Polymethylmethacrylate Membrane Research Articles

Effectiveness of Continuous Hemodiafiltration Using a Polymethylmethacrylate Membrane Hemofilter After Polymyxin B-Immobilized Fiber Column Therapy of Septic Shock

Septic shock is a condition associated with diffuse coagulopathy and multiple organ failure, and frequently ends in death. Direct hemoperfusion using a polymyxin B-immobilized fiber column (DHP-PMX) was first developed in Japan in 1994 and has since been used for the treatment of septic shock. On the other hand, the effectiveness of continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA- CHDF) for critically ill patients has also been reported. We treated 27 septic shock patients by DHP-PMX. The patients, except for the nine in whom CHDF was not performed after DHP-PMX, were divided into two groups: namely, a group in which PMMA-CHDF therapy was added after DHP-PMX (11 cases), and a group in which continuous hemodiafiltration using a polyacrylonitrile membrane hemofilter (PAN-CHDF) therapy was added after DHP-PMX (7 cases). The outcomes in the two groups were compared. The average Acute Physiology and Chronic Health Evaluation (APACHE) II score and the average sepsis-related organ failure assessment (SOFA) score were not significantly different between the two groups. The PMMA-CHDF group showed significantly better outcomes, with significant improvements of the serum PAI-1, protein C, IL-6 and N-arachidonoylethanolamine (AEA) levels. We conclude that PMMA-CHDF may be more effective than PAN-CHDF in the management of septic shock.

Effectiveness of continuous venovenous hemodiafiltration using a polymethylmethacrylate membrane hemofilter in septic shock patients

Septic shock is a condition associated with diffuse coagulopathy and multiple organ failure, and frequently ends in death. The effectiveness of continuous venovenous hemodiafiltration (CVVHDF) using a polymethylmethacrylate membrane hemofilter (PMMA) for critically ill patients has also been reported.

Clinical significance of protein adsorbable membranes--Long-term clinical effects and analysis using a proteomic technique

Polymethylmethacrylate (PMMA) membranes were first developed in Japan in 1977. Over its 30-year history, use of PMMA has given rise to a new generation of dialysers and continues to evolve. In long-term observation of patients treated with PMMA membranes (BK series), it has been found that serum beta2-microglobulin is maintained at a significantly lower level than in haemodialysis (HD) patients undergoing treatment with conventional cellulosic membranes. Regarding long-term side effects, radiolucent bone cysts (RBC) and carpal tunnel syndrome (CTS) have developed in relatively few patients undergoing HD with PMMA membranes. The profiles of various proteins in the blood of HD patients differ from those in normal subjects. PMMA membranes remove a wide variety of solutes not only via permeation, but also adsorption. Numerous reports have noted that pruritus can be ameliorated with the use of slightly anionic PMMA membranes (BG series). We have been performing proteomic analysis of plasma from HD patients with pruritus. We have confirmed that slightly anionic PMMA membranes can adsorb components with a molecular weight of 160,000 Da, which have stimulatory effect on mast cells from pruritus.

Platelet activation through interaction with hemodialysis membranes induces neutrophils to produce reactive oxygen species

The intradialytic activation of leukocytes is one of the major causes of hemodialysis-associated complications. During hemodialysis, the formation of microaggregates consisting of platelets and neutrophils has been observed to accompany the production of reactive oxygen species (ROS) by leukocytes. In this study, we investigated the interaction of platelets and neutrophils with hemodialysis membranes in vitro to elucidate the mechanism underlying microaggregate formation and its relevance to leukocyte activation. The production of ROS in neutrophils was induced by the coincubation of neutrophils with polysulfone (PS) membranes, and was increased when platelets were present in the neutrophil suspension. Neutrophils that were incubated with polymethylmethacrylate (PMMA) membranes in the presence of platelets also produced significant levels of ROS, suggesting that the presence of platelets augmented ROS production in neutrophils. Platelets adhered more firmly to hydrophobic membranes such as PS and PMMA membranes than to hydrophilic membranes, such as those composed of regenerated cellulose (RC) or ethylene vinylalcohol copolymer (EVAL). The adhesion of platelets to dialysis membranes composed of different materials was correlated with those membranes' ability to induce platelet activation as assessed by the cell surface expression of P-selectin. Moreover, coincubation of neutrophils with platelets that had been treated with hydrophobic membranes induced a higher level of superoxide anion relative to those treated with hydrophilic membranes in association with the P-selectin-mediated microaggregate formation. These results suggest that platelets activated through interaction with hemodialysis membranes stimulate neutrophils to produce ROS via P-selectin-mediated adhesion, and that this property of adhesion to platelets is critical for the biocompatibility of hemodialysis membranes.

