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A Jörres

Publications and source records attributed to A Jörres.

At least 19 recordsLinked to original sources
PubMed2007

Role of mesothelial cell-derived granulocyte colony-stimulating factor in interleukin-17-induced neutrophil accumulation in the peritoneum.

Recent studies suggest that peritoneal CD4(+) T lymphocytes may control recruitment of polymorphonuclear leukocytes (PMN) during peritonitis by an interleukin-17 (IL-17)-dependent mechanism. IL-17 and granulocyte colony-stimulating factor (G-CSF) have been proposed to form an axis that regulates PMN transmigration. Here we report on the role of G-CSF released by human peritoneal mesothelial cells (HPMCs) in IL-17A-mediated peritoneal PMN accumulation. In vitro exposure of HPMCs to IL-17A resulted in a time- and dose-dependent release of G-CSF. This effect was related to the induction of G-CSF mRNA and mediated through the nuclear factor-kappaB (NF-kappaB) pathway. The novel observation was that IL-17A-stimulated NF-kappaB activation in HPMCs followed a biphasic profile, with an early induction (45 min), followed by the return to basal levels (90 min), and a delayed induction (3 h). Tumor necrosis factor alpha synergistically amplified IL-17A-induced G-CSF production by enhanced NF-kappaB activation and through stabilization of G-CSF mRNA. Intraperitoneal (i.p.) administration of IL-17A in Balb/c mice resulted in increased local levels of G-CSF and selective PMN accumulation. Administration of anti-G-CSF blocking antibody before IL-17A injection significantly reduced the IL-17A-triggered PMN infiltration. This effect occurred despite increased i.p. levels of PMN-specific chemokines KC and macrophage inflammatory protein-2 seen in animals treated with anti-G-CSF antibody. These data demonstrate that the mesothelium-derived G-CSF plays an important role in IL-17A-induced PMN recruitment into the peritoneum.

Animals↗
PubMed2004

Interleukin-17: a mediator of inflammatory responses.

Interleukin-17 (IL-17) is a prototype member of a new cytokine family with six species identified to date. IL-17 is secreted mainly by activated CD4(+) and CD8(+) T lymphocytes, while its receptor is distributed ubiquitously. IL-17 has been classified as a proinflammatory cytokine because of its ability to induce the expression of many mediators of inflammation, most strikingly those that are involved in the proliferation, maturation and chemotaxis of neutrophils. Increased levels of IL-17 have been associated with several conditions, including airway inflammation, rheumatoid arthritis, intraperitoneal abscesses and adhesions, inflammatory bowel disease, allograft rejection, psoriasis, cancer and multiple sclerosis. This review provides an overview of IL-17 activities, concentrating on those that lead to neutrophil recruitment.

Animals↗
PubMed2002

Extracorporeal treatment strategy in acute renal failure.

The mortality of acute renal failure remains high (around 50-70%) despite manifold improvements in terms of techniques and equipment for renal replacement therapies as well as patient monitoring and intensive care support. At present, it is not clear if the method chosen for renal replacement therapy, i.e. intermittent hemodialysis or continuous hemofiltration, might impact on the outcome of these patients. Whilst earlier retrospective studies suggested that CVVH might result in better survival and renal recovery in acute patients, recent prospective studies indicated that this may not be the case or, conversely, outcomes may be better with IHD. These studies were, however, not evenly randomised in terms of illness severity or were too small to produce conclusive results. In addition, a meta-analysis of 9 published prospective studies in 692 pts. indicated a similar mortality with CVVH vs. IHD. Some of the studies enrolled for this meta-analysis, however, suffered from methodological and/or randomisation problems, thus this important question remains to date unanswered. Typically, CVVH is chosen for treating patients with hemodynamic instability and volume overload. In such cases, however, CVVH should be performed with a filtrate volume of at least 35 ml/kg body weight per hour as this was shown to be associated with better survival as compared to smaller filtrate volumes. A second controversy exists to date whether the choice of the dialyzer membrane might be of relevance for the outcome of patients with acute renal failure. Earlier studies indicated that the use of biocompatible membranes in these patients may result in improved patient survival and renal recovery. More recently, however, similar studies could not confirm these results. Another meta-analysis of controlled prospective trials (671 patients in 7 separate studies) calculated a relative mortality risk of 1.01 for cuprophan vs. biocompatible membranes. Thus, the choice of the dialyzer membrane should be based on individual assessment rather than treatment bias.

