Hypoxia-inducible factor-dependent induction of netrin-1 dampens inflammation caused by hypoxia.

The neuronal guidance molecule netrin-1 is linked to the coordination of inflammatory responses. Given that mucosal surfaces are particularly prone to hypoxia-elicited inflammation, we sought to determine the function of netrin-1 in hypoxia-induced inflammation. We detected hypoxia-inducible factor 1alpha (HIF-1alpha)-dependent induction of expression of the gene encoding netrin-1 (Ntn1) in hypoxic epithelia. Neutrophil transepithelial migration studies showed that by engaging A2B adenosine receptor (A2BAR) on neutrophils, netrin-1 attenuated neutrophil transmigration. Exogenous netrin-1 suppressed hypoxia-elicited inflammation in wild-type but not in A2BAR-deficient mice, and inflammatory hypoxia was enhanced in Ntn1(+/-) mice relative to that in Ntn1(+/+) mice. Our studies demonstrate that HIF-1alpha-dependent induction of netrin-1 attenuates hypoxia-elicited inflammation at mucosal surfaces.

Cytomegalovirus reactivation and associated outcome of critically ill patients with severe sepsis.

INTRODUCTION: Sepsis has been identified as a risk factor for human cytomegalovirus (CMV) reactivation in critically ill patients. However, the contribution of CMV reactivation on morbidity and mortality is still controversial. Therefore, we analyzed the incidence and impact of CMV reactivation on outcome in patients with severe sepsis. METHODS: In a prospective longitudinal double-blinded observational study, 97 adult nonimmunosuppressed CMV-seropositive patients with new onset of severe sepsis were included. Leukocytes, plasma and tracheal secretions were examined weekly for CMV-DNA by PCR. Tracheal secretions were additionally tested for HSV (Herpes Simplex Virus)-DNA. The influence of CMV-reactivation on the endpoints was analysed by Cox proportional-hazard regression analysis. Time-dependency was evaluated by landmark analysis. RESULTS: Six out 97 died and five were discharged from the hospital within 72 hours and were excluded of the analysis. CMV reactivation occurred in 35 of the 86 (40.69%) analysed patients. HSV infection occurred in 23 of the 35 (65.7%) CMV reactivators. In 10 patients CMV-plasma-DNAemia appeared with a DNA-content below 600 copies/ml in four cases and a peak amount of 2,830 copies/ml on average. In patients with and without CMV reactivation mortality rates were similar (37.1% vs. 35.3%, P = 0.861), respectively. However, in the multivariate COX regression analyses CMV reactivation was independently associated with increased length of stay in the ICU (30.0, interquartile range 14 to 48 vs. 12.0, interquartile range 7 to 19 days; HR (hazard ratio) 3.365; 95% CI (confidence interval) 1.233 to 9.183, P = 0.018) and in the hospital (33.0, interquartile range 24 to 62 vs. 16.0, interquartile range 10 to 24 days, HR 3.3, 95% CI 1.78 to 6.25, P < 0.001) as well as prolonged mechanical ventilation (22.0, interquartile range 6 to 36 vs. 7.5, interquartile range 5 to 15.5 days; HR 2.6,CI 95% 1.39 to 4.94; P < 0.001) and impaired pulmonary gas exchange (six days, interquartile range 1 to 17, vs. three, interquartile range 1 to 7, days in reactivators vs. non-reactivators, P = 0.038). HSV reactivation proved not to be a risk factor for these adverse effects. CONCLUSIONS: These data indicate an independent correlation between CMV reactivation and increased morbidity in the well-defined group of nonimmunosuppressed patients with severe sepsis, but CMV reactivation had no impact on mortality in this group with low CMV-DNA plasma levels. Thus, the potential harms and benefits of antiviral treatment have to be weighed cautiously in patients with severe sepsis or septic shock.

ImageStream cytometry extends the analysis of phagocytosis and oxidative burst.