Glucose oxidase immobilization on a novel cellulose acetate–polymethylmethacrylate membrane

Glucose oxidase (GOD) was immobilized on cellulose acetate–polymethylmethacrylate (CA–PMMA) membrane. The immobilized GOD showed better performance as compared to the free enzyme in terms of thermal stability retaining 46% of the original activity at 70 °C where the original activity corresponded to that obtained at 20 °C. FT-IR and SEM were employed to study the membrane morphology and structure after treatment at 70 °C. The pH profile of the immobilized and the free enzyme was found to be similar. A 2.4-fold increase in K m value was observed after immobilization whereas V max value was lower for the immobilized GOD. Immobilized glucose oxidase showed improved operational stability by maintaining 33% of the initial activity after 35 cycles of repeated use and was found to retain 94% of activity after 1 month storage period. Improved resistance against urea denaturation was achieved and the immobilized glucose oxidase retained 50% of the activity without urea in the presence of 5 M urea whereas free enzyme retained only 8% activity.

Effect of tacticity of PMMA on gas transport through membranes: MD and MC simulation studies

The effects of tacticity of poly methyl methacrylate (PMMA) on the morphology and size distribution of free volume and gas molecules transport through PMMA matrix were conducted by molecular simulation techniques. How the spatial structure of PMMA affects the glass transient temperature T g of stereoregular PMMA membranes and the solution and diffusion mechanisms in the stereoregular PMMA membranes were conducted by molecular simulation techniques and were compared with experimental data. The polymer chains conformation, gas diffusion mechanism, the time course of the accessible free volume, free volume size distribution, free volume morphology and glass transient temperature, in the various stereoregular PMMA were obtained by a molecular dynamics simulation technique, while the gas solubility in different stereoregular PMMA was calculated by a Monte Carlo technique. A comprehensive comparison of the physical and transport properties of the stereoregular PMMA membranes between simulated and experimental results are provided based on a microscopic interpretation of chain flexibility, free volume morphology and size distribution of free volume in the stereoregular PMMA membranes and gas molecule transport mechanisms through the stereoregular PMMA membranes.

Management of Intra‐abdominal Hypertension in Patients With Severe Acute Pancreatitis With Continuous Hemodiafiltration Using a Polymethyl Methacrylate Membrane Hemofilter

To evaluate, with a prospective observational study, whether continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter (PMMA-CHDF) is effective for prevention and treatment of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) on patients with severe acute pancreatitis (SAP). The study was carried out in the general intensive care unit (ICU) of a university hospital. Seventeen consecutive patients with SAP were treated in the intensive care unit and underwent PMMA-CHDF whether or not they had renal failure. Blood level of interleukin (IL)-6, as an indicator of cytokine network activation, and intra-abdominal pressure (IAP) were measured daily to investigate their time-course of changes and the correlation between the two. The blood level of IL-6 was high at 1350+/-1540 pg/mL on admission to the ICU. However, it significantly decreased to 679+/-594 pg/mL 24 h after initiation of PMMA-CHDF (P<0.05), and thereafter decreased rapidly. Mean intra-abdominal pressure (IAP) on admission was high, at 14.6+/-5.3 mm Hg, with an IAP of 20 mm Hg or over in 2 of 17 patients, showing that they had already developed IAH. The IAP was significantly lower (P<0.05) 24 h after initiation of PMMA-CHDF, and subsequently decreased. There was a significant positive correlation between blood level of IL-6 and IAP, suggesting that PMMA-CHDF improved vascular permeability through elimination of cytokines, and that it thereby decreased interstitial edema to lower IAP. Sixteen of the 17 patients were discharged from the hospital in remission from SAP without development of complications. Continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter appears to be effective for prevention and treatment of IAH in patients with SAP through the removal of causative cytokines of hyperpermeability.