Acute Kidney Injury↗
PubMed2002

Acute renal failure. Extracorporeal treatment strategies.

The mortality for acute renal failure remains to be high (around 50-70%) despite manifold improvements in terms of techniques and equipment for renal replacement therapies as well as patient monitoring and intensive care support. At present, it is not clear if the method chosen for renal replacement therapy, i.e. intermittent hemodialysis or continuous hemofiltration, might impact significantly on the outcome of these patients. Whilst earlier retrospective studies suggested that CVVH might result in better survival and renal recovery in acute patients, recent prospective studies were unable to confirm these findings. These studies were, however, not evenly randomised in terms of severity of illness or too small to produce conclusive results. In clinical routine CVVH is typically chosen for treating patients with hemodynamic instability and volume overload. If one decides to perform CVVH, however, a filtrate volume of at least 35 ml/kg body weight and hour should be used as this was shown to be associated with better survival as compared to smaller filtrate volumes. A second controversy exists to date whether the choice of the dialyzer membrane might be of significant relevance for the outcome of patients with acute renal failure. Earlier studies indicated that the use of biocompatible membranes in these patients may result in improved patient survival and renal recovery. More recently, however, these results could not be confirmed by larger randomized, prospective clinical studies. Thus, the choice of the dialyzer membrane should be based on individual assessment rather than treatment bias.

Acute Kidney Injury↗
PubMed2001

Fatal acute diclofenac-induced immune hemolytic anemia.

We report the case of a 72-year-old woman who developed fatal immune hemolytic anemia with multisystem organ failure and shock caused by diclofenac-dependent red blood cell autoantibodies. The patient described dramatically illustrates the potential severity of this adverse reaction and emphasizes the need for increased awareness of this complication of drug therapy.

Aged↗
PubMed2001

Synthesis of C-X-C and C-C chemokines by human peritoneal fibroblasts: induction by macrophage-derived cytokines.

Leukocyte accumulation during peritonitis is believed to be controlled by chemotactic factors released by resident peritoneal macrophages or mesothelial cells. Recent data indicate, however, that in many tissues fibroblasts play a key role in mediating leukocyte recruitment. We have therefore examined human peritoneal fibroblasts (HPFBs) for the expression and regulation of C-X-C and C-C chemokines. Quiescent HPFBs secreted monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8 constitutively. This release could be dose-dependently augmented with the pro-inflammatory cytokines IL-1beta and tumor necrosis factor-alpha. Stimulated IL-8 production reached a plateau within 48 hours while MCP-1 continued to accumulate throughout 96 hours. Induction of IL-8 and MCP-1 synthesis by HPFBs was also triggered by peritoneal macrophage-conditioned medium. This effect was partly related to the presence of IL-1beta as demonstrated by IL-1 receptor antagonist inhibition. Pretreatment of HPFBs with actinomycin D or puromycin dose-dependently reduced cytokine-stimulated IL-8 and MCP-1 secretion, which suggested de novo chemokine synthesis. Indeed, exposure of HPFBs to IL-1beta and tumor necrosis factor-alpha produced a significant up-regulation of IL-8 and MCP-1 mRNA. This effect was associated with the rapid induction of nuclear factor-kappaB binding activity mediated through p65 and p50 subunits, and with a transient increase in the mRNA expression for RelB and inhibitory protein kappaB-alpha proteins. These data indicate that peritoneal fibroblasts are capable of generating large quantities of chemokines under a tight control of nuclear factor-kappaB/Rel transcription factors. Thus, peritoneal fibroblast-derived chemokines may contribute to the intraperitoneal recruitment of leukocytes during peritonitis.

Cells, Cultured↗
PubMed2001

Innovative approaches to the preservation of the peritoneal membrane: from bench to bedside.