AIM: Phagocytosis is often measured using conventional microscopy and flow cytometry. ImageStream cytometry is a new technology that combines the advantages of both methods, enabling statistically robust microscopic applications. We compared ImageStream cytometry to flow cytometry in a whole blood model of phagocytosis with viable, fluorescence-marked Staphylococcus aureus. We furthermore measured the co-localization of intracellular bacteria to sites of oxidative burst, as well as changes in cell size and actin levels as a result of phagocytosis. EXPERIMENTAL DESIGN: Fluorescence-labeled S. aureus in a ratio of 5:1 bacteria per leukocyte were added to whole blood. Phagocytosis was stopped at different time points. After staining of neutrophils and lysis of erythrocytes, samples were analysed by ImageStream cytometry and flow cytometry. RESULTS: Phagocytosis and oxidative burst determined by flow cytometry and ImageStream cytometry showed strong correlation. In contrast to flow cytometry, ImageStream cytometry easily detected and excluded extracellular adherent bacteria from the measurement of phagocytosis, and enumerated the bacteria within each neutrophil. Using the Bright Detail Similarity score, we identified a subset of neutrophils with intracellular bacteria co-localized to sites of oxidative burst activity. Phagocytosis resulted in an increase in cell size and actin polymerization as determined by an increase in phalloidin fluorescence intensity. CONCLUSIONS: We describe a simple whole blood image-based method for measuring bacterial phagocytosis and oxidative burst. ImageStream cytometry provides the spatial resolution to determine the number of bacteria ingested and the sub-cellular localization and trafficking patterns that enables a more complete evaluation of the phagocytic process.

Netrin-1 dampens pulmonary inflammation during acute lung injury.

RATIONALE: Acute lung injury (ALI) is an inflammatory disorder characterized by hypoxemia and diffuse infiltration of neutrophils into the alveolar space. The migration and extravasation of neutrophils is guided through positive guidance cues, such as chemokines. Recent work has identified the neuronal guidance protein netrin-1 to be a negative guidance cue for leukocyte migration and to hold antiinflammatory potential. OBJECTIVES: To test the role of pulmonary netrin-1 during ALI. METHODS: Pulmonary netrin-1 expression was evaluated during acute inflammation in vitro and in vivo; the netrin-1 promoter was studied using pGL4 luciferase reporter. ALI was induced through LPS inhalation and mechanical ventilation in wild-type, Ntn1(+/-), and A2BAR(-/-) animals. Exogenous netrin-1 was used to evaluate its impact on pulmonary inflammation. MEASUREMENTS AND MAIN RESULTS: Wild-type animals demonstrated repression of pulmonary netrin-1 after LPS inhalation. In vitro studies confirmed the repression of netrin-1. Studies in the putative netrin-1 promoter identified a nuclear factor-kappaB-dependent mechanism to be involved in this repression. Ntn1(+/-) animals demonstrated increased inflammatory changes after LPS inhalation compared with Ntn1(+/+) animals. Reconstitution with netrin-1 dampened the infiltration of neutrophils and cytokine production in the alveolar space. This effect was dependent on the adenosine 2b receptor. The importance of netrin-1 for the control of pulmonary inflammation could be corroborated in a model of ventilator-induced lung injury. CONCLUSIONS: Pulmonary netrin-1 levels are repressed during ALI. This results in pronounced pulmonary damage, an increased infiltration of neutrophils, and increased pulmonary inflammation. Exogenous netrin-1 significantly dampens the extent of ALI through the adenosine 2B receptor.

[Resuscitation algorithms for cardiac arrest and arrhythmias]. / Reanimation: Was ist neu? Notfallbehandlung von Herzstillstand und Arrhythmien.

Recently, guidelines for cardiopulmonary resuscitation have been updated by the European Resuscitation Council. Here we focus on cardiac arrest and arrhythmia algorithms for primary healthcare providers incorporating new recommendations.

Iloprost preserves renal oxygenation and restores kidney function in endotoxemia-related acute renal failure in the rat.

