Biomedical subjects

H Köhler

Publications and source records attributed to H Köhler.

At least 55 records · Page 3Linked to original sources

PubMed2001

Molecular aspects of T- and B-cell function in uremia.

Chronic renal failure is associated with severe alterations of the immune system. Infections are responsible for a large part of the mortality in hemodialysis patients, and vaccination is mostly ineffective. Global tests of the immune function show greatly diminished activation of T cells. However, the intrinsic function of T and B cells is normal when they are provided with normal signaling from antigen-presenting cells (APCs). Patients with chronic renal failure show a defective function of costimulation derived from APCs leading to impaired activation of effector lymphocytes. Two major components of immune deviation are relevant: reduced signaling caused by impaired expression of the costimulatory molecule B7-2 (CD86) on monocytes leads to low activation of helper T cells. This dysfunction is associated with uremia and may be improved by high-efficiency renal replacement therapy. The other component is inflammatory activation of APCs mainly due to the hemodialysis procedure. Inflammation, characterized by overproduction of cytokines such as interleukin-1beta (IL-1beta) or IL-6, correlates with low effector activation. Furthermore, inflammatory cytokines such as IL-12 deviate the functional pattern of T-cell activation toward Th1 differentiation, thus leading to an additional reduction of Th2- and B-cell function. The individual severity of inflammatory alterations is partially controlled by the negatively regulating cytokine IL-10, which, on a genetic basis, can be up-regulated to a different extent in individual patients. Therapeutic interventions to improve immune dysfunction include the enhancement of dialysis efficiency and the reduction of inflammatory alterations by the use of highly biocompatible dialyzers.

Antigen-Presenting Cells↗

PubMed2001

Hepatotoxic substance(s) removed by high-flux membranes enhances the positive acute phase response.

BACKGROUND: Acute phase proteins (APPs) are enhanced in end-stage renal disease patients (ESRD) requiring dialysis treatment. They are involved in a variety of pathologic processes like muscle proteolysis, cachexia, regulation of appetite, and atherosclerosis. They are predictive for mortality. APPs are not only makers but also active substances. They are mainly produced in liver cells and are primarily, but not exclusively, regulated by proinflammatory cytokines. To what extent hepatic APPs are influenced by uremic toxins is still unclear. Therefore, we investigated the effects of different ultrafiltrates (UFs) on the synthesis of alpha1-acid glycoprotein (AGP) in HepG2 cells. METHODS: A cross-sectional as well as a crossover study with high-/low-flux membranes was conducted to investigate the impact of UFs on bioactivity of liver cell cultures. Metabolic activity (MTT test), cytotoxicity (lactate dehydrogenase release), and the positive APP AGP were measured in HepG2 cells. RESULTS: Cultured hepatocytes treated with UFs from high-flux membranes exhibited a higher cytotoxicity (18.6 +/- 0.3% high-flux vs. 13.9 +/- 0.2% low-flux, P < 0.001) and a lower metabolic activity (29.3% high-flux vs. 50.3% low-flux, P < 0.001) in comparison with low-flux UFs. In addition, enhanced APP secretion could be observed under costimulatory conditions (high-flux 5.0 +/- 0.7 vs. low-flux 3.1 +/- 0.6 ng/microg protein, P < 0.05). The effects of high- and low-flux UFs were strongly expressed at the beginning and were still significantly different after 120 minutes of hemodialysis (HD) treatment. The crossover experiments confirmed that UFs collected during high-flux HD had a higher capacity to stimulate AGP synthesis in liver cells. CONCLUSION: The effects of UFs from dialysis patients demonstrate that hepatotoxic substances can be removed by dialysis. Stimulating the acute phase response UF collected during high-flux HD had a higher impact on liver cells in comparison with low-flux UF. These substances are putative cofactors involved in cytokine regulation.

Acute-Phase Reaction↗

PubMed2001

Pain management in children: assessment and documentation in burn units.

