Dracaena sanderiana endophytic bacteria interactions: Effect of endophyte inoculation on bisphenol A removal.

Bisphenol A (BPA) is one of the most abundant endocrine-disrupting compounds which is found in the aquatic environment. However, actual knowledge regarding the effect of plant-bacteria interactions on enhancing BPA removal is still lacking. In the present study, Dracaena sanderiana endophytic bacteria interactions were investigated to evaluate the effect of bacterial inoculation on BPA removal under hydroponic conditions. Two plant growth-promoting (PGP) bacterial strains, Bacillus thuringiensis and Pantoea dispersa, which have high BPA tolerance and can utilize BPA for growth, were used as plant inocula. P. dispersa-inoculated plants showed the highest BPA removal efficiency at 92.32 ±â€¯1.23% compared to other inoculated and non-inoculated plants. This was due to a higher population of the endophytic inoculum within the plant tissues which resulted in maintained levels of indole-3-acetic acid (IAA) for the plant's physiological needs and lower levels of reactive oxygen species (ROS). In contrast, B. thuringiensis-inoculated plants had a lower BPA removal efficiency. However, individual B. thuringiensis possessed a significantly higher BPA removal efficiency compared to P. dispersa. This study provides convincing evidence that not all PGP endophytic bacteria-plant interactions could improve the BPA removal efficiency. Different inocula and inoculation times should be investigated before using plant inoculation to enhance phytoremediation.

Phytoremediation of bisphenol A and total dissolved solids by the mangrove plant, Bruguiera gymnorhiza.

Bruguiera gymnorhiza, an evergreen mangrove tree, is tolerant of bisphenol A (BPA) and has potential BPA removal capability. BPA is highly toxic to plants at high concentrations, wherein they exhibit damaged symptoms such as chlorosis, necrosis, and wilting. The LD50 of BPA toxicity for this plant was statistically estimated to be 39.97 mg L(-1). B. gymnorhiza can reduce COD from 15408 +/- 246 to 49 +/- 30 mg L(-1) by (approximately 99% reduction of the initial value) and can reduce content to levels below the industrial effluent standard of Thailand (<120 mg L(-1)) within 48 days. This plant can completely remove BPA from the solution within 51 days of treatment. Polysaccharides and organic acids were found in the solution and were caused by plant response to the toxicity of BPA. In addition, B. gymnorrhiza can also reduce total dissolved solids (TDS) and salinity in real wastewater. Therefore, B. gymnorrhiza has potential for removal of BPA and TDS in contaminated in wastewater.

Bisphenol A removal by the Dracaena plant and the role of plant-associating bacteria.

Dracaena sanderiana and Dracaena fragrans plants, as representatives of native, tropical, evergreen plants with fibrous root systems, were evaluated for bisphenol A (BPA) tolerance and uptake capability. D. sanderiana demonstrated significantly higher BPA removal capability than D. fragrans. Therefore, it was chosen for further study. D. sanderiana tolerated BPA toxicity levels up to 80 microM, while higher BPA concentrations damaged the plant. In the sterile hydroponic system with an initial BPA concentration of 20 microM, the plant could uptake approximately 50% of the BPA. The plant's ability to translocate BPA was confirmed by the detection of BPA that accumulated at the roots and stems, but not at the leaves of the plant. Upon BPA exposure, the D. sanderiana secreted extracellular plant mucilage as a protective barrier to the toxic compound. In the non-sterile treatment, the BPA dissipation was contributed not only by the D. sanderiana plant, but also by the co-existing microbes. The BPA reached 85% of the initial concentration at 20 microM. Among the six plant-associating bacterial isolates, Bacillus cereus strain BPW4 and Enterobacter sp. strain BPW5 colonized the D. sanderiana root surface and facilitated BPA dissipation in the hydroponic treatment system. In addition, the success of the BPA treatment in the hazardous waste landfill leachate demonstrated the potential application of D. sanderiana plant in the phytoremediation of BPA contaminated wastewater or industrial leachate.