OBJECTIVE: To investigate that exogenous prostacyclin would counterbalance an endotoxemia-induced intrarenal vasoconstriction and would therefore have beneficial effects on kidney function. DESIGN: Prospective, randomized, controlled study. SETTING: University medical center research laboratory. SUBJECTS: Eighteen male Wistar rats. INTERVENTIONS: In anesthetized and ventilated animals, arterial blood pressure (mean arterial blood pressure [MAP]) and renal blood flow (RBF) were recorded. Renal microvascular Po2 (muPo2) and renal venous Po2 were continuously measured by phosphorescence lifetime technique. All animals received a 30-minute infusion of lipopolysaccharide (LPS) (2.5 mg/kg) to induce endotoxemia. One group of rats was not resuscitated. A second group received fluid resuscitation 90 minutes after stop of LPS infusion. In a third group of rats, the prostacyclin analogue iloprost (100 ng/kg/min) was continuously infused in addition to fluid resuscitation. Furthermore, in all the animals, plasma NOx levels, renal inducible nitric-oxide synthase (iNOS) messenger RNA (mRNA) expression, and creatinine clearance were determined. MEASUREMENTS AND MAIN RESULTS: During LPS infusion, MAP and RBF progressively dropped to 50% of baseline at 120 minutes. After an initial increase in MAP and RBF, start of fluid resuscitation with iloprost resulted in the stabilization of both parameters. All animals became anuric during endotoxemia. Only in animals receiving iloprost was creatinine clearance totally restored at the end of the experiment. Iloprost had no significant effects on average muPo2, but prevented the occurrence of cortical microcirculatory hypoxic areas. NOx levels and iNOS mRNA expression were significantly increased in all animals receiving LPS after 5 hours. There was no difference in NOx concentration between the different groups. In animals receiving iloprost, iNOS mRNA expression was significantly suppressed in the inner medulla. CONCLUSIONS: Iloprost significantly restored kidney function of endotoxemic rats to baseline values. This beneficial effect of iloprost on renal function might be addressed to an improvement in intrarenal oxygenation.

Effects of 1400W and/or nitroglycerin on renal oxygenation and kidney function during endotoxaemia in anaesthetized rats.

1. The pathogenesis of acute renal failure (ARF) in sepsis is multifactorial. The role of nitric oxide (NO) in septic ARF has been a source of controversy. We hypothesized that endotoxaemia-induced exacerbation of inducible nitric oxide synthase (iNOS)-related NO release impairs renal oxygenation and contributes to ARF in anaesthetized rats. 2. In the present study, rats received lipopolysaccharide (2.5 mg/kg) for 30 min. Two hours later, fluid resuscitation was started (HES130; 5 mL/kg per h after a 5 mL/kg bolus) supplemented either by the NO donor nitroglycerin (NTG; 0.5 µg/kg per min after a 2 µg/kg bolus), the selective iNOS inhibitor 1400 W (3 mg/kg per h after a 3 mg/kg bolus) or both. Systemic haemodynamics and renal microvascular Po2 (µPo(2)) were recorded continuously. Furthermore, creatinine clearance, plasma NO(x) (nitrate + nitrite + S-nitrosothiols) levels and the expression of iNOS mRNA were measured. 3. Endotoxaemia reduced renal blood flow, decreased mean arterial pressure, resulted in anuria and was associated with an increase in plasma NO(x) levels and renal iNOS expression. Renal µPo2 deteriorated gradually during endotoxaemia and there was a significant decrease in renal O(2) delivery and consumption. Manipulation of NO levels had no beneficial effect on systemic haemodynamics, renal µPo(2) or creatinine clearance over standard fluid resuscitation. The application of 1400 W+NTG significantly reduced plasma NO(x) levels compared with fluid resuscitation and NTG alone. 4. Neither iNOS inhibition, NO donation nor a combination of both showed beneficial effects on systemic haemodynamics, renal oxygenation and renal function compared with fluid resuscitation alone. Our results question the proposed key role of NO in the pathogenesis of septic ARF in rats.

Cardioprotection by ecto-5'-nucleotidase (CD73) and A2B adenosine receptors.

BACKGROUND: Ecto-5'-nucleotidase (CD73)-dependent adenosine generation has been implicated in tissue protection during acute injury. Once generated, adenosine can activate cell-surface adenosine receptors (A1 AR, A2A AR, A2B AR, A3 AR). In the present study, we define the contribution of adenosine to cardioprotection by ischemic preconditioning. METHODS AND RESULTS: On the basis of observations of CD73 induction by ischemic preconditioning, we found that inhibition or targeted gene deletion of cd73 abolished infarct size-limiting effects. Moreover, 5'-nucleotidase treatment reconstituted cd73-/- mice and attenuated infarct sizes in wild-type mice. Transcriptional profiling of adenosine receptors suggested a contribution of A2B AR because it was selectively induced by ischemic preconditioning. Specifically, in situ ischemic preconditioning conferred cardioprotection in A1 AR-/-, A2A AR-/-, or A3 AR-/- mice but not in A2B AR-/- mice or in wild-type mice after inhibition of the A2B AR. Moreover, A2B AR agonist treatment significantly reduced infarct sizes after ischemia. CONCLUSIONS: Taken together, pharmacological and genetic evidence demonstrate the importance of CD73-dependent adenosine generation and signaling through A2B AR for cardioprotection by ischemic preconditioning and suggests 5'-nucleotidase or A2B AR agonists as therapy for myocardial ischemia.

