T. Andus
University of Regensburg
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Featured researches published by T. Andus.
World Journal of Surgery | 1998
Gerhard Rogler; T. Andus
Abstract. Cytokines play a central role in the modulation of the intestinal immune system. They are produced by lymphocytes (especially T cells of the Th1 and Th2 phenotypes), monocytes, intestinal macrophages, granulocytes, epithelial cells, endothelial cells, and fibroblasts. They have proinflammatory functions [interleukin-1 (IL-1), tumor necrosis factor (TNF), IL-6, IL-8, IL-12] or antiinflammatory functions [interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-10, IL-11, transforming growth factor β (TGFβ)]. Mucosal and systemic concentrations of many pro- and antiinflammatory cytokines are elevated in inflammatory bowel disease (IBD). An imbalance between proinflammatory and antiinflammatory cytokines was found for the IL-1/IL-1ra ratio in the inflamed mucosa of patients with Crohn’s disease, ulcerative colitis, diverticulitis, and infectious colitis. Furthermore, the inhibition of proinflammatory cytokines and the supplementations with antiinflammatory cytokines reduced inflammation in animal models, such as the dextran sulfate colitis (DSS) model, the trinitrobenzene sulfonic acid (TNBS) model, or the genetically engineered model of IL-10 knockout mice. Based on these findings a rationale for cytokine treatment was defined. The first clinical trials using neutralizing monoclonal antibodies against TNFα (cA2) or the antiinflammatory cytokine IL-10 have shown promising results. However, many questions must be answered before cytokines can be considered standard therapy for IBD.
Clinical and Experimental Immunology | 1997
G Kojouharoff; W Hans; Florian Obermeier; Daniela N. Männel; T. Andus; Jürgen Schölmerich; V Gross; Werner Falk
The cytokines TNF and IL‐1 have been implicated as mediators of the inflammatory processes in patients with inflammatory bowel disease (IBD). To investigate the role of these cytokines in mucosal inflammation we used anti‐cytokine strategies in a mouse model of acute and chronic colitis. Mice which received 5% dextran sulphate sodium (DSS) in their drinking water showed signs of acute colitis on day 4, with severe weight loss and bloody diarrhoea. Chronic colitis was established after four cycles of feeding 5% DSS for 7 days and water for 10 days, with the mice showing diarrhoea but no weight loss. In acute colitis, treatment with anti‐IL‐1 reagents, anti‐TNF MoAb, or dexamethasone (DEX) led to aggravation. By contrast, in chronic colitis, treatment of mice with several IL‐1 activity‐inhibiting reagents failed to show significant effects, whereas anti‐TNF MoAb or DEX significantly reduced the colitis. We conclude that in acute colitis IL‐1 and TNF are beneficial, whereas in chronic colitis, TNF but not IL‐1 seems to play a major role in perpetuation of chronic inflammation.
The American Journal of Gastroenterology | 2002
Hans Herfarth; Florian Obermeier; T. Andus; Gerhard Rogler; Susanna Nikolaus; Tanja Kuehbacher; Stefan Schreiber
was normal (138 10/ l). Two years later he was still positive for hepatitis B surface antigen, HBeAg, and HBV DNA measured by polymerase chain reaction; the ALT activity was elevated to 54 IU/L (normal 40). Hepatitis C virus infection and autoaggressive disorders were excluded. Physical examination revealed no deviation from normal state; there were no hematological disturbances (platelet count 149 10/ l, red blood cell [RBC] count 4.42 10/ l, white blood cell [WBC] count 4.9 10/ l). Liver ultrasound and Doppler sonography revealed no abnormalities. We decided to treat him with lamivudine at a dose of 100 mg/day (3 mg/kg/day). After a month of treatment, decline in platelets to 35 10/ l was observed. WBC and RBC counts were within normal ranges; ALT activity was 34 IU/L. Lamivudine therapy was discontinued; he received immunoglobulin for 5 days and the platelet count returned to normal (158 10/ l). During 3 months of observation after lamivudine therapy discontinuation the platelet count was in the normal range. The boy still replicated HBV (HBeAg and HBV DNA positive) and ALT activity increased to 68 IU/L. We therefore decided to administer lamivudine again at a dose of 50 mg/day. After 3 days of therapy the platelet count decreased to 55 10/ l (WBC and RBC counts were within normal ranges). Antiplatelet and antinuclear antibodies were not detected. Marrow specimens showed normal cellularity and increased megakaryocytes. The boy had recovery of platelets a week after lamivudine discontinuation without any concomitant treatment; a month later the platelet count was 137 10/ l. At this moment, to our knowledge, thrombocytopenia during lamivudine therapy has not been reported. Possible causes of cytopenia during antiviral therapy (e.g., interferon) in patients with chronic hepatitis B are mechanisms such as bone marrow suppression (7), immune-mediated toxicity of the drug (7, 8), or increased sequestration of platelets in the liver and spleen (9). We speculate that the observed thrombocytopenia in our patient treated with lamivudine could be the consequence of immune peripheral destruction of platelets, mainly in the spleen, rather than myelosuppression. The results of this study indicate that, despite confirmed lamivudine therapy safety in adults, serious adverse effects can occur, and this drug should be prescribed for children only by physicians experienced in its use, who should be cautious about the hematologically adverse effects of this drug.
