based on mouse studies, the relevance to human biology requires further investigation...

..Mouse studies suggest a key role of adipose tissue-derived IL-6 in hepatic insulin resistance via modification of liver suppressor of cytokine signalling 3 (SOCS-3) expression...

..Whereas adiponectin has mainly anti-inflammatory functions, leptin, resistin and pre-B cell enhancing factor (PBEF)/Nampt/visfatin are considered as mainly pro-inflammatory mediators regulating metabolic and immune processes...

..The aim of these studies was to investigate changes of A-FABP during profound weight loss induced by laparoscopic adjustable gastric banding (LAGB)...

..This study investigated the activation state of the RANKL/OPG system and its association with bone loss in CLD...

..Excessive weight loss changes the adipose and liver expression profile of IL-1F members toward a more antiinflammatory direction...

..To further elucidate the relationship between pigment epithelium-derived factor and metabolic perturbations characteristic of obesity, we examined the effect of pronounced weight loss on serum levels of pigment epithelium-derived factor...

..However, there is only scarce knowledge on the functional role and regulation of endogenous adiponectin in non-fat tissues such as the liver under conditions of acute inflammation...

..These findings suggest a potent antiinflammatory role of imatinib by modulation of TNF-alpha production in monocytes/macrophages. This observation might be of therapeutic value for the treatment of TNF-mediated diseases...

..Macrophages, dendritic cells, and colonic epithelial cells might be additional sources of visfatin as determined by confocal microscopy. Visfatin can be considered a new proinflammatory adipocytokine...

..e. osteoclasts and monocytes). The latter represent the major source of dendritic cells (DC). Thus, we determined the immunomodulatory properties of zoledronic acid (ZA), a member of the latest generation of bisphosphonates...

..This is the first report demonstrating a potential role for this important cytokine/enzyme in inflammation-related bone disease...

..Measurement of visceral fat diameter by ultrasound is a novel and simple method to identify subjects with an increased risk for atherosclerosis within an obese population...

..CONCLUSIONS: Our results confirm the importance of IL-18 in the pathogenesis of IBD and suggest that especially in CD, IL-18BP might be produced in insufficient quantities to counteract the effects of endogenous IL-18...

..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...

..Currently, it is not clear which type of diet preferentially results in this common disease...

..Interference with cytokine pathways and/or administration of anti-inflammatory cytokines will be of major interest in the future therapy of many liver diseases...

..It remains unclear whether this is due to redistribution or active proliferation. The latter would require the upregulation of telomerase activity, whose regulation also remains unknown for Treg...

..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...

..Understanding this new exciting world of adipocytokines will be of importance in the development of novel therapies for obesity-associated diseases...

..The aim of the study was to investigate changes of adiponectin isoforms during profound weight loss and its relation to anthropomorphometric and metabolic parameters...

..CONCLUSION: Our data suggest that PBEF is of key importance in experimental hepatitis. Its specific inhibition might be considered a novel treatment option for inflammatory liver diseases...

..This might represent a fundamental link between over-nutrition and an impaired inflammatory immune response...

..MMPs and TIMPs are thought to play a major role in extensive reorganization of the adipose tissue in obesity...

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..Inflammatory bowel disease remains at the forefront of research in gastroenterology and recent findings will result in new treatment strategies...

..Our data suggest that IFNalpha down-regulates IL-17 expression and Th17 differentiation in vitro and in vivo. As a corollary, these effects might play a role in the mode of action of type I IFNs in the treatment of various diseases...

..Other neuropeptides arrest chemotaxis. Data support a priming role of the neuropeptide substance P in PrP(106-126)-induced migration of DCs involving neurokinin-1-receptors...

..CONCLUSION: IL-32 is a novel proinflammatory cytokine involved in HCV-associated liver inflammation/fibrosis. IL-32 is expressed by human hepatocytes and hepatoma cells and its expression is regulated by proinflammatory stimuli...

..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...

..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...

..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...

..In conclusion, adipocytokines are increasingly recognized as pleiotropic molecules involved in the pathophysiology of HCC, which might lead to therapeutic approaches targeting these mediators...

..These new cytokine-targeting approaches have changed clinical medicine in the field of inflammatory disorders...

..Our report provides evidence that MLN273 and, to a lesser degree, Bortezomib are both MDR-1-substrates, which might be relevant for drug-resistance in cancer...