Treatment with tigecycline of recurrent urosepsis caused by extended-spectrum-beta-lactamase-producing Escherichia coli.

A 25-year-old female was admitted to our intensive care unit with septic shock and multiorgan failure caused by extended-spectrum beta-lactamase-producing Escherichia coli originating from the right renal pelvis. A 16-day course of treatment with meropenem reversed the septic condition, but the infection recurred thereafter. The patient recovered fully after therapy was changed to tigecycline.

The inhibition of human neutrophil phagocytosis and oxidative burst by tricyclic antidepressants.

BACKGROUND: Tricyclic antidepressants are being investigated as long-acting analgesics for topical application in wounds or IV for postoperative pain relief. However, it remains unclear if tricyclic antidepressants affect the host defense and if reported toxic effects on neutrophils are of relevance in this setting. We therefore investigated the effects of amitriptyline, nortriptyline, and fluoxetine on human neutrophil phagocytosis, oxidative burst, and neutrophil toxicity in a human whole blood model. METHODS: Heparinized blood samples from healthy volunteers were incubated with amitriptyline, nortriptyline, or fluoxetine (10(-6) to 10(-3) M) for 0, 1, or 3 h. Staphylococcus aureus in a bacteria:neutrophil ratio of 5:1 and dihydroethidium (for the determination of oxidative burst) were added. Phagocytosis was stopped after 5, 10, 20, and 40 min. After lysis of red blood cells, samples were analyzed by flow cytometry. RESULTS: In concentrations up to 10(-4) M, none of the compounds affected neutrophil phagocytosis and oxidative burst. At 10(-3) M, all three compounds were highly toxic for neutrophils. Amitriptyline preserved morphological integrity, but completely suppressed neutrophil function. Nortriptyline and fluoxetine caused a marked disruption of neutrophils. The effects of the investigated antidepressants were not time-dependent. CONCLUSIONS: Phagocytosis and intracellular host defense are largely unaffected by antidepressants in concentrations of 10(-4) M and below. Our results confirm that antidepressants are highly toxic to neutrophils in millimolar concentrations. The neurotoxic effects and clinical side effects, but not effects on neutrophil functions, therefore, are likely to be the limiting factors in using antidepressants as analgesics.

Efficacy of ketamine in anesthetic dosage for the treatment of refractory complex regional pain syndrome: an open-label phase II study.

OBJECTIVE: Advanced complex regional pain syndrome (CRPS) remains very difficult to treat. While subanesthetic low-dose ketamine has shown promise in early localized CRPS, its use in advanced CRPS has not been as effective. Since ketamine's analgesic potency and duration of effect in neuropathic pain are directly dose-dependant, we investigated the efficacy of ketamine in anesthetic dosage in refractory CRPS patients that had failed available standard therapies. METHODS: Twenty ASA I-III patients suffering from refractory CRPS received ketamine in anesthetic dosage over 5 days. Outcome criteria were pain relief, effect on the movement disorder, quality of life, and ability to work at baseline and up to 6 months following treatment. RESULTS: Significant pain relief was observed at 1, 3, and 6 months following treatment (93.5 +/- 11.1%, 89.4 +/- 17.0%, 79.3 +/- 25.3%; P < 0.001). Complete remission from CRPS was observed at 1 month in all patients, at 3 months in 17, and at 6 months in 16 patients. If relapse occurred, significant pain relief was still attained at 3 and 6 months (59.0 +/- 14.7%, P < 0.004; 50.2 +/- 10.6%, P < 0.002). Quality of life, the associated movement disorder, and the ability to work significantly improved in the majority of patients at 3 and 6 months. CONCLUSIONS: This open-label trial suggests benefit in pain reduction, associated CRPS symptoms, improved quality of life and ability to work following anesthetic ketamine in previously refractory CRPS patients. However, a randomized controlled trial will be necessary to prove its efficacy.

[The intensive care in the German Diagnosis Related Groups-System]. / Die Intensivmedizin im deutschen DRG (Diagnosis Related Groups)-System.