[Economic aspects of intensive care medicine--cost and reimbursement according to diagnosis related grouping]. / Okonomische Aspekte in der Intensivmedizin: Kosten und Reimbursement unter DRG-Bedingungen 2004.

We analyse relevant modifications of the new German diagnosis related reimbursement system for 2004. It is difficult to judge the consequences of financing intensive care systems by such flat rates. In our surgical ICU total treatment costs were 1 050.-euro /day and 11 530.-euro /patient. Comparison of our total costs and German federal calculation 2003 for long-term ventilation revealed that our costs resulting from a tertiary unit topped the average by 36-60 %. Already the present reimbursement was not cost rewarding. Evaluation according to the 2003 criteria resulted in profound further deterioration to a cost covering of only 49 %. The 2004 system, however, allows for better differentiation of patients and should result in improved reimbursement of long-term ventilation. Further professional analysis of the DRG system is essential for its "learning" development.

Factors affecting lead leaching from microwavable plastic ware made with lead-containing pigments.

Although food contact polymers do not normally contain lead, it is suspected that lead may be leached from some microwavable plastic ware items made in Thailand with lead-containing pigments. The purpose of this study was to examine relationships with regard to lead leached from microwavable plastic ware. Four factors were studied: pH, heat level, extraction time, and number of repeated extractions. A total of 243 samples of microwavable plastic ware items locally manufactured in Thailand were used. This study used three pH values (3.5, 4.5, and 6.5) and three heat levels (levels 3, 6, and 9 [170, 500, and 850 W, respectively]). Acetic acid was used both as the extracting agent and for adjusting the pH. Samples were collected at each level at 1, 3, and 5 min, and the amount of leached lead was measured with an atomic adsorption spectrometer. The results of this study show that pH, heat, and extraction time affected the amount of lead leaching from microwavable plastic ware. The amount of lead leaching increased with decreasing pH but increased with increasing heat level and extraction time. On the basis of these three factors, the results of this study indicate that the pH of the extractant (r = -0.592, P < 0.01), the heat level of extraction (r = 0.293, P < 0.01), the extraction time (r = 0.226, P < 0.01), and the number of extractions (r = -0.153, P < 0.01) are related to lead leaching from microwavable plastic ware. The relationship between the pH of the extractant, the heat level of extraction, and the extraction time significantly moderated lead leaching from microwavable plastic ware (R2 = 0.511, P < 0.001). For all factors, the amount of lead leaching was lower than the permissible level of 1 mg/liter specified by the Minister of Public Health. In conclusion, a combination of high acid, prolonged heating, and extraction time accelerated the amount of lead leaching from microwavable plastic ware, but the incidence of lead leaching was negligible.

The thrombin antagonist hirudin fails to inhibit endotoxin-induced leukocyte/endothelial cell interaction and microvascular perfusion failure.