The functional integrity of the peritoneal membrane is of critical importance for the long-term success of peritoneal dialysis therapy. In addition to water and solute transport properties, the function of the membrane encompasses complex interactions with immune cells, invading microorganisms, and dialysis fluid components. During chronic peritoneal dialysis, intraperitoneal homeostasis is threatened by the repeated exposure to an unphysiologic environment that is created by the instilled solutions. Whereas their acidic pH and hyperosmolality were shown to primarily induce alterations of acute cell function, long-term peritoneal function might be affected by the repeated exposure to high concentrations of glucose and glucose degradation products. In addition to their intrinsic toxicity, these might induce or accelerate glycation processes, such as formation and deposition of advanced glycation end products in the peritoneal membrane. Presently, a new generation of dual-chambered peritoneal dialysis solutions combining the advantages of neutral pH and reduced glucose degradation products content is being introduced into clinical practice. In addition to an improved in vitro biocompatibility profile, emerging clinical trials of these novel solutions indicate that they might also improve the host defense status, membrane transport characteristics, ultrafiltration capacity, and effluent markers of peritoneal membrane integrity, while being safe and effective in correcting uremic acidosis and providing relief of inflow pain. Overall, these findings suggest that these new dialysis solutions might constitute an important step toward better preservation of long-term peritoneal membrane function during peritoneal dialysis.

Dialysis Solutions↗
PubMed2000

IL-17 stimulates intraperitoneal neutrophil infiltration through the release of GRO alpha chemokine from mesothelial cells.

IL-17 is a newly discovered cytokine implicated in the regulation of hemopoiesis and inflammation. Because IL-17 production is restricted to activated T lymphocytes, the effects exerted by IL-17 may help one to understand the contribution of T cells to the inflammatory response. We investigated the role of IL-17 in leukocyte recruitment into the peritoneal cavity. Leukocyte infiltration in vivo was assessed in BALB/Cj mice. Effects of IL-17 on chemokine generation in vitro were examined in human peritoneal mesothelial cells (HPMC). Administration of IL-17 i.p. resulted in a selective recruitment of neutrophils into the peritoneum and increased levels of KC chemokine (murine homologue of human growth-related oncogene alpha (GROalpha). Pretreatment with anti-KC Ab significantly reduced the IL-17-driven neutrophil accumulation. Primary cultures of HPMC expressed IL-17 receptor mRNA. Exposure of HPMC to IL-17 led to a dose- and time-dependent induction of GROalpha mRNA and protein. Combination of IL-17 together with TNF-alpha resulted in an increased stability of GROalpha mRNA and synergistic release of GROalpha protein. Anti-IL-17 Ab blocked the effects of IL-17 in vitro and in vivo. IL-17 is capable of selectively recruiting neutrophils into the peritoneal cavity via the release of neutrophil-specific chemokines from the peritoneal mesothelium.

Animals↗
PubMed2000

Patients' expressions of complaints as a predictor of the course of acute hepatitis A.

OBJECTIVE: Physical complaints, emotional states, liver, and immune parameters were investigated as possible indicators of the course of hepatitis A. METHODS: Forty-seven patients with hepatitis A were studied by means of the Giessen-Complaint-Inventory (GBB) and the Berlin Mood Questionnaire (BSF), as well as by taking into account their typical liver parameters and the following immune parameters: alphaInterferon (alphaIFN), soluble Interleukin 2 receptor (sIL-2R), Interleukin 6 (IL-6), Interleukin 1 receptor antagonist (IL-1Ra), and Immunoglobulin M or G (IgM, IgG). Two hundred twenty-nine medical students and a representative German sample (n = 1557, Braehler et al.) served as controls. RESULTS: We found that the initial degree of change in permeability of the liver cells, complaints about abdominal symptoms, and extent of depressive mood were able to predict the length of hospital stay. Patients with the initial, more pronounced liver damage, as well as patients who articulated less subjective impairment proved to have a longer course of illness. Those patients who needed a significantly longer time for recovery report, at admission, very few complaints-fewer than even the normal population. We were not, however, able to demonstrate a significant difference in the investigated immune parameters. CONCLUSION: A certain denial tendency seems to be harmful with respect to the recovery process and the immunological competence in the course of hepatitis A.

Acute Disease↗
PubMed2000

Administration of prostacyclin after liver transplantation: a placebo controlled randomized trial.

The shortage of suitable organs for liver grafts is responsible for the use of marginal donors for liver transplantation (OLT). If these liver grafts function poorly initially after OLT, a supportive therapy is necessary. The purpose of this study was to evaluate the effects of prostacyclin (PGI2) on postoperative liver graft function after OLT. A total of 30 adult recipients of primary OLT were randomized to either receive PGI2 (4 ng/kg per min body weight, n = 15) or a placebo for 6 d. To evaluate regional splanchnic oxygenation a fiberoptic pulmonary-artery catheter was inserted into a hepatic vein and the difference between mixed venous oxygen content and hepatic venous oxygen content was determined (deltaO2). Measurements were performed directly after transplantation and at 6, 12, 24 and 48 h postoperatively. A significant correlation between deltaO2 and the level of transaminases (ALT/AST) was observed 24 and 48 h after transplantation (p < 0.05). PGI2 treatment induced a significant decrease in deltaO2 after 24 and 48 h after reperfusion (p < 0.05). Peak AST levels tended to be lower in the PGI2 treatment group (418 +/- 99 vs. 638 +/- 156 U/L, p < 0.1). These results suggest that administration of PGI2 after OLT improves hepatic-splanchnic oxygenation and may thereby reduce reperfusion injury after OLT.