The introduction of a prospective per case reimbursement system in the year 2004 in Germany put the high end intensive care medicine to a considerable financial risk on the basis of risk selection and high maintenance costs. To face this situation, the German Interdisciplinary Union for Intensive Care Medicine (DIVI) suggested to encode intensive care services as a DRG procedure and thus to make them relevant for reimbursement. That is the case now since 2007. The suggested procedure, called " complex intensive care treatment ", is based on a new intensive care scoring system ("Cost Predictor Score") which should quantify the costs per case. This paper provides an introduction into the GR-DRG (German Refined--Diagnosis Related Groups) health care reimbursement system and its financial implications for expensive hospital departments and presents a study carried out in the Anaesthesiological Intensive Care Unit of the Tübingen University Hospital examining the suitability of this new intensive care scoring system.

Memantine treatment of complex regional pain syndrome: a preliminary report of six cases.

OBJECTIVES: Recent studies have confirmed the contribution of the central nervous system (CNS) to the pathogenesis of Complex Regional Pain Syndrome (CRPS), because animal models of neuropathic pain syndromes demonstrate an overexpression of N-methyl-D-aspartate-receptors in the CNS. The aim of this work was to study the influence of a central acting drug-the N-methyl-D-aspartate receptor antagonist Memantine-in patients with CRPS of one upper extremity. Here we present the results of 6 patients treated with Memantine for 8 weeks. METHODS: All patients developed CRPS after traumatic injury to one upper extremity. To document changes during the study, levels of pain were measured after clenching the hand using a numeric pain intensity scale ranging from 0 (no pain) to 10 (maximum pain). Motor symptoms were documented for the fingers (fingertips to palm and fingernails to table) and the wrist (flexion/extension). Furthermore, the force was analyzed using a JAMAR-Dynamometer and a Pinchmeter. For assessment of central changes, functional magnetic resonance imaging and magnetoencephalography were used to further document the results of other experiments in 1 patient. Autonomic changes were photographed and pictures were compared before and after treatment with Memantine. RESULTS: Six months after treatment with Memantine, all patients showed a significant decrease in their levels of pain which coincided with an improvement in motor symptoms and autonomic changes. The functional magnetic resonance imaging and magnetoencephalography results provided evidence of cortical reorganization [changes in somatotopic maps in the primary somatosensory cortex (S1)]. These changes returned to a cortical pattern comparable to the unaffected side after treatment with Memantine. DISCUSSION: Based on these first results, the use of Memantine for treatment of CRPS seems promising and supports the hypothesis of a CNS contribution to the pathogenesis and maintenance of neuropathic pain syndromes.

[Ventilator-associated pneumonia and multiresistant bacteria]. / Beatmungsassoziierte Pneumonie und multiresistente bakterielle Erreger.

Ventilator-associated pneumonia remains the most serious nosocomial infection in critically ill patients. Providing appropriate antibiotic therapy promptly is crucial for successful treatment; whereas the diagnostic approach seems to play a minor role. The empirical antibiotic therapy should be guided by the risk for infections due to multiresistant bacteria. For patients at risk a combination therapy, considering local resistance data and formerly applied antibiotic substances, is recommended. Reevaluation and deescalation of antibiotic therapy based on microbiological culture results and discontinuation of antimicrobial treatment after one week is essential for the control of broadspectrum antibiotic use and antibiotic resistance.

Effects of long-term routine use of selective digestive decontamination on antimicrobial resistance.

OBJECTIVE: To assess the distribution of bacterial species and antimicrobial resistance in an ICU during long-term use of selective digestive decontamination (SDD) in the context of national reference data. DESIGN AND SETTING: Five-year prospective observational study in a 24-bed interdisciplinary surgical ICU of a university hospital (study ICU) participating in the project "Surveillance of Antimicrobial Use and Antimicrobial Resistance in German Intensive Care Units" (SARI; reference ICUs). PATIENTS: Resistance data were obtained from all patients; patients intubated for at least 2 days received SDD (colistin, tobramycin, amphotericin B). INTERVENTIONS AND MEASUREMENTS: SDD was performed in 1,913 of 7,270 patients. Antimicrobial resistance was examined in 4,597 (study ICU) and 46,346 (reference ICUs) isolates. RESULTS: Methicillin-resistant Staphylococcus aureus (MRSA) remained stable (2.76 and 2.58 isolates/1000 patient days) in the study ICU; this was below the German average (4.26 isolates/1000 patient days). Aminoglycoside- and betalactam-resistant Gram-negative rods did not increase during SDD use. Aminoglycoside resistance of Pseudomonas aeruginosa was 50% below the mean value of SARI (0.24 vs. 0.52 isolates/1,000 patient days). The relative frequency of enterococci and coagulase-negative staphylococci (CNS) was higher than in the SARI ICUs (23.2% vs. 17.3%, and 25.0% vs. 20.6%, respectively). CONCLUSION: Routine 5-year-use of SDD was not associated with increased antimicrobial resistance in our ICU with low baseline resistance rates. Vigorous surveillance and control measures to search and destroy MRSA were considered a mandatory component of the SDD program. The relative increase in enterococci and CNS is of concern requiring further investigation.