Burns are considered to be among the most painful types of trauma. Especially the pain of children is often unsatisfactorily treated. This study investigates the assessment and documentation of pain by physicians and nurses in children suffering from burns. Pain management was considered sufficient in 80% of ventilated patients and in 60% of non-ventilated patients. The minority of the staff regarded pain management as sufficient during dressing changes after the acute phase and during nursing care. Thirty-eight per cent of the physicians and 58% of the nurses documented the pain. Standardized documentation was used by fewer than 20% of the staff. Pain documentation was not considered relevant for further therapy by 48% of the physicians. More than half of all participants believed that an improvement of the pain therapy performed in their hospital was necessary. Standardized documentation, an algorithm for the application of analgesics, and more training in pain management were desired by many staff members.

Burn Units↗

PubMed2001

Strong depletion of CD14(+)CD16(+) monocytes during haemodialysis treatment.

BACKGROUND: The immune defect in haemodialysis (HD) patients is associated with a monocytic dysfunction, including an increased production of proinflammatory cytokines. Monocytes fall into subpopulations comprising CD14(++)CD16(-) and CD14(+)CD16(+) cells. Circulating numbers of the latter can rapidly increase during infectious episodes and inflammation. METHODS: We determined the amount of CD14(+)CD16(+) monocytes in HD patients and characterized their fate during HD treatment. In 34 HD patients and 17 healthy controls, the distinct cell populations were determined by differential blood counts and flow cytometry. Cells from 14 HD patients were analysed at the start, 10, 30 and 120 min thereafter, and at the end of HD treatment. RESULTS: Before HD, patients show a monocytosis with a strongly increased CD14(+)CD16(+) subpopulation. Early during HD treatment, circulating leukocyte numbers decrease, with monocytes being most profoundly influenced. Interestingly, among them, sequestration is most pronounced in the CD14(+) CD16(+) subpopulation. After 30 min, approximately 83+/-9% of CD14(+)CD16(+) cells are removed from circulation. This sequestration does not differ between patients treated with polyamide or haemophan membranes. The sequestration is a short-lived temporary effect and cell numbers are replenished within 120 min of treatment for the entire monocyte population. Beyond that time point, cellular activation by the dialyser membrane becomes visible. Reappearence kinetics of CD14(+)CD16(+) monocytes is slower; however, initial numbers are reached by the end of treatment. CONCLUSION: Haemodiaysis leads to temporary removal of monocytes from the bloodstream followed by the reappearance of activated cells. This might contribute to the state of chronic microinflammation, which is reflected by high levels of CD14(+)CD16(+) monocytes.

Antigens, CD↗

PubMed2001

Effect of Clostridium perfringens epsilon toxin on MDCK cells.

Epsilon toxin is one of the major lethal toxins produced by Clostridium perfringens type D and B. It is responsible for a rapidly fatal disease in sheep and other farm animals. Many facts have been published about the physical properties and the biological activities of the toxin, but the molecular mechanism of the action inside the cells remains unclear. We have found that the C. perfringens epsilon toxin caused a significant decrease of the cell numbers and a significant enlargement of the mean cell volume of MDCK cells. The flow cytometric analysis of DNA content revealed the elongation of the S phase and to a smaller extent of the G2+M phase of toxin-treated MDCK cells in comparison to untreated MDCK cells. The results of ultrastructural studies showed that the mitosis is disturbed and blocked at a very early stage, and confirmed the toxin influence on the cell cycle of MDCK cells.

Animals↗

PubMed2001

Superoxide anion generation in human milk macrophages: opsonin-dependent versus opsonin-independent stimulation compared with blood monocytes.