Molecular dynamics simulation study of the effect of PMMA tacticity on free volume morphology in membranes

The effect of the tacticity of poly methyl methacrylate (PMMA) on the morphology of free volume in PMMA membranes was studied by using a molecular dynamics simulation technique. The chain flexibility, chain interaction, end-to-end distance of a chain and the time course of the free volume variation in the various stereo-regular PMMA, were obtained by an MD simulation technique. Simulation results depict that the construction of distinct tacticity has a significant influence on the flexibility of a molecular chain and the morphology of free volume in the syndiotactic (s-) and isotactic (i-) PMMA oligomers. MD calculation of the dynamic microstructure of a PMMA matrix shows that the s-PMMA membrane gives less flexibility in the backbone and a longer end-to-end distance than in the i-PMMA membrane. The less flexibility and longer end-to-end distance in the s-PMMA matrix causes the shapes and sizes of s-PMMA free volume to be longer and larger than those in an i-PMMA membrane. Furthermore, by adopting conformation energy minimization and molecular dynamics simulation techniques, various tacticity models of PMMA were constructed and their effect on the size of accessible free volume and free volume morphology was analyzed. Finally, the adsorbed gas on the surface free volume in s-PMMA was also compared with i-PMMA membrane.

Pharmacokinetics of Midazolam in Critically Ill Patients Receiving Continuous Hemodiafiltration using a Polymethyl Methacrylate and/or Polysulfone Membrane

The objectives of this study were to evaluate the risk of the accumulation of midazolam and its active metabolites in critically ill patients in an intensive care unit (ICU) being treated by continuous hemodiafiltration (CHDF) using a polymethyl methacrylate (PMMA) and/or a polysulfone (PS) membrane and the influence of CHDF on the pharmacokinetics of midazolam in these patients. The serum and ultrafiltration liquid concentrations of midazolam and its active metabolites were measured by high-performance liquid chromatography to study the pharmacokinetics of midazolam and its active metabolites in seven patients with renal failure who were being treated by CHDF using a PMMA and/or a PS membrane. There was no progressive accumulation of midazolam or 1-hydroxymidazolam, though high levels of 1-hydroxymidazolam glucuronide were noted. The extraction rates for these 3 substances by CHDF using a PMMA and a PS membrane were 1.3%, 3.0% and 13.4%, and 5.0%, 4.8 % and 74.4%, respectively. A positive correlation was observed between the 1-hydroxymidazolam glucuronide concentration and serum creatinine concentration for CHDF using the PMMA membrane (r2=0.8223), while there was no correlation between these concentrations when the PS membrane was used (r2=0.0361). These results show that CHDF using a PMMA membrane did not affect the elimination of 1-hydroxymidazolam glucuronide but it was affected when the PS membrane was used. The risk of accumulation of 1-hydroxymidazolam glucuronide and the need for prolonged sedation should be therefore be taken into account in drug dose adjustment for patients undergoing CHDF.

Control of intra-abdominal pressure in severe acute pancreatitis with continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter and colloid fluid therapy

Control of intra-abdominal pressure in severe acute pancreatitis with continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter and colloid fluid therapy

Soft X-ray imaging of living cells in water: flash contact soft X-ray microscope

Flash contact soft X-ray microscopy (FCSXRM) is an imaging technology for observing living cells in aqueous conditions with a spatial resolution of several tens of nm. The principle of soft X-ray imaging for living cells is carbon imaging, which provides us with a carbon-density-distribution map of the specimens. Carbon and oxygen have absorption edges in the soft X-ray wavelength range at 4.4 and 2.3 nm, respectively. Between these edges, the photoabsorption cross-section of carbon is about 10 times greater than that of oxygen. Thus, one can obtain soft X-ray images of living cells in water using this wavelength range. Laser-produced plasma is used as a flash X-ray source. A table-top FCSXRM, named FCSXRM ETL Mark 3, was developed in 1996 for convenient laboratory use of SXRM. The X-ray image of a specimen is recorded on a photoresist polymethyl methacrylate (PMMA) membrane supported on a silicon wafer. The X-ray image is then enlarged by an atomic force microscope (AFM). The practical resolution achieved by the system is about 40 nm, including the tip effect of the AFM. In this article, I discuss the possible roles of the FCSXRM for nanometer-scale imaging of living cells under physiological conditions.