Influence of fluid resuscitation on renal microvascular PO2 in a normotensive rat model of endotoxemia.

INTRODUCTION: Septic renal failure is often seen in the intensive care unit but its pathogenesis is only partly understood. This study, performed in a normotensive rat model of endotoxemia, tests the hypotheses that endotoxemia impairs renal microvascular PO2 (microPO2) and oxygen consumption (VO2,ren), that endotoxemia is associated with a diminished kidney function, that fluid resuscitation can restore microPO2, VO2,ren and kidney function, and that colloids are more effective than crystalloids. METHODS: Male Wistar rats received a one-hour intravenous infusion of lipopolysaccharide, followed by resuscitation with HES130/0.4 (Voluven), HES200/0.5 (HES-STERIL 6%) or Ringer's lactate. The renal microPO2 in the cortex and medulla and the renal venous PO2 were measured by a recently published phosphorescence lifetime technique. RESULTS: Endotoxemia induced a reduction in renal blood flow and anuria, while the renal microPO2 and VO2,ren remained relatively unchanged. Resuscitation restored renal blood flow, renal oxygen delivery and kidney function to baseline values, and was associated with oxygen redistribution showing different patterns for the different compounds used. HES200/0.5 and Ringer's lactate increased the VO2,ren, in contrast to HES130/0.4. CONCLUSION: The loss of kidney function during endotoxemia could not be explained by an oxygen deficiency. Renal oxygen redistribution could for the first time be demonstrated during fluid resuscitation. HES130/0.4 had no influence on the VO2,ren and restored renal function with the least increase in the amount of renal work.

Effect of synthetic colloids on major histocompatibility complex class II expression.

STUDY OBJECTIVE: Synthetic colloids are used for perioperative fluid management. We hypothesized that their use may be associated with changes in major histocompatibility complex (MHC) class II expression. This could affect patients' morbidity and mortality during clinical intervention. SETTING: University research laboratory. SUBJECTS: Whole blood samples from healthy volunteers. INTERVENTIONS: Whole blood samples from healthy volunteers (n = 6) were incubated with different concentrations of hydroxyethyl starch (HES) from maize and potato (pHES), dextran, and polygelin (gelatine) for 24 hours with or without 100 U/mL human interferon gamma (IFN-gamma; stimulus for MHC class II expression). The expression of human leukocyte antigen (HLA): HLA-DR, HLA-DQ, and HLA-DP was detected simultaneously by a fluoresceinisothiocyanate (FITC)-labeled antibody and analyzed by flow cytometry on lymphocytes and monocytes. MEASUREMENTS AND MAIN RESULTS: Hydroxyethyl starch, pHES, and dextran induced a significant increase in HLA expression. The induction of MHC class II was independent of the structure (50 mg/mL: control, 8.7+/-1.4%; HES, 28 +/- 9.7%; pHES, 29.8 +/- 11.7%; and dextran, 50.2 +/- 8.1%). In contrast, polygelin increased HLA expression only at the highest concentration of gelatine (5 mg/mL, 7.8 +/- 1%; 50 mg/mL, 7.6 +/- 0.8%; 100 mg/mL, 7.3 +/- 1%; 200 mg/mL,16.2 +/- 2.3%). The addition of IFN-gamma decreased HLA expression in presence of highest concentration of HES and dextran. CONCLUSION: In an ex vivo laboratory setting, we demonstrate that high concentrations of plasma expanders are associated with increased HLA expression on lymphocytes and monocytes. However, further in vivo studies are necessary to demonstrate the clinical significance of this observation.