Countertransference in the treatment of patients with personality disorders: A longitudinal study.

OBJECTIVE: This study examines how therapist emotional response/countertransference (CT) develops during treatment for patients with personality disorders (PDs) and how pre-treatment patient factors (severity of personality pathology, PD category, level of symptom distress) predict CT responses. Secondly, we explored associations between patient clinical outcome and CT. METHOD: A longitudinal, observational study including 1956 patients with personality pathology treated at psychotherapy units within specialist mental health services. Therapists' emotional response was repeatedly assessed by the Feeling Word Checklist-Brief Version (FWC-BV) with three subscales-Inadequate, Confident, and Idealized. RESULTS: Levels of Inadequate CT were lowest and stable over time while Confident and Idealized increased over time. Greater severity of personality pathology and borderline PD predicted higher initial Inadequate, lower initial Confident and decreasing Inadequate over time. Antisocial PD predicted decreasing Confident. Number of PD criteria had higher impact on therapist CT than level of symptom distress. Clinical improvement was associated with decreasing Inadequate. CONCLUSION: Therapists reported predominantly Confident CT when working with PD patients. More severe personality pathology, and borderline PD, specifically, predicted more negative CT initially, but the negative CT decreased over time. Patients who did not improve were associated with increasing Inadequate.

Hyphae fragments from A. fumigatus sensitize lung cells to silica particles (Min-U-Sil): Increased release of IL-1ß.

Exposure to particulate matter (PM), such as mineral particles and biological particles/components may be linked to aggravation of respiratory diseases, including asthma. Here we report that exposure to Aspergillus fumigatus hyphae fragments (AFH) and lipopolysaccharide (LPS) induced both mRNA synthesis and release of pro-inflammatory interleukin-1 beta (IL-1ß) in both human THP-1 monocytes (THP-1 Mo) and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 monocytes (THP-1 macrophages; THP-1 Ma); while Min-U-Sil alone enhanced the release of IL-1ß only in THP-1 Ma. Co-exposure to LPS or AFH with Min-U-Sil caused a synergistic release of IL-1ß when compared to single exposures. In contrast, Min-U-Sil did not markedly change LPS- and AFH-induced release of tumor necrosis factor alpha (TNF-α). The combined exposures did not increase the LPS- and AFH-induced expression of IL-1ß mRNA. Notably, the AFH- and LPS-induced IL-1ß responses with and without co-exposure to Min-U-Sil in THP-1 Mo were found to be caspase-dependent as shown by inhibition with zYVAD-fmk. Furthermore, co-exposure with AFH and Min-U-Sil resulted in similar synergistic releases of IL-1ß in primary human airway macrophages (AM; sputum), peripheral blood monocyte-derived macrophages (MDM) and in the human bronchial epithelial cell line (BEAS-2B). In conclusion, AFH induce both the synthesis and release of IL-1ß. However, Min-U-Sil further enhanced the cleavage of the induced pro-IL-1ß.

Anticoagulant effects of an antidiabetic drug on monocytes in vitro.

INTRODUCTION: Monocyte- and microparticle (MP)-associated tissue factor (TF) is upregulated in diabetes. Lipopolysaccharide (LPS) induces expression of TF and alternatively spliced TF (asTF) and increases MP release from monocytes. Using LPS-stimulated TF-bearing human monocytes, we examined whether glibenclamide, a sulfonylurea used to treat diabetes type 2, might possess anticoagulant properties. METHODS: We studied the effects of glibenclamide on cell- and supernatant-associated procoagulant activity (Factor Xa-generating assay and clot formation assay), on expression of TF and asTF (flow cytometry, RT-qPCR, western blot) and on cell viability and MP release (flow cytometry). RESULTS: Glibenclamide dose-dependently decreased procoagulant activity of cells and supernatants. The reduction in cellular procoagulant activity coincided with reduced expression of TF and asTF in cells, whereas cell viability remained almost unchanged. The glibenclamide-induced reduction in procoagulant activity of supernatants appeared to be associated with a decreased number of released MPs. CONCLUSIONS: Reduction of monocyte- and supernatant-associated procoagulant activity by glibenclamide is associated with decreased expression of TF and asTF and possibly with a reduced MP number. Our data indicate that glibenclamide reduces the prothrombotic state in LPS-stimulated monocytes in vitro. Glibenclamide might therefore also have an anticoagulant effect in vivo, but this needs to be further evaluated.