Polymethylmethacrylate membrane for fluid encapsulation and release in microfluidic systems

A multipolymeric fabrication process using polymethlymethacrylate (PMMA) as a membrane layer was demonstrated for a robust dermal patch, called the bio-fluidic integrable transdermal (B–FIT) microsystem. B–FIT is a noninvasive microdevice, in the form of an adhesive patch, which samples biomolecules from interstitial fluids using controlled thermal ablation and encapsulated fluid that is released during biomolecule collection. Thus, a membrane material was needed that could encapsulate the fluid and easily liberate it, on demand, with minimal energy and compatibility with the fabrication process. PMMA was selected as the most promising membrane material for the B–FIT as against SU-8 since it had the required properties of low melting temperature (120–150 °C), good adhesion to pre-existing B–FIT materials (gold and SU-8), and could be easily spin-cast into thin uniform films. However, PMMA is not inert towards various solvents like acetone, photoresist developers, hence, a process was developed to protect PMMA from being attacked by the solvents used during the fabrication of the device. In this process, several strategies were employed such as crosslinking and application of thin protection layers on the PMMA. By exploring these fabrication strategies, PMMA was successfully patterned and the desired encapsulation and rupturing of the membrane was obtained.

Modulation of Polymorphonuclear Leukocyte Apoptosis in the Critically Ill by Removal of Cytokines with Continuous Hemodiafiltration

Delay of polymorphonuclear leukocyte (PMN) apoptosis caused by hypercytokinemia is considered to be a potential cause of tissue damage and resultant organ failure. We evaluated whether continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF), which can remove cytokines in the circulating blood, can modulate apoptosis in peripheral blood neutrophils and thereby reduce tissue damage and organ dysfunction in 25 critically ill patients. Following the completion of a 3-day PMMA-CHDF session, serum cytokine levels were significantly decreased and the percentage of apoptotic PMNs was significantly increased. A significant correlation was observed between the PMMA-CHDF-induced increase in the percentage of apoptotic PMNs and the degree of decrease in the serum interleukin-6 level. A significant correlation was also found between the increase in the percentage of apoptotic PMNs and improvement in sequential organ failure assessment score following PMMA-CHDF. These results suggest that PMMA-CHDF in critically ill patients with hypercytokinemia and concomitant delay in apoptosis of PMNs can alleviate the delay of PMN apoptosis through the removal of serum cytokines and thus may result in avoidance of organ dysfunction.

Effect of dialysis on serum/plasma levels of free immunoglobulin light chains in end-stage renal disease patients.

Free immunoglobulin light chains (FLCs) have previously been shown to be uraemic toxins. In this work we investigated the effect of haemodialysis and haemodiafiltration on the level of FLCs in serum/plasma of uraemic patients. Serum/plasma proteins were separated by non-reducing SDS-PAGE and transferred to a nitro-cellulose membrane. FLCs were detected by specific antibodies and an enhanced chemiluminescence detection system. The FLC concentrations were calculated. We studied 15 healthy subjects, 10 patients with chronic renal failure, 71 patients undergoing haemodialysis treatment and 33 patients treated with haemodiafiltration. Different membranes were compared: low- and high-flux polysulfone membranes, low- and high-flux cellulose triacetate membranes, high-flux polymethylmethacrylate and polyacrylonitrile membranes. Chronic renal failure patients showed elevated FLC concentrations as compared with controls. In haemodialysis or haemodiafiltration patients these values were even higher. This was mainly due to an increased concentration of FLC of the lambda-type. The treatment modality per se did not influence the FLC concentrations. Only haemodialysis or haemodiafiltration with the polymethylmethacrylate membrane lead to a significant reduction in FLC concentrations; however, these did not reach control levels. We did not observe differences in FLC levels between patients with different underlying diseases, nor did we find a correlation between age or the duration of the dialysis treatment and FLC concentrations. We found a positive correlation between FLC concentrations at the beginning of dialysis treatment and the amount of IgLCs removed during treatment. However, the average FLC level after treatment did not reach control values. Currently available haemodialysis or haemodiafiltration treatments are unable to normalize the elevated serum/plasma levels of FLCs in end-stage renal disease patients.