Besides its central role in coagulatory pathways, thrombin is known to be a key mediator of macrophage and granulocyte activation in vitro. During recent years the concept of thrombin inhibition by the specific thrombin inhibitor, hirudin, has been established to treat septic disorders. Since basic mechanisms of sepsis include leukocyte/endothelial cell interaction and deterioration of capillary perfusion, we hypothesized that hirudin modulates leukocyte activation and microvascular injury. Severe endotoxemia was induced in Syrian hamsters by intravenous administration of endotoxin (lipopolysaccharide [LPS], E. coli, 2mg/kg) at 0 h. Hirudin (0.25 mg/kg/h) was substituted intravenously during the 4 h after the induction of endotoxemia (n = 7, hirudin). In control animals (n = 6, control) LPS was given without hirudin substitution. In skinfold chamber preparations leukocyte/endothelial cell interaction and functional capillary density (FCD, measure of capillary perfusion) were analyzed during a 24-h period after LPS injection using intravital fluorescence microscopy. Hirudin effectively normalized thromboplastin time and antithrombin activity when compared to controls (P < 0.05, ANOVA). However, hirudin did not attenuate LPS-induced arteriolar and venular leukocyte adherence, and even tended to increase leukocyte adherence after 24 h (P > 0.05, MANOVA). In parallel, addition of hirudin led to a significant deterioration of FCD over time when compared to controls (hirudin: baseline = 171 +/- 19 cm(-1) versus 16 +/- 9 at 24 h; control: baseline = 150 +/- 20 cm(-1) versus 62 +/- 18 at 24 h; P < 0.05). The fall in FCD in hirudin animals was associated with a significant increase of wet-to-dry weight ratios in lung, kidney, muscle, and small intestine (P < 0.05 versus control, ANOVA). Thus our study does not indicate a protective effect of hirudin on microcirculation during endotoxemia, despite an improvement of coagulatory parameters. This result may at least in part explain the lack of efficacy of hirudin on lethality during endotoxemia and sepsis.

Antithrombin reduces leukocyte adhesion during chronic endotoxemia by modulation of the cyclooxygenase pathway.

Antithrombin (AT) is known as the most important natural inhibitor of thrombin activity and has been shown to improve distinct clinical parameters during the course of septic (endotoxin)-induced multiple organ dysfunction. We hypothesized that AT acts by inhibiting leukocyte activation and microvascular injury via the promotion of endothelial release of PGI(2), and therefore, we studied the effects of AT on leukocyte/endothelial cell interaction and microvascular perfusion during endotoxemia. In a skinfold preparation of Syrian hamsters, severe endotoxemia was induced by repeated administration of endotoxin intravenously [lipopolysaccharide (LPS), Escherichia coli, 2 mg/kg] at 0 and 48 h. AT (250 IU/kg) was administered intravenously at 0, 24, and 48 h (n = 6, AT group). In control animals (n = 5, control), LPS was given without AT supplementation. By intravital fluorescence microscopy, leukocyte-endothelial cell interaction and functional capillary density (FCD; measure of capillary perfusion) were analyzed during a 72-h period after the first LPS injection. AT significantly attenuated LPS-induced arteriolar and venular leukocyte adherence after both the first and the second LPS injection [P < 0.01, measures analysis of variance (MANOVA)]. In parallel, AT was effective in preventing LPS-induced depression of FCD after the first and the second LPS administration (P < 0.05, MANOVA). By pretreatment with the cyclooxygenase inhibitor indomethacin (n = 6), effects of AT on leukocyte adherence and FCD were found completely abolished. Thus our study indicates that AT exerts its beneficial effects in endotoxemia by reducing leukocyte-endothelial cell interaction and microvascular perfusion failure probably via liberation of prostacyclin from endothelial cells.

Incidence and mortality of severe sepsis in surgical intensive care patients: the influence of patient gender on disease process and outcome.

OBJECTIVE: Laboratory studies demonstrated significant detrimental effects of male sex-steroids (testosterone) on immune functions following hemorrhagic shock and soft-tissue trauma. Moreover, better survival of female mice subjected to severe sepsis was observed when compared to male animals. The aims of the present study were to evaluate whether or not gender differences regarding incidence and mortality of severe sepsis do exist in surgical intensive care patients and to elucidate the influence of patient age on incidence and mortality of severe sepsis/septic shock. DESIGN: Data base review of prospectively collected data from surgical intensive care patients. SETTING: Surgical intensive care unit of the department of surgery of a university hospital. PATIENTS: Prospectively collected data of 4,218 intensive care patients (2,709 male, 1,509 female). RESULTS: Significantly fewer female patients were referred to the intensive care unit (6.6 % vs 10.8 % of all patients; P < 0.05) leading to a significantly smaller proportion of female intensive care patients (35.8% vs 64.2%). No gender differences regarding number of failing organs or surgical procedure (exception vascular surgery) were observed in patients with and without severe sepsis/septic shock, indicating that the patients studied are comparable regarding general health prior to admission to SICU. Among all female patients referred to SICU only 7.6 % developed severe sepsis/septic shock, while 10.4% of all male patients suffered from severe sepsis or septic shock (P < 0.05). This gender difference results from a significantly lower incidence of severe sepsis/ septic shock in female patients between 60 and 79 years. No gender difference regarding mortality rates of severe sepsis/septic shock was observed (men 64.9 %, women 65.5%). CONCLUSIONS: Our results indicate a significantly smaller number of female patients requiring intensive care as well as a significantly lower incidence of severe sepsis/septic shock in female intensive care patients. Mortality from severe sepsis/ septic shock, however, is not affected by gender.