Adult↗
PubMed2000

Nightly intermittent peritoneal dialysis: targets and prescriptions.

Adequate peritoneal dialysis can be achieved in most ESRD patients, provided that the prescription is individualized according to body surface area, body weight, residual renal function, and peritoneal transport characteristics. NIPD is particularly indicated in patients with significant residual renal function or those with a high-transport peritoneal membrane (accounting for about 10% of the PD patient population). "Dry day" NIPD reduces small-solute clearance by at least 10%-15% and middle-molecule clearance by almost 50%. Thus, most NIPD patients without residual renal function are at risk of inadequate treatment. The target dose of NIPD should be a weekly Kt/V of at least 2.2 and a weekly total creatinine clearance of 66 L/1.73 m2. However, the periodic clinical evaluation of patients should have priority over the mere achievement of a numerical clearance target.

Automation↗
PubMed2000

Glucose degradation products and the peritoneal mesothelium.

Conventional heat-sterilized, glucose-based peritoneal dialysis (PD) fluids contain significant amounts of glucose degradation products (GDPs) such as aldehydes and dicarbonyl compounds (glyoxal, methylglyoxal). These GDPs have been shown to impair cell functions in various in vitro experimental models. In peritoneal mesothelial cells, GDPs dose-dependently inhibit cell proliferation and mediator synthesis. In addition, some GDPs potently promote generation of advanced glycation end-products (AGEs). Immunohistochemistry finds AGEs in the peritoneal membrane of chronic continuous ambulatory peritoneal dialysis (CAPD) patients, suggesting that peritoneal AGE accumulation may be involved in chronic peritoneal fibrosis. The formation of GDPs might be prevented by filter-sterilization of PD fluids. Another option is to separate the glucose and the buffer system in dual-chambered or multi-chambered containers. In these systems, the glucose is kept in a separate compartment at high concentration and very low pH-both conditions being known to minimize the degree of glucose decomposition during autoclaving. Initial experimental evidence suggests that these novel, multi-chambered fluids significantly improve in vitro biocompatibility; however, the clinical relevance of these results remains to be established in clinical trials.

Dialysis Solutions↗
PubMed2000

First in vitro and in vivo experiences with Stay-Safe Balance, a pH-neutral solution in a dual-chambered bag.

In addition to low pH and high osmolarity, glucose degradation products (GDPs) are considered to play a major role in the bioincompatibility of peritoneal dialysis fluids (PDFs). The formation of GDPs can be reduced by separating the glucose component of the solution (kept at very low pH) from the lactate component of the solution (kept at alkaline pH) during sterilization and storage. This development has been achieved by the use of a dual-chambered bag. Immediately before infusion, the seam between the two chambers is opened, and the contents are mixed. The result is a fluid with a more physiologic pH in the range 6.8 - 7.4. Concentrations of 3-deoxyglucosone (3-DG), methylglyoxal (MG), acetaldehyde (AA), and formaldehyde (FA) in Stay-Safe Balance (Fresenius Medical Care, Bad Homburg, Germany) were remarkably reduced when compared to conventional PD solution [conventional PDF (1.5% glucose): 172 micromol/L, 6 microLmol/L, 152 micromol/L, and 7 micromol/L respectively; Stay-Safe Balance (1.5% glucose): 42 micromolL, < 1 micromol/L, < 2 micromol/L, and < 3 micromol/L respectively; conventional PDF (4.25% glucose): 324 micromol/L, 10 micromol/L, 182 micromol/L, and 13 micromol/L respectively; Stay-Safe Balance (4.25% glucose): 60 micromol/L, < 1 micromol/L, < 2 micromol/L, and < 3 micromol/L respectively). Human peritoneal mesothelial cells (HPMCs) were exposed to a control solution, a conventional PDF [CAPD 2, 1.5% glucose (Fresenius Medical Care, Bad Homburg, Germany)], and Stay-Safe Balance, either in a co-incubation model (24-hour PDF exposure) or in a pre-incubation model (30-min PDF exposure), followed by 24-hour recovery in culture medium. Interleukin-1beta (IL-1beta)-stimulated (1 ng/mL) IL-6 secretion from HPMCs was assessed by ELISA. Exposure of HPMCs to conventional PDF resulted in a significant reduction in IL-6 release, which was fully restored following exposure to Stay-Safe Balance. In addition to the short-term investigations, long-term in vitro studies were also carried out. All fluids had near-neutral pH and were changed every second day. After 1, 3, 5, 7, 10, and 13 days of exposure, cell viability was assessed. Whereas exposure to conventional PDF resulted in a significant reduction in HPMC viability after just 3 - 5 days, no significant toxicity of filter-sterilized or dual-chambered fluid was observed for up to 13 days. An observational study with 9 patients suggested that the efficacy of Stay-Safe Balance is equivalent to that of conventional solution. However, even short-term treatment (8+/-1 weeks) with this more biocompatible solution seems to improve mesothelial cell mass as indicated by a rise in cancer antigen 125 (CA125) from a baseline of 47+/-37 U/min to 172+/-90 U/min. Our data indicate that Stay-Safe Balance may help to better preserve peritoneal membrane cell function. An ongoing European multicenter study is expected to confirm these results.