Influence of various hemodialysis membranes on the plasma (1→3)-β-D-glucan level

Recently, invasive fungal infections have increased significantly because of the growing number of immunocompromised hosts. The measurement of plasma (1-->3)-beta-D-glucan has been proposed as a useful diagnostic tool for deep mycosis. In this study, we analyzed the alteration of the plasma (1-->3)-beta-D-glucan concentration by using different kinds of hemodialysis (HD) membranes in end-stage renal disease (ESRD) patients and estimated its half-life. Twenty-seven patients with ESRD without known fungal infections (with a median age of 66 years old) were enrolled in this study. Cellulose triacetate (CTA) membrane, cellulose (Cu) membrane, and polymethyl methacrylate (PMMA) membrane were used in three consecutive initiations of HD and plasma (1-->3)-beta-D-glucan concentration was measured before and after each HD session. The level did not change between before and after HD when CTA and PMMA membranes were used. In contrast, the plasma (1-->3)-beta-D-glucan level increased greatly after HD using the Cu membrane (from 9.4 to 332 pg/mL in median). Hypothesizing that the plasma (1-->3)-beta-D-glucan level declines exponentially, its median half-life is estimated at 20 hours, which is not affected by hepatic or renal function. Because the plasma (1-->3)-beta-D-glucan level increases dramatically after HD using the Cu membrane, dialyzers with Cu membrane should be avoided for HD in patients with suspected deep mycosis. The measurement of plasma (1-->3)-beta-D-glucan is also useful for the patients with hepatic or renal failure.

Polymethylmethacrylate efficacy in reduction of renal itching in hemodialysis patients: crossover study and role of tumor necrosis factor-alpha.

Pruritus is one of the major unsolved problems for patients receiving regular hemodialysis. In this study, we conducted a 6 month prospective and crossover trial to investigate the effect of polymethylmethacrylate (PMMA) membrane for renal itching. We also examined the role of the tumor necrosis factor (TNF)-alpha system for pruritus in hemodialysis patients. We assessed the degree of skin itching and measured circulating levels of TNF-alpha and soluble TNF receptors (sTNFR-I, sTNFR-II) in 19 patients using hemodialysis, complicated by prolonged severe pruritus for 6 months. Serum sTNFR-I and II levels were significantly elevated in hemodialysis patients compared to normal subjects. Serum sTNFR-II levels were significantly and negatively correlated with serum albumin (r = -0.602, p = 0.007). A significant positive relationship was also found between sTNFR-I and erythropoietin dosage (r = 0.554, p = 0.016). However, no association was found between the degree of pruritus and circulating sTNFR-I and II values. Skin itching scale was significantly decreased from 2.7 +/- 0.2 to 2.1 +/- 0.3 following the use of PMMA membrane for 3 months (p < 0.05). In contrast, there was no change in itching scales during 3 months of conventional therapy (2.2 +/- 0.3 versus 2.2 +/- 0.3, p = NS). PMMA itself did not affect serum TNF-alpha and sTNFR values as well as conventional dialyzer membranes. These findings suggested that the PMMA dialyzer can improve renal itching not mediated through the modification of the TNF-alpha system.

Role of different dialysis membranes in the release of interleukin-6-soluble receptor in uremic patients