Macrophages are believed to play an important role within the immunoprotective effects of human breast milk. It was the purpose of this study to evaluate the capability of human milk macrophages (MMPhi) to generate superoxide anions (O2(-)) in comparison with peripheral blood monocytes (BMo) after stimulation with opsonized and unopsonized zymosan. Potential inhibitors of attachment and phagocytosis such as mannose and cytochalasin B were used. Expression of the mannose receptor on MMPhi was demonstrated by staining with MAb. BMo generated more O2(-) than MMPhi (417 +/- 79 versus 216 +/- 15 nmol O2(-)/mg protein, p < 0.05) after stimulation with opsonized zymosan. When unopsonized zymosan was used as a serum-independent stimulus, BMo generated slightly less O2(-) in comparison with MMPhi (150 +/- 34 versus 176 +/- 18 nmol O2(-)/mg protein, p < 0.05). These findings imply a higher proportion of opsonin-independent phagocytosis in MMPhi than in BMo (82 versus 36 %). Preincubation with mannose resulted in a significantly higher reduction of O2(-) generation in MMPhi compared with BMo stimulated with opsonized zymosan, whereas no difference was found when unopsonized zymosan was used. After addition of cytochalasin B, equal inhibition of O2(-) generation was observed regardless of the cell type or stimulus used. Thus, MMPhi are stimulated to a greater extent by serum-independent mechanisms than BMo. As opsonins like complement or IgG are rare in the colostrum and the neonatal intestinal environment, such a differentiation toward serum-independent phagocytic abilities could play an important role for protective functions of human MMPhi. Possible involvement of the mannose receptor and the beta-glucan receptor in this specialization are discussed.

Cells, Cultured↗

PubMed2000

Rapid whole blood analysis of virus-specific CD4 and CD8 T cell responses in persistent HIV infection.

OBJECTIVES: Upon HIV infection, strong antiviral cytotoxic and helper T cell responses are generated. They are considered to be an important component in the control of HIV viral load. A simple and rapid whole blood assay was established to quantify and simultaneously characterize HIV-reactive CD4 and CD8 cells. The assay was applied to evaluate the effect of antiretroviral therapy on HIV-specific T cell responses. METHODS: Whole blood of 33 HIV-infected individuals was specifically stimulated by HIV-1 Pr55gag, and activation-induced intracellular cytokine expression in CD4 and CD8 T cells was analysed by flow cytometry. RESULTS: HIV-1-specific CD8 and CD4 T cells can be quantified simultaneously. As specific antigen, HIV-1 Pr55gag virus-like particles were superior to soluble protein, especially for the activation of CD8 T cells. In untreated individuals, a high frequency of HIV-specific T cells was observed. The frequency of CD8 T cells was consistently higher than the respective CD4 T cell response, thus demonstrating a dominance in CD8 T cell expansion in persistent HIV infection. Patients on antiretroviral therapy showed a significant reduction in HIV-specific CD4 and, even more strikingly, CD8 T cells. CONCLUSION: The whole blood assay provides a rapid estimate of the total antiviral T cell resources, and is highly suited for a clinical setting. It may thus have widespread applications for the evaluation of vaccination strategies and immunotherapy. Because antiretroviral therapy significantly reduces both HIV-specific cytotoxic and helper T cell responses, future therapeutic strategies should aim at improving cellular antiviral immunity.

Adult↗

PubMed2000

Antibody reactions after aerogenous or subcutaneous immunization of pigs with Pasteurella multocida antigens.

Depending upon the antigens used and the initial titres, subcutaneous immunization of weaner pigs by means of a temperature-sensitive mutant of live Pasteurella multocida (serovar A), resulted in a significant rise of the level of specific IgG antibody already present in blood serum, but not in lung lavage fluid, and a specific stimulation of lung clearance as compared to non-immunized controls. Aerogenous immunization of a total of 108 animals in 18 experiments did not influence serum antibody titres but produced a significant rise in lung antibodies and P. multocida clearance as compared to an identical number of controls. In all 12 immunization experiments using the live mutant, increased specific IgA antibodies and in seven out of 10 experiments, elevated IgG antibodies were measured. Only aerogenous immunization was found to be capable of reducing the severity of pneumonia induced by intrabronchial infection.