Circulating lipopolysaccharides in the blood from "bioprotein" production workers.

BACKGROUND: Workers producing bacterial single-cell protein (BSCP), "bioprotein," are exposed to organic dust containing high levels of endoxins (lipopolysaccharides, LPS). Workers in this industry have complained of episodes of fever, fatigue, chest tightness, skin dryness and rubor. The aim of the present study was to quantify LPS and inflammatory mediators in plasma among the workers and non-exposed control subjects. METHODS: We included eight non-smoking production workers, aged 32-51 (median 38), and eight non-smoking, non-exposed controls, aged 30-51 (median 39). Airborne and plasma endotoxin concentrations were measured, as well as plasma hsCRP and different cytokines, chemokines and metalloproteinases. RESULTS: The workers who did not use personal respiratory protection were exposed to varying airborne levels of endotoxin, 430 (75-15 000) EU/m3 (median, range). The level of plasma LPS was significantly elevated (p = 0.01) among the workers compared to the non-exposed controls. The workers also had elevated levels of MCP-1 (p = 0.02), MIP-1alpha (p = 0.05) and MMP-3 (p = 0.04). IL-6 and hsCRP were also elevated among the exposed group, but not significantly (p = 0.10 and p = 0.07, respectively). CONCLUSIONS: In this study, we detected LPS in plasma of individuals exposed to high levels of LPS at their workplace. This finding is supported by elevated levels of several inflammatory cytokines among the workers, significantly exceeding that of the non-exposed control group. To the best of our knowledge, this is the first time that plasma LPS, together with increased inflammatory markers in plasma, has been detected in an occupational setting.

Tumour necrosis factor alpha and its promoter polymorphisms' role in the phenotypic expression of hemochromatosis.

BACKGROUND: The majority of hemochromatosis patients are homozygous for the HFE-C282Y mutation. However, less than half of C282Y homozygous subjects identified by population screening studies actually develop the disease. The cytokine TNF-alpha is implicated in the regulation of iron metabolism at different levels. Our aim was to study the role of TNF-alpha and its promoter polymorphisms in the phenotypic expression of hemochromatosis in individuals with and without the C282Y mutation. METHODS: We studied 4 groups of 10 subjects each: (1) C282Y homozygotes without clinical hemochromatosis; (2) C282Y homozygotes with hemochromatosis; (3) secondary hemochromatosis (without C282Y mutation); and (4) controls. Groups were age-matched and sex-matched. Peripheral blood mononuclear cells (PBMC) were stimulated with lipopolysaccharide (LPS) and the release of TNF-alpha was measured. Additionally, the G/A polymorphisms at position -238 and -308 of the TNF-alpha, gene were determined by PCR and RFLP analysis in 178 hemochromatosis patients and 41 controls. RESULTS: TNF-alpha production from PBMC at 8 and 24 h after increasing concentrations of LPS stimulation were similar in the four groups. The prevalence of TNF-alpha polymorphisms was similar in patients and controls. The prevalences of cirrhosis, siderosis, median s-ferritin and median ALT values were similar in patients with and without the TNF-alpha polymorphisms. CONCLUSIONS: Neither TNF-alpha, released from PBMC nor the presence of TNF-alpha polymorphisms seem to be associated with disease manifestation in hemochromatosis.

Neisseria meningitidis lipopolysaccharides in human pathology.

Neisseria meningitidis causes meningitis, fulminant septicemia or mild meningococcemia attacking mainly children and young adults. Lipopolysaccharides (LPS) consist of a symmetrical hexa-acyl lipid A and a short oligosaccharide chain and are classified in 11 immunotypes. Lipid A is the primary toxic component of N. meningitidis. LPS levels in plasma and cerebrospinal fluid as determined by Limulus amebocyte lysate (LAL) assay are quantitatively closely associated with inflammatory mediators, clinical symptoms, and outcome. Patients with persistent septic shock, multiple organ failure, and severe coagulopathy reveal extraordinarily high levels of LPS in plasma. The cytokine production is compartmentalized to either the circulation or to the subarachnoid space. Mortality related to shock increases from 0% to > 80% with a 10-fold increase of plasma LPS from 10 to 100 endotoxin units/ml. Hemorrhagic skin lesions and thrombosis are caused by up-regulation of tissue factor which induces coagulation, and by inhibition of fibrinolysis by plasminogen activator inhibitor 1 (PAI-1). Effective antibiotic treatment results in a rapid decline of plasma LPS (half-life 1-3 h) and cytokines, and reduced generation of thrombin, and PAI-1. Early antibiotic treatment is mandatory. Three intervention trials to block lipid A have not significantly reduced the mortality of meningococcal septicemia.