Interleukin-6 (IL-6) exerts its actions through a cell-surface receptor system that consists of two transmembrane subunits: the IL-6 binding glycoprotein gp 80 (IL-6R) and the signal-transducing component (gp 130). Soluble forms of the IL-6R (sIL-6R) are generated by shedding of the membrane-associated proteins. The sIL-6R binds the ligand IL-6 with comparable affinity as the membrane-associated IL-6R and enhances the actions of IL-6. Our aim was to evaluate the role of both uremia and different dialysis membranes on peripheral blood mononuclear cell (PBMC) release (either in absence or in presence of mitogen stimulation) and plasma levels of sIL-6R. Ten patients chronically dialyzed with cuprophan membranes (CU), eight patients on regular dialysis treatment with polymethylmethacrylate (PMMA) membranes, 11 uremic nondialyzed patients (UR), and 12 healthy subjects (CON) were included in the study. PBMCs harvested from CU spontaneously released significantly (P < 0.01) greater amounts of sIL-6R (881.8 +/- 80.1 pg/mL), as compared with CON (267.5 +/- 26.5 pg/mL), UR (258.4 +/- 38.1 pg/mL), and PMMA (288.4 +/- 24.6 pg/mL). Under mitogenic stimulation, the sIL-6R release was significantly (P < 0.01) increased in all groups. The greater PBMC production of sIL-6R in CU was followed by significantly (P < 0.01) higher levels of circulating soluble receptors (48.7 +/- 2.5 ng/mL, 60%), as compared with CON (30.5 +/- 1.9 ng/mL). UR also showed high circulating levels of sIL-6R (53.3 +/- 5.9 ng/mL), probably secondary to an impaired urinary excretion. Circulating levels of sIL-6R in PMMA were comparable to CON (30.3 +/- 3.3 ng/mL). Either the absence of monocyte activation or the adsorption of sIL-6R on the hydrophobic PMMA surface could explain this finding. These results suggest an important role for poor dialysis biocompatibility of CU on the release of sIL-6R, which increases sIL-6R plasma levels, thereby enhancing the inflammatory effects of IL-6.

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

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. 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). 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). 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.

The Effective Removal of Proinflammatory Cytokines by Continuous Hemofiltration with a Polymethylmethacrylate Membrane Following Severe Burn Injury: Report of Three Cases

The Effective Removal of Proinflammatory Cytokines by Continuous Hemofiltration with a Polymethylmethacrylate Membrane Following Severe Burn Injury: Report of Three Cases

Interleukin-6, interleukin-8 and monocyte chemotactic peptide-1 gene expression and protein synthesis are independently modulated by hemodialysis membranes

Uremia produces a wide range of abnormalities of the immune system. Blood-membrane interaction in hemodialysis results in activation and severe dysfunction of peripheral blood mononuclear cells (PBMC). However, the question of whether the use of different dialytic membranes may improve PBMC dysfunctions remains unanswered. To address this issue, the spontaneous interleukin (IL)-6, IL-8 and monocyte chemotactic peptide-1 (MCP-1) gene expression and protein release were studied in PBMC isolated from 7 healthy subjects, 8 uremic patients on conservative therapy and 8 uremic patients undergoing subsequent one month periods of hemodialysis with cuprophan (CU) and high-flux noncomplement activating membranes, polymethylmethacrylate (PMMA) and polyamide (PA). At the end of each period of treatment, PBMC were harvested at the beginning (T0) and after 180 minutes of dialysis (T180), and then were cultured in complete medium. IL-6, IL-8 and MCP-1 mRNA expression were studied by RT-PCR. In addition, MCP-1 gene expression was evaluated also by in situ hybridization. Cytokines released in the supernatant were measured by ELISA. Compared to the control group, PBMC from uremic patients on conservative therapy and treated by CU showed a clear reduction in the cytokine release, while PMMA and PA membranes were able to normalize IL-6, IL-8 and MCP-1 protein concentration, which had been reduced by CU treatment. Interestingly, at T0, mRNA expression for all three cytokines was increased in the patients treated by CU, when compared to the control group and the uremic patients on conservative therapy. A further up-regulation was observed at T180. PMMA and PA treatment, despite increasing the cytokine secretion, significantly reduced the dialysis-induced cytokine gene expression. PBMC exposure to CU membranes results in cytokine mRNA overexpression associated with a paradoxically reduced protein release. In contrast, long-term hemodialysis with synthetic high-flux membranes reduces IL-6, IL-8 and MCP-1 gene expression and improves the ability of PBMC to secrete these cytokines. The reduced cytokine secretion during bioincompatible dialysis may reflect a PBMC adaptation that protects uremic patients against the inflammatory effects of persistent cytokine release.