Aerosols↗

PubMed2000

Glycyl-glutamine improves in vitro lymphocyte proliferation in AIDS patients.

BACKGROUND: Glutamine (Gln) is a major nutrient for rapidly proliferating cells. Unlike glutamine itself, the dipeptide glycyl-glutamine as a source for Gln is stable in aqueous solutions ex vivo. In order to evaluate the possible therapeutic role of glycyl-glutamine on lymphocyte proliferation we investigated its influence on lymphocytes of AIDS patients and healthy controls under stimulation with different mitogens. MATERIAL AND METHODS: Lymphocytes were collected from 11 adult patients suffering from AIDS according to the CDC definition and from 7 adult healthy donors. Glutamine (Gln) and glycyl-glutamine (GlyGln), respectively, were added to cell cultures at concentrations between 0 and 1.0 mmol/l. ConA or SAC served as T or B cell mitogens, respectively. Plasma amino acid levels were determined. RESULTS: Proliferation upon ConA-stimulation with GlyGln-supplementation was similar to Gln-supplementation and peaked dose dependently at 1.0 mmol/l. When SAC was used Gln seemed slightly superior to GlyGln with a peak at 0. 4 mmol/l but the results did not reach the level of statistical significance. An identical response pattern was demonstrated in HIV-patients, however at lower absolute proliferation rates. Normal values could not be restored. Overall, the use of either source of glutamine in equimolar concentrations did not result in major differences of proliferation. Glutamine and glycin plasma levels did not differ between HIV patients and controls. CONCLUSION: GlyGln can be used as a substitute for Gln with regard to lymphocyte proliferation. Lymphocytes from AIDS patients show, as controls do, an enhanced proliferation under supplementation either glutamine source. Supplementation of GlyGln might enhance lymphocyte proliferation and thus improve immunity.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Opsonophagocytosis versus lectinophagocytosis in human milk macrophages.

Some important immunoprotective effects of human breast milk have been attributed to the presence of macrophages. We investigated the generation of superoxide anion (O2-) by monocytes and human milk macrophages after stimulation with opsonized and unopsonized zymosan in the absence and presence of mannose as an inhibitor to investigate lectinophagocytic and opsonophagocytic properties. Peripheral blood monocytes generated more O2- than human milk macrophages (417,4 + 79,1 nmol O2-/mg protein vs. 216,1 +/-15,1 nmol O2-/mg protein, p<0,05) after stimulation with opsonized zymosan. When unopsonized zymosan was used as a serum-independent stimulus monocytes generated slightly less O2- in comparison to human milk macrophages (150,8 +/- 34,5 nmol/mg protein vs. 176,1 +/- 18 nmol O2-/mg protein, p<0,05). These findings demonstrate that the proportion of opsonin-independent phagocytosis in human milk macrophages is higher than in monocytes (82% vs. 36%). When mannose was used as an inhibitor a significantly higher reduction of O2- generation occurred in human milk macrophages compared to monocytes stimulated with opsonized zymosan, whereas no difference was found when unopsonized zymosan was used. These results indicate that human milk macrophages are stimulated to a greater extent by opsonin-independent mechanisms than blood borne monocytes. As the colostrum and the intestinal environment of the neonate offers only a little amount of opsonins like complement and immunoglobulin G, such a differentiation to lectinophagocytic properties could bear a great advantage for protective functions of human milk macrophages.

Adjuvants, Immunologic↗

PubMed2000

[Strategies for the use of amino acids. Catabolism and retention].