Flow cytometric evaluation of apoptosis, necrosis and recovery when culturing monocytes.

After developing and applying a method for cryopreserving monocytes, we found a substantial cell loss when culturing these cells. Monocytes were isolated from blood donors by density gradient centrifugation, purified by elutriation and cryopreserved. Thawed cells were cultured in ultra low attachment wells and studied with Annexin V, Propidium iodide, Dihexyloxacarbocyanine (DiOC(6)(3)), bromolated deoxyuridine triphosphate nucleotides (Br-dUTP), DNA ploidy and DNA ladder methodologies. The main cell loss was within the first 24 h and recovery on day 7 was 35-40%. The first 2-6 h of culture were found to be crucial for determining which cells survive. Initially (2-4 h), apoptosis was the main feature but after 6 h, necrosis dominated. Two populations of cells developed after 24 h: "A" consisting of larger cells with low levels of apoptosis and necrosis signals and population "B" comprising smaller cells with a high expression of necrotic but low levels of apoptotic signals. Signs of DNA fragmentation were slight. These early, dynamic changes may be important for the interpretation of experimental results when investigating monocytes in culture.

Non-mannose-capped lipoarabinomannan stimulates human peripheral monocytes to expression of the "early immediate genes" tissue factor and tumor necrosis factor-alpha.

In the present study, we have shown that stimulation of cryopreserved, human peripheral blood monocytes with the cell wall components from Gram-negative bacteria, lipopolysaccharide (LPS), and from rapid-growing Mycobacterium sp., non-mannose-capped lipoarabinomannan (AraLAM), both induce expression of the "early immediate genes" tissue factor (TF) and tumor necrosis factor-alpha (TNF-alpha). This was demonstrated both at the protein and the mRNA levels. Antibodies against the CD14 receptor could block the stimulating effects. AraLAM was a significantly weaker inducer than LPS, and we speculate that this may reside in the number of the fatty acids in the part of the molecule that interacts with the CD14/Toll-like receptors (TLR). Finally, both LPS and AraLAM activated the "early immediate genes" through translocation of the transcription factor proteins NF-kappaB/Rel and increasing the binding activity of AP-1.

Quantitative detection of bacterial lipopolysaccharides in clinical specimens.

Lipopolysaccharides (LPS) located to the outer leaflet of the outer membrane have been identified as the main common endotoxic component of Gramnegative bacteria (1-3). Although other constituents of the bacterial cell wall, i.e., peptidoglycan, may contribute, LPS is considered to be the single most important constituent of Neisseria meningitidis that induces inflammation in the host (4-12). Neisserial lipopolysaccharides are often referred to as lipooligosaccharides (LOS) owing to the short polysaccharide chains comprising approx 10 sugars or less that are attached to lipid A.

Isolation of monocytes from whole blood by density gradient centrifugation and counter-current elutriation followed by cryopreservation: six years' experience.

BACKGROUND: Monocyte purification by means of counter-current elutriation and subsequent cryopreservation for future use was initiated in 1986 and has been established as a routine since 1993. AIM: To sum up and evaluate our method for the isolation and preservation of monocytes. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from healthy donor blood by density gradient centrifugation, and monocytes were isolated from the PBMC by counter-current elutriation centrifugation using the Beckman J-6M/E centrifuge. The monocytes were then cryopreserved at 135 degrees C and thawed when required for experimental use. RESULTS: Results are given for the last 6 years, including 59 elutriations and the fractions containing monocytes. The mean purity of monocytes was 93% (range 64-98%); mean recovery was 51% (range 22-55%). Studies of CD14 expression and Annexin V indicate that there are no differences between elutriated fractions immediately upon purification or after freezing and thawing. The studies also indicate that interdonor variations are much larger than intradonor variations. DISCUSSION: Although it differs from other reports in certain respects, our procedure has nevertheless produced results in line with other findings. After extensive testing and use in different contexts we feel confident that we have established a method for producing a large number of purified and well-preserved monocytes. CONCLUSION: The goal of being able to perform a large number of experiments with monocytes of high purity and good functionality has been reached.