A chronic model for intravital microscopic study of microcirculatory disorders and leukocyte/endothelial cell interaction during normotensive endotoxemia.

Sepsis-induced microvascular leukocyte/endothelial cell interaction may result in a deterioration of capillary perfusion that finally leads to septic organ dysfunction. The aim of the present study was to characterize a novel, sublethal, two-hit model of chronic systemic sepsis that allows the repeated analysis of microcirculation by intravital microscopy. In Syrian golden hamsters the effect of a single i.v. endotoxin (LPS, 2 mg/kg, E. coli) injection (SH-LPS group, n = 5 animals) vs. a double LPS injection (DH-LPS group, n = 6 animals) was analyzed. After monitoring baseline parameters (t1), measurements were performed at 30 min (t2), 3 h (t3), 8 h (t4), 24 h (t5), 48 h (t6), 56 h (t7) and 72 h (t8) (both groups) after initial LPS exposure. In DH-LPS animals, a second LPS injection (2 mg/kg) was given at t6 (48 h). Intravital fluorescence microscopy was performed in a dorsal skin fold chamber preparation and allowed determination of leukocyte-endothelial cell interaction (leukocyte rolling and sticking), and measurement of functional capillary density (FCD), which served as a measure of capillary perfusion. The first LPS injection comparably altered leukocyte/endothelial cell interaction and capillary perfusion in both groups (t1-t6, P > 0.05, MANOVA). Between t6 and t8 leukocyte adherence decreased in SH-LPS animals, whereas in DH-LPS animals adherence remained constantly elevated (SH-LPS: -53.0 +/- 6.2% between t6 and t8 vs. DH-LPS: -3 +/- 5; P < 0.05). The ongoing inflammatory response in DH-LPS animals was associated with a progressive deterioration of FCD, whereas FCD remained constant in SH-LPS animals (DH-LPS: -71.5 +/- 17% between t6 and t8 vs. SH-LPS: 3.0 +/- 13%; P < 0.05). In parallel, coagulatory parameters were found significantly altered only in DH-LPS animals but not in SH-LPS animals. We conclude that "double hit" LPS exposure is an appropriate model (i) to analyze repeatedly over time microcirculatory disorders under conditions of persistent endotoxemia-induced inflammatory response, and (ii) to prove the effectiveness of novel anti-inflammatory strategies.

Hemofiltrate from patients with severe sepsis and depressed left ventricular contractility contains cardiotoxic compounds.