Extensive Catabolism is a hallmark of patients with acute renal failure (ARF) complicating critical illnesses. Catabolism is due to dysregulation of protein metabolism as well as a consequence of diminished renal excretion and renal replacement therapy (RRT). Inadequate nutritional support predisposes patients to malnutrition and increased mortality risk. Since the catabolic rate varies widely in ARF patients and can not be predicted by clinical parameters, direct quantification of the protein catabolic rate should be performed regularly. The urea nitrogen appearance rate (UNA) is a valid and reproducible estimate of nitrogen balance in critically ill patients undergoing continuous RRT. Amino acid losses up to 50 g/day and protein losses up to 15 g/day occur during continuous RRT and need to be compensated for. In order to achieve neutral or positive nitrogen balance a nutritional regimen providing 1.5-2.0 g protein/kg/day and 25-35 kcal/kg/day may be required. Since glutamine losses during continuous RRT may exceed 4 g/day, glutamine supplementation (0.3-0.5 g/kg/day) appears to be recommendable.

Acute Kidney Injury↗

PubMed2000

[Myelodysplastic syndromes (MDS). Aspects of hematopathologic diagnosis].

Myelodysplastic syndromes (MDS) are a heterogenous group of clonal stem cell disorders which generally occur in older adults but may also affect children. Primary MDS should be distinguished from secondary MDS associated with antineoplastic or immunosuppressive therapy (t-MDS), exposure to toxic compounds, or genetic disorders. The establishment of a neoplastic clone is reflected by dysplastic features and impaired function which may affect all three hematopoietic cell lineages. The ineffective hematopoiesis which causes bone marrow failure is accompanied by peripheral blood cytopenia and is considered to result from increased apoptosis, at least in the less advanced MDS stages. The elucidation of the molecular pathogenesis of MDS has provided evidence that chromosomal abnormalities are present in about 50% of patients with primary MDS. They include numerical aberrations such as monosomy 5 or 7, trisomy 8, loss of the Y-chromosome and structural abnormalities such as deletion of the long arm of chromosome 5 (5q-syndrome), 7, or 8. Based on the percentage of blasts (<5%, 5-20%, 20-30%) and the presence of >15% ringed sideroblasts for marrows with <5% blasts, the French-American-British (FAB) classifies MDS into 4 morphologic categories: refractory anemia (RA), refractory anemia with excess of blasts (RAEB), refractory anemia with excess of blasts in transformation (RAEB-t), and refractory anemia with ringed sideroblasts. The fifth morphologic type is chronic myelomonocytic leukemia characterized by peripheral blood monocytosis (>1x10(9)/l). However, a modification of this classification will be proposed by the World Health Organization, with the intention of lowering the threshold for the diagnosis of AML from 30% to 20% blast cells. In patients presenting with cytopenias suggesting impaired hematopoiesis, the initial diagnosis depends mainly on the cytological evaluation of bone marrow and blood smears and the histological findings of trephine bone marrow biopsy. In a retrospective analysis we evaluated the occurrence of the distinct FAB-categories as percentage of the total number of MDS cases diagnosed at the Institute of Pathology of the University of Freiburg. A total of 63% fullfilled the criteria of RA/RARS, 17% of RAEB, 14% of RAEB-t, and 6% of CMML. A fibrotic variant of MDS was observed in 7.67% of all cases, ranging from 2.34% in RA up to 15. 42-15.84% in the categories which did not show significant differences with regard to myelofibrosis. The histologic evaluation of a trephine bone marrow biopsy is of critical importance for the evaluation of fibrotic or hypocellular MDS since these patterns are not reflected by the cytological examination. The combined cytological and histological diagnosis of bone marrow and peripheral blood is a reliable tool for the initial diagnosis of MDS. In addition, cytogenetic and molecular analysis should be performed. Presently, the risk of leukemic transformation is evaluated using the International Prognostic Scoring System for MDS, which is the sum of the scores of bone marrow blasts, karyotypes and cytopenia. In the context of clinical trials therapeutic modalities should be considerd according to the age and the general performance state and the prognostic scores of individual patients.

Adult↗

PubMed2000

Lymphocyte proliferation is possible with low concentrations of glycyl-glutamine.