Aspirin potentiates LPS-induced fibrin formation (FPA) and TNF-alpha-synthesis in whole blood.

The effect of aspirin on LPS-incubation of whole blood was investigated. Aspirin induced a concentration dependent increase (2.5-5-fold at 5 mM aspirin) in LPS-induced appearance of TNF-alpha and fibrinopeptide A (FPA) in plasma, despite the concomitant increase in the inhibitory cytokine IL-100. Aspirin substantially raised the levels of LPS-induced TF-mRNA and TNFalpha-mRNA in monocytes isolated from whole blood. The median ratio for TF-/beta-actin mRNA increased from 1.5 +/- 0.44 in the presence of LPS-alone, to 2.5 +/- 0.51 when 5 mM aspirin was added. The TNFalpha/beta-actin mRNA ratios were 1.8 +/- 0.4 and 5.5 +/- 2.7 respectively. Addition of exogenous PGE2 before incubation nearly abrogated the effect of aspirin on TNF-alpha, substantiating the role of PGE2 as a regulator of TNF-alpha synthesis, whereas the effect on FPA was small. Thus, in the presence of LPS in this whole blood model, aspirin apparently had a pro-inflammatory rather than an anti-inflammatory effect.

Fulminant meningococcal septicemia: dissociation between plasma thrombopoietin levels and platelet counts.

Thrombopoietin (TPO), interleukin (IL)-6, and platelets were measured serially in 9 patients with fulminant meningococcal septicemia and consumption coagulopathy. The results were compared with those of patients with meningococcal meningitis and mild meningococcemia (n=10) and with those of healthy control subjects (n=19). TPO levels in control subjects were below the detection limit (<63 pg/mL). In patients with fulminant meningococcal septicemia, the median TPO level on admission was 193 pg/mL (range, 133-401 pg/mL), and the level peaked within 3-7 days (median, 488 pg/mL; range, 239-1334 pg/mL). Platelet counts remained low, despite the elevated TPO levels. In patients with meningitis or meningococcemia, the median TPO level on admission was 112 pg/mL (range, <63-695 pg/mL), and the TPO level was not detectable within 48 h. Platelet counts for these patients remained within normal limits. Maximum IL-6 levels in patients with septicemia were observed on admission (median, 5317 pg/mL; range, 188-651,000 pg/mL) and increased earlier than TPO levels. In patients with fulminant septicemia, TPO level increases significantly whereas the level of circulating platelets does not.

Cellular activating properties and morphology of membrane-bound and purified meningococcal lipopolysaccharide.

Neisseria meningitidis, the cause of epidemic meningitis and acute lethal sepsis, synthesizes surplus lipopolysaccharides (LPSs) during growth, which are released as outer membrane vesicles (OMV) or "blebs". Meningococcal disease severity is related to plasma LPS levels. We have compared the biological activities of native outer membrane vesicles (nOMV) to those of purified Nm-LPS (Nm-LPS) and LPS-depleted OMV (dOMV) prepared from N. meningitidis. The LPS content of nOMV was determined spectrophotometrically by quantifying KDO and by silver-stained SDS-PAGE gels. The morphology of the preparations was studied by transmission electron microscopy. The Limulus amoebocyte lysate (LAL) assay was used to quantify LPS in the plasma solutions. The preparations were diluted in endotoxin-free heparin plasma to equal amounts of LPS (w/w) in the range 50-5000 pg/ml. The biological reactivity was tested by: (i) a monocyte target-assay (monocyte purity > or =96%); and (ii) a whole blood model, measuring the secretion of TNF-alpha and IL-6 induction of procoagulant activity in monocytes (PCA). In both models, nOMV induced dose-dependent cell responses (TNF-alpha, IL-6, PCA) similar to purified Nm-LPS, whereas dOMV induced minimal responses. However, LAL activity was significantly higher for nOMV than for purified Nm-LPS and dOMV. The cellular responses of purified Nm-LPS and nOMV were reduced (>95%) by a specific anti-CD14-antibody.

Acetylsalicylic acid and sodium salicylate inhibit LPS-induced NF-kappa B/c-Rel nuclear translocation, and synthesis of tissue factor (TF) and tumor necrosis factor alfa (TNF-alpha) in human monocytes.