Myocardial dysfunction due to sepsis is common in patients with multiple organ dysfunction syndrome and is believed to be produced by inflammatory mediators. Some of these mediators may be eliminated by continuous hemofiltration, which is a standard procedure in an ICU for renal replacement therapy. This study was designed to directly compare the effects of ultrafiltrates from patients with sepsis (UFs) with ultrafiltrates from healthy volunteers (UFh) in well-characterized cardiomyocyte culture systems. Isovolemic hemofiltration (filtration rate: 2 L/h, polyamide membrane) was performed during 12 hours in 5 patients with severe sepsis (Elebute Score >20) and simultaneously reduced left ventricular contractility (left ventricular stroke work index [LVSWI] <30 g m/m2) and in 5 healthy volunteers. Inflammatory mediator concentrations (interleukin [IL]-1beta, IL-6, IL-8, tumor necrosis factor [TNF] alpha, C3a, and C5a) were measured in plasma and ultrafiltrate samples taken shortly after the beginning of the hemofiltration procedure. Cell culture experiments were done comparing UFs with UFh by using spontaneously beating or electrically driven neonatal rat cardiomyocyte cultures. UFs contained significantly higher amounts of IL-1, IL-8, and C3a when compared to UFh. Simultaneously, UFs induced a decrease in the contraction frequency of electrically-stimulated cardiomyocytes, whereas UFh had no effect. The cardiotoxic effect could be reversed by the addition of a high concentration (2.4 mM) of Ca++. Hemofiltration did not alter parameters of cardiac performance during 12 hours in patients with sepsis. UFs induced significant cardiotoxic effects in rat cardiomyocytes, whereas UFh showed no cardiotoxicity. Contact of blood with the hemofiltration membrane did not induce activation of cardiotoxic mediators. Significantly higher filtration rates may be required to improve left ventricular contractility in patients with sepsis by hemofiltration.

Effect of antithrombin III supplementation on inflammatory response in patients with severe sepsis.

Antithrombin III (AT III) is an important inhibitor of thrombin activity, as well as of many other proteases of the coagulation system. AT III administration showed beneficial effects on septic multiple organ dysfunction in clinical and experimental studies. It was the aim of this study to determine whether continuous long-term AT III supplementation alters the systemic inflammatory response in patients with severe sepsis. In a prospective study, 29 surgical patients with severe sepsis were randomly assigned to receive either conventional intensive care treatment (n = 15, control group) or additional AT III supplementation to achieve a plasma AT III activity >120% during a 14 day study period (n = 14, AT III group). Plasma concentrations of interleukin (IL)-6 and IL-8 and of the circulating soluble adhesion molecules sICAM-1 and sE-selectin, as well as of PMN elastase, were determined daily. Additionally, total leukocyte count and C-reactive protein (CRP) were measured daily, and body temperature was registered. Compared to control patients, a down-regulation of plasma IL-6 was observed in the AT III group (p < or = .01). AT III supplementation prevented the continuous increase in sICAM-1 plasma concentration observed in control patients and led to a significant fall in soluble sE-selectin and CRP concentration (p < or = .01). This fall corresponded to a down-regulation of body temperature over time (p < or = .01). There was no AT III effect on IL-8, PMN-elastase concentration, or total leukocyte count. Our results show that long-term AT III supplementation attenuates the systemic inflammatory response in patients with severe sepsis. The down-regulation of IL-6 may also explain the fall in endothelium-derived adhesion molecules and may represent the molecular basis by which AT III exerts its beneficial effects on organ function.

Antithrombin III supplementation in severe sepsis: beneficial effects on organ dysfunction.

Activation of thrombin and of the coagulation system plays an important role in the pathophysiology of sepsis-associated organ dysfunction. Antithrombin III (AT III) is a natural inhibitor of thrombin, a central procoagulatory factor with pleiotropic activities. Experimental supplementation of AT III improved coagulation parameters and ameliorated organ dysfunction. To determine whether long-term AT III supplementation has beneficial effects on organ function, we conducted a randomized, prospective study in surgical patients with severe sepsis. The study evaluated the long-term effect of AT III supplementation (duration of treatment: 14 days). After randomization (AT III vs. control group), AT III was infused continuously over 14 days to obtain plasma AT III activities > 120%. Forty consecutive patients were recruited (20 AT III/20 control group). Eleven patients had a rapid fatal course and did not met the criterion of a 14 day treatment period. From these 11 patients, 8 patients (5 AT III/3 control group) died within 72 h due to septic shock. The remaining 14 AT III patients and 15 controls survived 14 days and showed no differences in baseline parameters of organ function. AT III caused a disappearance of disseminated intravascular coagulation (DIC) in all patients with DIC, whereas in control patients, the frequency of DIC remained constant (p < .05). In AT III patients a progressive increase in oxygenation index (PaO2/FiO2 ratio) and a continuous decrease in pulmonary hypertension index (mean pulmonary artery pressure/mean arterial pressure (PAP/MAP) ratio) indicated an improvement of lung function (p < .05 vs. control). AT III prevented the continuous rise in total serum bilirubin concentration observed in control patients and diminished the frequency of artificial renal support therapy (p < .05). Long-term supplementation with AT III may improve lung function and prevent the development of septic liver and kidney failure in patients with severe sepsis.