The positive effect of glutamine on lymphocyte proliferation has previously been described. Its dipeptide glycyl-glutamine (GlyGln) is more stable than pure glutamine in aqueous solutions. The aim of our study was to investigate the relationship between lymphocyte proliferation and varying concentrations of glycyl-glutamine in vitro. Isolated human lymphocytes were stimulated with the mitogens phytohaemagglutinin (PHA), Concanavalin A (ConA), pokeweed mitogen (PWM), and Staphylococcus aureus (SAC). Glycyl-glutamine was added to yield final concentrations of 0-2 mmol/l. Overall, minimal concentrations of 0.01 mmol/l glycyl-glutamine were sufficient to enhance lymphocyte proliferation over baseline (glutamine-free) levels. No difference was found between concentrations in the "physiological" range of 0.4 mmol/l and very low concentrations (0.04-0.1 mmol/l) with SAC, ConA and PWM. Increasing the concentration beyond 0.4 mmol/l (up to 2.0 mmol/l) offered further gain with PHA-stimulation only. Lymphocyte proliferation under in vitro polyclonal stimulation is maintained even at very low concentrations of glycyl-glutamine. Raising the concentration above the equivalent of physiological levels does not seem to provide further benefit.

Adult↗

PubMed2000

Stability of carbohydrate deficient transferrin (CDT) in stored blood samples.

The alcoholism marker CDT was determined on 257 blood samples 1-2 days after the blood samples were taken and again after storage for 7 months at +4 degrees C. The differences between the pairs of CDT values were so large that the determination of CDT after long term storage of the blood sample has no evidential value.

Alcoholism↗

PubMed2000

ROC analysis of alcoholism markers--100% specificity.

A combination of 4 so-called markers of alcoholism, i.e. methanol, acetone + 2-propanol, gamma-glutamyltransferase and carbohydrate deficient transferrin, was investigated in 341 blood samples from alcoholics and non-alcoholics. From the history of alcohol consumption, four defined subgroups were formed: non-alcoholics divided into (A) 33 persons with no ethanol consumption during the past year and (B) 60 persons with daily consumption less than 40 g ethanol. Alcoholics were divided into (C) 177 persons with no ethanol at the time of admission/first blood sampling (withdrawal therapy) and (D) 71 persons with positive ethanol levels on admission/first blood sampling. All markers showed different extents of overlap between the collectives of alcoholics and non-alcoholics. By logistic regression, a formula was developed combining these markers with different mathematical weights. Thus an "Alc-Index" could be calculated for each individual. The ROC curve connecting all individual values gives an ideal form with 100% specificity and nearly 93% sensitivity. The threshold between the collectives of alcoholics and non-alcoholics was defined by the Alc-Index value 1.7. This was associated with no false positives among the non-alcoholics while nearly 93% of the alcoholics exceeded this index. The ROC-based calculation of the Alc-Index thus seems to be the most effective method for the diagnosis of alcoholism.

1-Propanol↗

PubMed2000

Biomaterial-induced sarcoma: A novel model to study preneoplastic change.

In the study of carcinogenesis most interest has focused on carcinomas, as they represent the majority of human cancers. The recognition of the adenoma-carcinoma sequence both in humans and in animal experimental models has given the field of basic oncology the opportunity to elucidate individual mechanisms in the multistep development of carcinoma. The relative scarcity of human sarcomas coupled with the lack of adequate animal models has hampered understanding of the molecular genetic steps involved. We present an experimental model in the rat in which a high incidence of malignant mesenchymal tumors arise around a subcutaneously implanted biomaterial. Nine commercially available biomaterials were implanted in a total of 490 rats of the Fischer strain for 2 years. On average, macroscopic tumors were found in 25.8% of implantation sites over a period from 26 to 110 weeks after implantation. The most frequent tumors were malignant fibrous histiocytomas and pleomorphic sarcomas, although fibrosarcomas, leiomyosarcomas, and angiosarcomas readily developed, the latter especially around polyurethane implants. Of particular interest are the results of a detailed histological study of the capsules around the implanted biomaterials without tumors. Here a spectrum of change from focal proliferative lesions through preneoplastic proliferation to incipient sarcoma could be observed. A parallel immunohistochemical study of peri-implant capsules showed that proliferating cell nuclear antigen was of particular help in identifying these atypical proliferative lesions. To our knowledge this is the first description of a sarcoma model in which preneoplastic lesions can be readily identified and also reproducibly induced. This model provides the molecular biologist with defined stages in the development of mesenchymal malignancy, with which the multistage tumorigenesis hypothesis can be tested, analogous to the well-known adenoma-carcinoma sequence.

