Biomedical subjects

M Herold

Publications and source records attributed to M Herold.

At least 37 records · Page 2Linked to original sources

PubMed2001

Production of IL-12 by human monocyte-derived dendritic cells is optimal when the stimulus is given at the onset of maturation, and is further enhanced by IL-4.

Dendritic cells produce IL-12 both in response to microbial stimuli and to T cells, and can thus skew T cell reactivity toward a Th1 pattern. We investigated the capacity of dendritic cells to elaborate IL-12 with special regard to their state of maturation, different maturation stimuli, and its regulation by Th1/Th2-influencing cytokines. Monocyte-derived dendritic cells were generated with GM-CSF and IL-4 for 7 days, followed by another 3 days +/- monocyte-conditioned media, yielding mature (CD83(+)/dendritic cell-lysosome-associated membrane glycoprotein(+)) and immature (CD83(-)/dendritic cell-lysosome-associated membrane glycoprotein(-)) dendritic cells. These dendritic cells were stimulated for another 48 h, and IL-12 p70 was measured by ELISA. We found the following: 1) Immature dendritic cells stimulated with CD154/CD40 ligand or bacteria (both of which concurrently also induced maturation) secreted always more IL-12 than already mature dendritic cells. Mature CD154-stimulated dendritic cells still made significant levels (up to 4 ng/ml). 2) Terminally mature skin-derived dendritic cells did not make any IL-12 in response to these stimuli. 3) Appropriate maturation stimuli are required for IL-12 production: CD40 ligation and bacteria are sufficient; monocyte-conditioned media are not. 4) Unexpectedly, IL-4 markedly increased the amount of IL-12 produced by both immature and mature dendritic cells, when present during stimulation. 5) IL-10 inhibited the production of IL-12. Our results, employing a cell culture system that is now being widely used in immunotherapy, extend prior data that IL-12 is produced most abundantly by dendritic cells that are beginning to respond to maturation stimuli. Surprisingly, IL-12 is only elicited by select maturation stimuli, but can be markedly enhanced by the addition of the Th2 cytokine, IL-4.

Adjuvants, Immunologic↗

PubMed2001

Circadian and infradian rhythms in mood.

The aim of this study was to assess any variation in positive, negative and total affect recorded longitudinally; to compare the results with those from prior transverse or hybrid population studies, based on the same or a different method of mood rating; and to test for any association of mood with cardiovascular, hormonal and geophysical variables monitored concomitantly. The study approach was as follows. A clinically healthy 34-year-old man filled out the positive and negative affective scale (PANAS) questionnaire five times a day for 86 days. Systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR) were also measured automatically at 30-minute intervals with an ambulatory monitor from May 19 to June 29, 2000, while different endpoints of heart rate variability (HRV) were also determined at 5-minute intervals from beat-to-beat electrocardiogram (ECG) monitoring for 42 days between May 3 and June 14, 2000, with only short interruptions while the subject took a shower and changed ECG tapes. Saliva samples were collected at the times of mood ratings for one month for later determination of melatonin and cortisol concentrations. Intervals of 24 hours of the record of each variable displaced in increments of 24 hours were analyzed by chronobiologic serial section at a trial period of 24 hours to assess the circadian characteristics as they changed from one day to another. Estimates of the midline-estimating statistic of rhythm (MESOR) and circadian amplitude and acrophase obtained on consecutive days were correlated among variables to assess any associations. The findings were as follows. Overall, a circadian rhythm was demonstrated for all variables. A positive association was noteworthy between the circadian amplitude of negative affect and the MESOR of both SBP (r= 0.363; P= 0.029) and DBP (r= 0.389; P= 0.019), suggesting that BP is raised in the presence of large swings in negative affect. Needing further validation was a weak association between the MESOR of negative affect and the circadian amplitude of SBP (r= - 0.272; P = 0.108), suggesting a lowering of the circadian SBP amplitude in the presence of a strong negative affect. Of further interest was the lack of a statistically significant relation between positive and negative affect, not only in terms of the MESOR but also in terms of the circadian amplitude.

Adult↗

PubMed2001

Hyperhomocysteinemia in bodybuilders taking anabolic steroids.