Gastroenterology | 1995
V. Gross; T. Andus; Rosemarie Daig; Elisabeth Aschenbrenner; Jürgen Schölmerich; Werner Falk
BACKGROUND/AIMSnInterleukin (IL) 8 is a major neutrophil-activating cytokine synthesized by intestinal epithelial cell lines. The aim of this study was to improve the understanding of the regulation of IL-8 synthesis by investigating the roles of protein kinase C (PKC), protein kinase A (PKA), and protein tyrosine kinase (PTK) in the induction of IL-8.nnnMETHODSnHT-29 cells were stimulated with IL-1 beta or tumor necrosis factor alpha (TNF-alpha) together with activators or inhibitors of PKC and PKA or with inhibitors of PTK. The presence of IL-8 protein was detected by enzyme-linked immunosorbent assay and that of IL-8 messenger RNA by Northern blotting and in situ hybridization.nnnRESULTSnTNF-alpha and IL-1 beta dose-dependently induced IL-8 production in HT-29 cells. Activation of PKC by phorbol myristate acetate also stimulated IL-8 production; however, the effects of IL-1 beta or TNF-alpha did not require PKC, as shown by the PKC inhibitor staurosporin or PKC depletion. Stimulation of PKA by forskolin or inhibition by H89 or H7 had no influence on the synthesis of IL-8. However, induction of IL-8 by IL-1 beta or TNF-alpha was reduced by the PTK inhibitors herbimycin (by 79% or 89%, respectively) and genistein (by > 95%).nnnCONCLUSIONSnThe synthesis of IL-8 is stimulated in HT-29 cells by IL-1 beta or TNF-alpha. This stimulation is independent from PKC or PKA but depends on protein tyrosine phosphorylation.
Clinical and Experimental Immunology | 2001
Martin Hausmann; T. Spöttl; T. Andus; G. Rothe; Werner Falk; Jürgen Schölmerich; Hans Herfarth; Gerhard Rogler
Macrophages play a central role during the pathogenesis of inflammation. In normal intestinal mucosa surface expression of typical macrophage markers such as CD14, CD16, CD11b or T‐cell co‐stimulatory molecules such as CD80 or CD86 is low indicating anergy and low pro‐inflammatory activity of these cells. During inflammatory bowel disease (IBD) the mucosa is invaded by a population of macrophages displaying these markers, secreting higher cytokine levels and representing an activated cell population. CD33+ cells (macrophages) were isolated from normal and Crohns disease mucosa and mRNA was isolated by polyT magnetic beads. A subtractive screening was performed subtracting mRNA from normal macrophages from those of Crohns disease macrophages. Oxidative burst activity was determined by flow cytometry. Seventy clones were obtained by the subtractive mRNA screening. Sequencing showed >u200a99% homology to mRNA of monocyte chemoattractant protein‐1 (MCP‐1) for three clones. Five clones obtained by subtraction revealed >u200a99% homology to mRNA of cytochrome b (subunit gp91). Differential expression of the cytochrome b subunit gp91 and the cytosolic NADPH oxidase subunit p67 was confirmed by RT‐PCR and ‘virtual’ Northern blots. The fluorescence ratio of stimulated versus unstimulated cells was 0·9u2003±u20030·16 in control macrophages indicating a lack of oxidative burst activity. In Crohns disease this ratio was significantly increased to 1·80u2003±u20030·8 (Pu2003=u20030·004) confirming the molecular data. In conclusion NADPH oxidase mRNA is down‐regulated or absent in macrophages from normal mucosa correlating with a lack of oxidative burst activity. In IBD macrophage‐oxidative burst activity is increased and NADPH oxidase mRNA induced. Inhibition of NADPH oxidase could be a new therapeutical target in IBD and reduce mucosal tissue damage in active IBD.
Alimentary Pharmacology & Therapeutics | 2003
T. Andus; Frank Klebl; Gerhard Rogler; Nicole Bregenzer; Jürgen Schölmerich; Rainer H. Straub
Background :u2002Dehydroepiandrosterone is a steroid hormone used as an ‘over‐the‐counter’ drug in the USA. Treatment with dehydroepiandrosterone was effective in randomized controlled trials in patients with systemic lupus erythematosus. Dehydroepiandrosterone sulphate concentrations are decreased in patients with inflammatory bowel disease. Dehydroepiandrosterone inhibits nuclear factor‐κB and the secretion of interleukin‐6 and interleukin‐12 via the peroxisome proliferator‐activated receptor α.