Animals↗

PubMed2000

Initiation of hemodialysis treatment leads to improvement of T-cell activation in patients with end-stage renal disease.

Patients with chronic renal failure show an immunodeficiency characterized by frequent infectious complications and a low response to vaccinations. This is paralleled in vitro by a low T-cell proliferation on mitogenic stimuli because of an impaired costimulation by accessory cells. Furthermore, alterations of the cytokine profile are correlated with impaired immune function. The immune system is influenced by both uremia and renal replacement therapy. To evaluate the influence of hemodialysis on immune parameters, we studied patients before and after the initiation of chronic hemodialysis therapy. Fourteen patients with end-stage renal failure were tested before dialysis initiation and during the first 6 weeks of hemodialysis treatment. We determined the in vitro T-cell proliferation, as well as plasma levels of interleukin-6 (IL-6) and the release of IL-6 and IL-10 into culture supernatant poststimulation with lipopolysaccharide. After 6 weeks of intermittent hemodialysis, in vitro T-cell proliferation on stimulation improved significantly (stimulation index, 21.6 +/- 18.5 versus 58.1 +/- 45.5; P < 0.01). This improvement occurred regardless of whether synthetic dialyzers or cellulosic membranes were used for the initiation of dialysis. Plasma IL-6 levels, as well as IL-6 and IL-10 secretion, did not change during the study period. In patients with end-stage renal disease, the initiation of hemodialysis led to a significant improvement of in vitro T-cell proliferation. This effect may have a role for an improvement of immune function in vivo. The expected normalization of IL-6 and IL-10 production may be masked by cytokine induction through hemodialysis membranes.

Humans↗

PubMed2000

Prospective crossover trial of the influence of vitamin E-coated dialyzer membranes on T-cell activation and cytokine induction.

Cytokine induction by dialyzer membranes has been related to several acute and chronic side effects of hemodialysis treatment, among them being immune dysfunction and progressive atherosclerosis. Surface modification of cuprophane dialyzers with the antioxidant vitamin E is a new approach to enhance biocompatibility and improve cytokine levels, as well as immune function. Twenty-one patients undergoing treatment with hemophane (HE) dialyzers were enrolled onto a crossover study with a vitamin E-coated (VE) dialyzer or a synthetic polyamide (PA) dialyzer. In vitro assays of lymphocyte activation and measurements of cytokine induction were performed to evaluate biocompatibility. Four weeks of treatment with either VE or PA dialyzers enhanced in vitro proliferation of peripheral blood leukocytes in comparison to treatment with HE membranes used before study entry. Enhancement of lymphocyte function was independent of dialysis efficiency, which was kept constant during the study. In the interdialytic interval, preactivation of monocytes for the production of interleukin-6 (IL-6) did not differ between VE or PA dialysis. In contrast, the VE membrane reduced acute production of IL-6 during a dialysis treatment, whereas the PA membrane did not. Unlike IL-6, the regulatory cytokine IL-10 is not inhibited by either membrane. This is important because IL-10 is believed to have a beneficial effect on immune function in dialysis patients. The VE membrane, despite being based on a cuprophane backbone, is similar to the highly biocompatible PA dialyzer in terms of its effect on lymphocyte function, whereas it exerts an additional suppressive effect on the overproduction of proinflammatory cytokines.

Aged↗