Background: Hyperhomocysteinemia has been accepted as an independent risk factor for atherosclerosis and atherothrombosis. In recent years, several reports have appeared in the literature linking the use of anabolic steroids with acute vascular events in bodybuilders. In this study, we investigated whether hyperhomocysteinemia could contribute to the high vascular risk in bodybuilders taking anabolic steroids. Methods and results: Twenty-three bodybuilders in different phases of their training cycle and six control athletes participated in our study. Anthropomorphic measures displayed a higher body mass index for bodybuilders in the competition phase than for bodybuilders in the work-out and build-up phases, and for control athletes. Homocysteine levels were 8.7+/-1.6 µmol/l (mean+/-S.D.) in control athletes, 8.5+/-2.8 µmol/l in work-out phase bodybuilders, and 8.3+/-1.5 µmol/l in competition phase bodybuilders, but 11.9+/-3.1 µmol/l in build-up phase bodybuilders (P<0.05 for build-up phase bodybuilders vs. control athletes, work-out phase bodybuilders, and competition phase bodybuilders, respectively). Vitamin B12 and folate levels did not differ significantly between the four groups. Conclusion: Our study shows that intake of anabolic steroids, as used typically by bodybuilders in the build-up phase, induces acute hyperhomocysteinemia and is likely to initiate an additional, potentially atherothrombotic mechanism in this group of athletes.

Journal Article↗

PubMed2001

New insecticidal rocaglamide derivatives and related compounds from Aglaia oligophylla.

Organic-soluble extracts of the twigs of Aglaia oligophylla collected in Vietnam yielded four insecticidal cyclopentatetrahydrobenzofurans of the rocaglamide type including one new natural product (compound 4). Moreover, two cyclopentatetrahydrobenzopyran derivatives, belonging to the aglain and aglaforbesin types, respectively, were also isolated. The aglaforbesin derivative 6 proved likewise to be a new natural product. All isolated rocaglamide, aglain, and aglaforbesin derivatives have a characteristic methylenedioxy substituent linked to C-6 and C-7 or to C-7 and C-8, respectively. Structure elucidation of the new natural products and the determination of the absolute configuration of compound 1 by calculation of its CD spectrum with molecular dynamics simulation are described. All isolated rocaglamide derivatives exhibited strong insecticidal activity toward neonate larvae of the polyphageous pest insect Spodoptera littoralis when incorporated into an artificial diet, with LC(50) values varying between 2.15 and 6.52 ppm.

Animals↗

PubMed2001

Plasma levels of procalcitonin and interleukin-6 in acute myocardial infarction.

Estimation of cardiac morbidity in patients after major surgery is a difficult problem. In addition, infectious complications seriously decrease potential beneficial outcome after cardiovascular surgery. The present study assessed the use of a newer marker of the inflammatory response, procalcitonin, in the field of myocardial infarction, in conjunction with measurements of interleukin-6. Forty-four consecutive cases with acute myocardial infarction were included in the study 4+/-1.3 h after the onset of symptoms. Plasma levels of procalcitonin and interleukin-6 were obtained at admission, and after 3, 6, 12, 18, 24 and 48 h, using commercially available test kits. The range of levels of interleukin-6 and procalcitonin was about normal at admission. Interleukin-6 levels increased significantly following myocardial infarction, whereas procalcitonin were essentially unchanged, i.e. remained close to the normal level threshold of 0.5 ng/ml; only minor variability occurred with a mean peak level of procalcitonin of 1+/-0.4 ng/ml. Data demonstrate that, in contrast to the acute phase reactant interleukin-6, plasma levels procalcitonin are not significantly elevated during uncomplicated acute myocardial infarction. This observation may support the role of procalcitonin measurements in the differential diagnosis of infectious and cardiovascular complications after major surgery.

Acute-Phase Reaction↗

PubMed2001

Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens.

Mobilised peripheral blood stem cells are widely used for autografting in patients with chronic myeloid leukaemia (CML) and it is generally thought that a high proportion of Ph-negative progenitor cells in the graft is desirable. We report here the results of 91 stem cell mobilisations performed with various chemotherapy regimens followed by G-CSF. We show that mobilisation of Ph-negative cells is possible after diagnosis as well as in advanced stages of the disease. The yield of Ph-negative cells is highly dependent on the chemotherapy regimen: while the combination of idarubicin and cytarabin for 3-5 days (IC3-5) mobilised Ph-negative cells in most patients, high-dose cyclophosphamide was ineffective. Mobilisation of Ph-negative progenitor cells after IC3 was at least as effective as after IC5; however, less apheresis sessions were required, and toxicity was much reduced after IC3. Compared to historical controls, IC was equally effective as the widely used ICE/miniICE (idarubicin, cytarabin, etoposide) protocol. No correlation was found between graft quality and the cytogenetic response to subsequent treatment with interferon-alpha. We conclude that IC3 is an effective and well-tolerated regimen for mobilising Ph-negative cells that compares well with more aggressive approaches such as IC5 and ICE/miniICE.