American Journal of Hypertension | 1999
Heribert Schunkert; Hans-Werner Hense; T. Andus; Günter A.J. Riegger; Rainer H. Straub
Endogenous dehydroepiandrosterone sulfate (DHEAS) levels have been reported to be positively related to blood pressure levels. To further analyze this association, we quantified DHEAS in middle-aged subjects (mean age +/-SEM: 57.8+/-0.1 years) of a population-based sample (n = 646). DHEAS levels were higher in hypertensive as compared with normotensive individuals (1.26+/-0.04 v. 1.09+/-0.03 microg/mL, P = .01). After adjustment for age, gender, and body mass index, DHEAS levels were significantly related to systolic blood pressure (P = .01). In addition, in a subgroup of individuals without antihypertensive medication adjusted DHEAS levels were significantly related to systolic and diastolic blood pressure (n = 461; P<.05, both). DHEAS levels were also related to aldosterone (r = 0.15; P = .002) and androstenedione (its main metabolite; r = 0.66; P<.001) but not to renin levels. Like DHEAS, aldosterone, but not androstenedione, was significantly related to blood pressure levels and hypertension status. In a regression analysis that accounted for aldosterone and renin levels, both DHEAS and aldosterone kept their significant relationships with systolic blood pressure levels. Taken together, we observed a consistent positive association between endogenous DHEAS and systolic blood pressure levels that was independent of other, similarly regulated, adrenal steroids.
International Journal of Colorectal Disease | 2004
Hans Herfarth; V. Gross; T. Andus; I. Caesar; H. Vogelsang; G. Adler; H. Malchow; A. Petri; Michael Gierend; Jürgen Schölmerich
Background and aimsThe nonsystemic steroid budesonide has been used to treat active ileocecal and ileocolonic Crohns disease (CD). This study investigated the optimal budesonide dose using a pH-dependent release formulation. The goal of treatment was the remission of CD (CDAI <150) within 6xa0weeks of treatment.Patients and methodsThe study was of randomized, double-blind, dose-finding design. Patients with active CD ileocolitis without steroid pretreatment were treated with 3×2xa0mg (n=39), 3×3xa0mg (n=33), or 3×6xa0mg (n=32) oral pH-modified released budesonide daily.ResultsThe remission rates after 6xa0weeks were 36% with 3×2xa0mg, 55% with 3×3xa0mg, and 66% with 3×6xa0mg. Significantly more patients were in remission while treated with 3×xa06mg than with 3×2xa0mg budesonide/day. Subgroup analyses revealed that patients with high disease activity (CDAI ≥ 300) or ileocolonic disease with disease manifestation distal to the transverse colon responded better to the highest budesonide dose.ConclusionOral pH-modified released budesonide shows a dose-dependent effectiveness in patients with active ileocolonic CD. In the majority of patients 9xa0mg budesonide per day is sufficient. However, in patients with highly active disease or ileal disease with distal colonic manifestation higher doses of budesonide could increase the therapeutic response
Digestive Diseases and Sciences | 2003
T. Andus; V. Gross; Inka Caesar; H.J. Schulz; Herbert Lochs; W.D. Strohm; M. Gierend; A. Weber; K. Ewe; Jürgen Schölmerich
Glucocorticosteroids (GCS) are established in the treatment of active Crohns ileitis and ileocolitis. Recently, the topical steroid budesonide was found to be effective in untreated patients with Crohns disease (CD) causing less side effects than conventional GCS. No clinical data have been reported about the effects of switching from conventional GCS to budesonide in terms of side effects and disease activity. The primary aim of this study was to evaluate the development of side effects after switching from conventional GCS treatment to Eudragit L-coated budesonide (pH-modified release formulation) in patients taking 5–30 mg prednisolone equivalent per day for at least two weeks. In all, 178 patients with active CD (N = 88) or CD in remission during GCS treatment (N = 90) were included. Conventional GCS treatment was tapered down during a maximum of three weeks, with simultaneous intake of 3 × 3 mg budesonide. Thereafter, patients received 3 × 3 mg budesonide alone for six weeks. GCS-related side effects, disease activity and adverse events were documented at study entry and after 0, 2, 4, and 6 weeks of budesonide treatment. The percentage of patients with GCS-related side effects decreased from 65.2% (intention-to-treat-population) at entry to 43.3% (P < 0.0001) at the end of the trial. The total number of GCS-related side effects decreased significantly from 269 to 90. Of the patients who entered the study with active disease under conventional GCS therapy, 38.6% were in remission at the end of the study. Of the patients who entered the study with CD in remission, 78% stayed in remission after switching from conventinal GCS to budesonide. In conclusion, switching from conventional GCS treatment to budesonide leads to a significant reduction of GCS related side effects in patients with CD without causing rapid deterioration of the disease.
Gastroenterology | 2002
Martin Hausmann; Stephan Kiessling; S. Mestermann; G. Webb; T. Spöttl; T. Andus; Jürgen Schölmerich; Hans Herfarth; K. Ray; Werner Falk; Gerhard Rogler