..Many of the biological functions of this "cytokine-enzyme" have been characterized in the last years, however, its definite role in various metabolic, inflammatory and malignant diseases has yet to be defined...

..Advances in mucosal immunology have revealed a broad set of new therapeutic targets to resolve inflammation and symptoms in patients with inflammatory bowel diseases (IBD)...

..Understanding this rapidly growing family of mainly adipocyte-derived mediators might be of importance in the development of new therapies for obesity-associated diseases...

..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...

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..This report provides first evidence that Treg are potent suppressors of anti-GBM GN. Treg therefore might be of therapeutic value for the treatment of severe GN in humans...

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..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...

..Thus, Imatinib exerts potent immuno-modulatory effects in vitro and in vivo, which will be discussed together with their clinical relevance in detail throughout this review...

..The adipocytokine adiponectin has been proposed to play important roles in the regulation of energy homeostasis, insulin sensitivity and shows anti-inflammatory properties...

..Overall, this study provides evidence for a role of RANKL signaling in the pathogenesis of T2DM. If so, translation to the clinic may be feasible given current pharmacological strategies to lower RANKL activity to treat osteoporosis...

..Metabolic aspects have evolved as of key importance in experimental colitis and human IBD, and certain adipocytokines, autophagy, and ER stress might reflect the central players...

..These immune-modulatory effects of EPO may be of therapeutic relevance in infectious and inflammatory diseases...

..These newly identified immunoregulatory and anti-inflammatory functions of type I IFNs may be of importance in the treatment of various chronic inflammatory disorders...

..However, further studies are needed in the use of this experimental technique in the workup of these patients...

..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...

..Apoptotic cells in the mucosa were reduced on day 7. Our data point toward a novel efficacious treatment option in severe steroid-refractory UC and raise the need for controlled trials...

..Applying results from a murine model of colitis associated bone loss, the constellation of OPG and sRANKL regulation observed in our study raises the possibility that RANKL/OPG may contribute to the development of bone loss in IBD...

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..Independent of the stage of disease, abstinence from alcohol is the cornerstone of management. New treatment modalities for these diseases are eagerly awaited...

..We evaluated the safety of pegylated interferon alpha (PegIFN) and its role in induction of remission in patients with active ulcerative colitis, in a multicentre placebo controlled trial...

..CONCLUSION: Elevated plasma levels of sCD40L in CD patients supposedly reflect activation of functional CD40L in the intestine and might be a marker of intestinal inflammation...

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..Furthermore, because of their unknown aetiology, treatment is difficult, and evaluation of response is hampered by the natural tendency to spontaneous resolution and recurrence...

..We set out to investigate the effect of pronounced weight loss on circulating chemerin levels, a chemoattractant protein that also influences adipose cell function by paracrine and autocrine mechanisms...

..Interleukin 10 (IL-10) exerts anti-inflammatory actions by counteracting many biological effects of interferon gamma (IFN-gamma)...

..This regulatory pathway might be of relevance for the understanding of reactive thrombocytosis...

..Taken together, it seems likely that locally secreted interleukin-16 might serve to enhance the migration of cutaneous dendritic cells and optimize the response to foreign antigen encountering the skin...

..Recent data suggest that interleukin 6 (IL-6) and IL-6-regulated APPs are anti-inflammatory and immuno-suppressive, and may negatively regulate the acute phase response...

..CONCLUSION: Reduced hepatic expression of adiponectin and adipoRII might be of pathophysiological relevance in non-alcoholic fatty liver diseases...

..The new Glasgow alcoholic hepatitis score may represent a substantial improvement in clinical phenotyping and could catalyse the development of new treatments in severe alcoholic hepatitis...

..A substantial subgroup of patients appear to have a prolonged benefit from infliximab therapy...

..Hence, intestinal inflammation can originate solely from XBP1 abnormalities in IECs, thus linking cell-specific ER stress to the induction of organ-specific inflammation...

..We propose that activation of this pathway, with increased cell injury in NASH, also induces a periportal ductular reaction (DR) that could produce a profibrogenic stimulus...

..In patients with non-alcoholic steatohepatitis, lower levels of adiponectin were associated with higher grades of hepatic steatosis and necroinflammatory activity, suggesting a pathophysiological role for this adipokine in liver disease...