Tumor necrosis factor measurement and use of different anticoagulants: possible interference in plasma samples and supernatants from endotoxin-stimulated monocytes.

OBJECTIVE AND DESIGN: Unfractionated heparin is frequently used as an anticoagulant during blood sampling and in cell culture experiments. In the present study we investigated whether heparin and other anticoagulants (citrate and EDTA) interfered with measurements of plasma tumor necrosis factor alpha (TNF alpha) concentrations or with TNF alpha release from endotoxin-stimulated monocytes. MATERIAL AND METHODS: TNF alpha was measured by a WEHI 164 bioassay in the plasma of 16 septic patients anticoagulated with heparin, citrate, or EDTA. Anticoagulants were incubated with the bioassay cell line and cell lysis was monitored. To exclude falsely low TNF alpha concentrations, anticoagulants were incubated in increasing amounts with human recombinant TNF alpha/saline solution, and rTNF alpha recovery was measured either with the WEHI 164 bioassay or an ELISA test. Further, anticoagulants were incubated with monocytes isolated from healthy volunteers and stimulated with endotoxin. Supernatants were analyzed for TNF alpha with both test systems. RESULTS: No biologically active TNF alpha was detected in the plasma with heparin anticoagulation, whereas with citrate, reproducible, TNF alpha-induced cytotoxicity was detectable in blood samples of 13 of the 16 patients. Anticoagulation with EDTA resulted in fairly high, variable and poorly reproducible TNF alpha values. Only EDTA produced falsely high values by unspecific lysis of WEHI cells. Only heparin at a concentration of 20 I.U./ml or more was found to produce falsely low values by interaction with the TNF alpha bioassay, but also with the ELISA test. In monocyte culture experiments, heparin significantly attenuated the stimulatory effect of endotoxin on TNF alpha release already at the lowest concentration tested (25 I.U./ml). CONCLUSIONS: Heparin and EDTA may have significant adverse effects on TNF alpha measurement when used for blood sampling. Citrate does not interfere with the TNF alpha bioassay or ELISA, and seems, therefore, to be the anticoagulant of choice. Due to intrinsic interactions with various cell systems (including the WEHI cell and monocytes), one should be careful in using heparin in cell culture studies in which effects of TNF alpha or of endotoxin are being studied.

Effect of hemofiltration on hemodynamics and systemic concentrations of anaphylatoxins and cytokines in human sepsis.