We have investigated the effects of acetylsalicylic acid and sodium salicylate on the LPS-induced synthesis of the pro-coagulant protein tissue factor (TF) and the pro-inflammatory protein tumor necrosis factor-alpha (TNF-alpha), as well as the prostaglandin PGE2 in human monocytes. Both drugs dose-dependently inhibited LPS-induced TF and TNF-alpha synthesis at the mRNA and the protein level, and reduced PGE2 production. As evidenced by electro mobility shift assay (EMSA) and the use of a NF-kappa B prototypic probe, these drugs probably exert their inhibitory effects by interference with the nuclear translocation of NF-kappa B/c-Rel proteins. These data may expand the understanding of the anti-thrombotic and anti-inflammatory effects of these drugs when activation of monocytes occurs.

Net inflammatory capacity of human septic shock plasma evaluated by a monocyte-based target cell assay: identification of interleukin-10 as a major functional deactivator of human monocytes.

We have developed a functional assay to study the inflammatory capacity of plasma collected from patients with severe gram-negative septic shock. In this assay, elutriation-purified, cryo-preserved human monocytes from one healthy donor are combined with plasma from patients with severe persistent septic shock for 5 h. Subsequently, the plasma is removed, medium added, and procoagulant activity (PCA) and secretion of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) measured after 18-h incubation. Plasma from 10 patients (6 died) infected with Neisseria meningitidis previously shown to contain high levels of native lipopolysaccharide (LPS) (median 2,700 pg/ml), TNF-alpha, IL-6, IL-8, and complement activation products, had a low net spontaneous inflammatory capacity on the monocytes. The median levels of PCA, TNF-alpha, and IL-6 were 5, 0, and 4%, respectively, of the monocyte activities induced by normal plasma boosted with purified N. meningitidis (Nm)-LPS (2,500 pg/ml; net LPS-boosted capacity, 100%). The levels of PCA, TNF-alpha, and IL-6 obtained with plasma from shock patients were not different from those induced by plasma from 10 meningococcal patients without shock or with plasma from healthy persons. Boosting shock plasma with 2,500 pg/ml Nm-LPS had little effect on the monocyte activities since the median values of PCA, TNF-alpha, and IL-6 revealed a minimal increase from 5, 0, and 4% to 9, 2, and 6%, respectively. The shock plasmas revealed a strong LPS-inhibitory capacity that was largely absent in plasmas from 10 meningococcal patients without shock since the median levels of PCA, TNF-alpha, and IL-6 increased from 5, 0, and 0% to 135, 51, and 73%, respectively, after boosting with 2,500 pg/ml Nm-LPS. The LPS-inhibitory capacity was closely associated with the levels of IL-10. The median levels of IL-10 were 19,000 pg/ml in nine shock patients vs. 22 pg/ml in nine nonshock patients with systemic meningococcal disease. Removal of native IL-10 by immunoprecipitation restored the capacity of plasmas to induce monocyte activation either by native LPS or by boosting with Nm-LPS. IL-4 and TGF-beta were not detected in shock plasmas. In 24 patients with detectable meningococcal LPS ( > 10 pg/ml, 0.1 endotoxin units/ml), the levels of IL-10 were correlated to the levels of LPS (r = 0.79, P < 0.001). IL-10 declined from initiation of antibiotic therapy and paralleled the levels of native LPS. Decreasing levels of IL-10 in serially collected shock plasmas were directly related to increasing monocyte responsiveness after Nm-LPS boosting. These results suggest that IL-10 plays a major role in containing activation of monocytes and possibly other LPS-responsive cells during overwhelming meningococcemia.

LPS-induced release of EGF, GM-CSF, GRO alpha, LIF, MIP-1 alpha and PDGF-AB in PBMC from persons with high or low levels of HDL lipoprotein.

We have examined basal and lipopolysaccharide (LPS)-induced release of epidermal growth factor (EGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), growth-regulated peptide alpha (GRO alpha), leukaemia inhibitory factor (LIF), macrophage inflammatory protein-1a (MIP-1 alpha) and platelet-derived growth factor-AB (PDGF-AB) in peripheral blood mononuclear cells (PBMC) from 20 persons with either high (n = 10) or low (n = 10) levels of high-density lipoprotein (HDL). PBMC were incubated with 100 ng LPS/ml for up to 160 h, and showed a significantly higher release of the chemokines GRO alpha (P = 0.04) and MIP-1 alpha (P < 0.01) in persons with high HDL, whereas levels of GM-CSF were similar. Levels of EGF, LIF and PDGF-AB were always low, and remained unaltered during 160 h of incubation. These findings indicate that PBMC from persons with high or low levels of HDL have different functional properties, of importance in cell recruitment and activation.