Cells, Cultured↗
PubMed1999

Haemodialysis-membrane biocompatibility and mortality of patients with dialysis-dependent acute renal failure: a prospective randomised multicentre trial. International Multicentre Study Group.

BACKGROUND: There is controversy as to whether haemodialysis-membrane biocompatibility (ie, the potential to activate complement and neutrophils) influences mortality of patients with acute renal failure. We did a prospective randomised multicentre trial in patients with dialysis-dependent acute renal failure treated with two different types of low-flux membrane. METHODS: 180 patients with acute renal failure were randomly assigned bioincompatible Cuprophan (n=90) or polymethyl-methacrylate (n=90) membranes. The main outcome was survival 14 days after the end of therapy (treatment success). Odds ratios for survival were calculated and the two groups were compared by Fisher's exact test. Analyses were based on patients treated according to protocol (76 Cuprophan, 84 polymethyl methacrylate). FINDINGS: At the start of dialysis, the groups did not differ significantly in age, sex, severity of illness (as calculated by APACHE II scores), prevalence of oliguria, or biochemical measures of acute renal failure. 44 patients (58% [95% CI 46-69]) assigned Cuprophan membranes and 50 patients (60% [48-70]) assigned polymethyl-methacrylate membranes survived. The odds ratio for treatment failure on Cuprophan compared with polymethyl-methacrylate membranes was 1.07 (0.54-2.11; p=0.87). No difference between Cuprophan and polymethyl-methacrylate membranes was detected when the analysis was adjusted for age and APACHE II score. 18 patients in the Cuprophan group and 20 in the polymethyl-methacrylate group had clinical complications of therapy (mainly hypotension). INTERPRETATION: There were no differences in outcome for patients with dialysis-dependent acute renal failure between those treated with Cuprophan membranes and those treated with polymethyl-methacrylate membranes.

APACHE↗
PubMed1999

Local liberation of cytokines during liver preservation.

In order to investigate locally produced mediators during the process of organ storage in liver transplantation, we collected the liver preservation solution effluent of 15 transplanted livers and compared it with serum samples taken preoperatively from donor and recipient, as well as 60 min after reperfusion. The mean ischemia time +/- SEM was 10 h 10 min +/- 53 min. Mean concentrations in University of Wisconsin preservation solution effluent were: interleukin-(IL-)1beta 154 +/- 77 pg/ml; IL-1 receptor antagonist (IL-1 ra) 1281 +/- 309 pg/ml; IL-6 412 +/- 90 pg/ml; and for tumor necrosis factor-(TNF-)alpha 74 +/- 21 pg/ml. Cytokine levels in the donors were lower than those detected in the effluent. All measured cytokines showed higher concentrations in the effluent compared to those of the recipient prior to the operation. With respect to a comparison of donor and recipient values, no correlation is evident. Likewise, the ischemic time does not correlate with effluent values. Further development of liver preservation concepts requires information about the state of the graft before reperfusion. Data on cytokine liberation may serve as a helpful tool for the further development of preservation concepts because they enable an estimation of cell activation during preservation.

Adenosine↗