OBJECTIVE: To determine whether hemofiltration (HF) can eliminate cytokines and complement components and alter systemic hemodynamics in patients with severe sepsis. DESIGN: Prospective observation study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: 16 patients with severe sepsis. INTERVENTIONS: Continuous zero-balanced HF without dialysis (ultrafiltrate rate 2 l/h) was performed in addition to pulmonary artery catheterization, arterial cannulation, and standard intensive care treatment. MEASUREMENTS AND MAIN RESULTS: Plasma and ultrafiltrate concentrations of cytokines (the interleukins IL-1 beta, IL-6, IL-8, and tumor necrosis factor alpha) and of complement components (C3adesArg, C5adesArg) were measured after starting HF (t0) and 4 h (t4) and 12 h later (t12). Hemodynamic variables including mean arterial pressure (MAP), mean central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were serially determined. During HF, cytokine plasma concentrations remained constant. However, C3adesArg and C5adesArg plasma concentrations showed a significant decline during 12-h HF (C3adesArg: t0 = 676.9 +/- 99.7 ng/ml vs t12 = 467.8 +/- 71, p < 0.01; C5adesArg: 26.6 +/- 4.7 ng/ml vs 17.6 +/- 6.2, p < 0.01). HF resulted in a significant increase over time in systemic vascular resistance (SVR) and MAP (SVR at t0: 669 +/- 85 dyne.s/cm5 vs SVR at t12: 864 +/- 75, p < 0.01; MAP at t0: 69.9 +/- 3.5 mmHg vs MAP at t12: 82.2 +/- 3.7, p < 0.01). CONCLUSIONS: HF effectively eliminated the anaphylatoxins C3adesArg and C5adesArg during sepsis. There was also a significant rise in SVR and MAP during high volume HF. Therefore, HF may represent a new modality for removal of anaphylatoxins and may, thereby, deserve clinical testing in patients with severe sepsis.

[Intensive therapy in surgery. Value, goals and outcome]. / Intensivtherapie in der Chirurgie. Sinn, Ziele und Erreichtes.

Intensive care is one tool of medicine. Resuscitation, treatment of organ failure, maintenance of homeostasis and prophylaxis of postoperative complications are it's duties. Over the last three decades the results of critical care medicine have significantly improved and the mortality rate has been halved. Not only the better understanding of development and significance of multiple organ failure, but also the re-evaluation of the role of age and co-morbidity have contributed to this improvement. Also, increased experience and competence of the physician, as well as a growing knowledge of systemic inflammatory response syndrome (SIRS) and the sepsis syndrome have promoted this progress. Hemofiltration is a novel method of neutralizing sepsis-related mediators and cytokines from the circulation.

Hemofiltration in human sepsis: evidence for elimination of immunomodulatory substances.

Continuous hemofiltration is widely used for renal replacement therapy in patients with acute renal failure. It has been suggested that hemofiltration may also eliminate toxic mediators thought to be important in the pathophysiology of sepsis. The present study examined whether hemofiltration can activate or eliminate inflammatory mediators in patients with sepsis, and whether ultrafiltrate can alter specific functions of peripheral blood mononuclear leukocytes (PBMC) in vitro. Veno-venous hemofiltration was performed in 16 patients and in 5 healthy volunteers. Pre-filter (afferent), post-filter (efferent) and ultrafiltrate concentrations of cytokines (IL-1 beta, IL-6, IL-8, TNF alpha) and of complement components (C3, C3adesArg, C5adesArg, terminal complement complex) were measured after the beginning of hemofiltration (t0), and 60 minutes later (t60). PBMC, and monocyte and lymphocyte subfractions were incubated with ultrafiltrate, and cytokines were determined in the supernatants. Hemofiltration did not induce significant mediator activation. There was no evidence for significant cytokine elimination. However, pre-filter C3adesArg concentration showed a significant decline during hemofiltration (patients: t0 = 676.9 +/- 99.7 ng/ml, t60 = 545.4 +/- 83.2, P < 0.001; volunteers: t0 = 54.8 +/- 13.3 ng/ml, t60 = 33.9 +/- 10.7, P < 0.001). Ultrafiltrate from septic patients significantly stimulated PBMC and monocyte TNF alpha release, but suppressed lymphocyte IL-2 and IL-6 production. Ultrafiltrate from volunteers was without effect. Hemofiltration effectively eliminates certain mediators such as C3adesArg. Ultrafiltrate contains compounds with significant immunomodulatory qualities. Therefore, hemofiltration may represent a new modality for removal of immunomodulatory mediators.