LPS induced procoagulant activity and plasminogen activator activity in mononuclear cells from persons with high or low levels of HDL lipoprotein.

UNLABELLED: We have examined spontaneous and lipopolysaccharide (LPS) induced procoagulant activity (PCA) and plasminogen activator activity (PA) in peripheral blood mononuclear cells (PBMC) from ten persons with high, and ten persons with low levels of serum high-density lipoprotein (HDL). PBMC were incubated +/- 100 ng LPS/ml up to 160 h. Additionally, we have measured the release of urokinase (uPA), tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1) and plasminogen activator inhibitor 2 (PAI-2) into the cell culture media. Spontaneous PA was significantly higher in PBMC from persons with low HDL, combined with lower release of uPA to the media and higher uPA-receptor (uPA-R) bound uPA on PBMC. Upon stimulation with LPS, PCA and released PAI-2 increased sharply, while PA and released uPA declined. These changes were not significantly different between the two groups. tPA and PAI-1 were not detected in cell lysates or in cell culture media. CONCLUSIONS: 1) LPS sharply stimulated PBMC PCA (similar in both groups). 2) PBMC from persons with low HDL showed higher spontaneous PA, due to higher uPA-R bound uPA, probably of importance in cell migration during the early events of atherosclerosis.

The development of femoral osteopenia in ovariectomized rats is not reduced by high intensity treadmill training: a mechanical and densitometric study.

The effect of treadmill running on the development of osteopenia was investigated in adult ovariectomized (OVX) rats compared with sedentary OVX and sedentary sham-operated rats. The rats were 3 months old with a mean weight of 214 g. OVX rats were fed a low calcium diet (0.01%), and the sham rats received the normal diet (1.1% calcium). The training consisted of treadmill running at a speed of 27 m/minute for 1 hour 5 out of 7 days during a period of 8 1/2 weeks. The weight gain was higher in the sedentary OVX (108 g) than in the training OVX (62 g) and sham-operated rats (61 g) (P < 0.001). Comparing the two OVX groups, training had no significant effects on the development of femoral osteopenia as assessed by mechanical testing of the femoral shaft and neck, and by bone mass measurements by dual energy X-ray absorptiometry (DXA) or by ashing. Comparing all three groups bone mineral content (BMC) and bone mineral density (BMD) were reduced by more than 40% in both the OVX groups compared with the sham-operated rats (P < 0.001). Ash weight and calcium content were reduced by approximately 40% in both OVX groups. Femoral volume and length were 10% higher in the sedentary OVX animals compared with the trained (P < 0.05), indicating that the training had had a negative effect on the growth changes induced by ovariectomy. The fracture strength of the femoral shaft was reduced by 26% and 22% in the trained and sedentary OVX rats, respectively compared with the sham-operated group (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

LPS-induced release of IL-1 beta, IL-6, IL-8, TNF-alpha and sCD14 in whole blood and PBMC from persons with high or low levels of HDL-lipoprotein.

We have examined basal and lipopolysaccharide (LPS)-induced release of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrosis factor-alpha (TNF-alpha) and soluble CD14 (sCD14) in whole blood and peripheral blood mononuclear cells (PBMC) from 20 persons with either high (1.62-2.47 mmol/L) or low (0.43-1.29 mmol/L) levels of high-density lipoprotein (HDL). Whole blood was incubated at 37 degrees C for 2 h with 100 ng LPS/ml, while PBMC were incubated with 100 ng LPS/ml for up to 160 h. The LPS-induced release of IL-1 beta, IL-6, IL-8 and TNF-alpha into plasma showed no differences between the two HDL-groups; whereas levels of sCD14 were significantly higher in plasma in persons with low HDL (P < 0.01). PBMC incubated with LPS showed a significantly higher release of IL-1 beta (P = 0.01) and IL-6 (P = 0.02) in persons with high HDL at all sampling times. sCD14 was found not to be released by PBMC. These findings indicate that PBMC from persons with high or low levels of HDL have different functional properties, possibly of importance in inflammation and atherogenesis.