Adolescent↗

PubMed2001

Fludarabine plus cyclophosphamide is an efficient treatment for advanced chronic lymphocytic leukaemia (CLL): results of a phase II study of the German CLL Study Group.

The efficacy and toxicity of a combination of fludarabine and cyclophosphamide (FC) was evaluated in patients with B-cell chronic lymphocytic leukaemia (CLL). Between April 1997 and July 1998, 36 patients with CLL (median age 59 years) received a regimen that consisted of fludarabine 30 mg/m(2) in a 30-min IV infusion, d 1-3, and cyclophosphamide 250 mg/m(2) in a 30-min IV infusion on d 1-3. Cycles were repeated every 28 d. Twenty-one patients had received between one and three different treatment regimens prior to the study, while 15 patients had received no prior therapy. The median Eastern Cooperative Oncology Group performance score was 1. One patient was at Binet stage A, 18 were stage B and 17 patients were stage C. Objective responses, assessed according to the revised guidelines of the National Cancer Institute-sponsored Working Group, were recorded in 29 out of 32 assessable patients (90.6%). Twenty-four partial remissions and five complete remissions were observed. Two patients showed no change and one patient showed disease progression. At February 2000, three of the responders had relapsed. Severe neutropenia, anaemia and thrombocytopenia (Common Toxicity Criteria grade 3 and 4) were observed in 25, six and six patients (69.4%, 16.7% and 16.7%) respectively. Other side-effects were uncommon. No treatment-related deaths and no grade 3 or 4 infections occurred. We conclude that the combination of fludarabine and cyclophosphamide showed significant activity in patients with CLL. Myelosuppression was the major side-effect. These results warrant further study on the FC combination in randomized trials.

Adult↗

PubMed2001

[Influence of reflex zone therapy of the feet on intestinal blood flow measured by color Doppler sonography].

OBJECTIVE: An influence on organ-associated blood flow is considered as a possible mechanism of action of reflex zone massage of the feet (FRZM) therapy. In the present study we investigated whether changes in intestinal blood flow can be achieved by FRZM. MATERIAL AND METHODS: 32 healthy adults (19 women and 13 men) were randomly assigned to the treatment or the placebo group. Subjects of the treatment group received foot massage on the zones assigned to the intestines and those of the placebo group received massage on zones unrelated to the intestines. Before, during and after FRZM, the blood flow velocity, the peak systolic and the end diastolic velocities in the superior mesenteric artery as well as the resistive index as a parameter of vascular resistance were calculated. RESULTS: During FRZM, in the subjects of the treatment group there was a significant reduction in the resistive index (p = 0.021), suggesting an increase in the blood flow in the superior mesenteric artery and the subordinate vascular system. In contrast, there were no significant changes in the resistive index in the subjects of the placebo group. CONCLUSION: The reduction in the resistive index observed in the treatment group supports the assumption that FRZM improves blood flow in the organs considered to be associated with the specific foot zones, at least during the therapy process.

Adult↗

PubMed2001

Prospective controlled evaluation of the influence of an excursion to a health resort on medical students' opinion about chances for outpatient rehabilitation at a health resort.

OBJECTIVE: To assess the influence of an excursion to a health resort on students' opinion on the chances for outpatient rehabilitation at a health resort for cardiac and rheumatic diseases. METHODS: A group of 17 medical students went on a 1-day excursion to Bad Orb (near Frankfurt/M.) where mainly patients with heart diseases are treated. Another group of 44 students went on a 5-day excursion to Bad Gastein (Austria) where mainly patients with rheumatic diseases are treated. Before and after the excursion students completed a questionnaire asking their opinion on the chances for outpatient rehabilitation at a health resort for acute and chronic cardiac and rheumatic diseases. RESULTS: Students judged the chances for beneficial effects of outpatient rehabilitation at a health resort for chronic rheumatic diseases to be significantly better after the excursion to Bad Gastein than before, whereas there was no difference after the excursion to Bad Orb. CONCLUSION: Students' opinion of chances for outpatient rehabilitation at a health resort can be influenced by an excursion to a spa, but a single 1-day excursion may not be sufficient.

Adult↗

PubMed2000

Altered circadian rhythms of the stress hormone and melatonin response in lupus-prone MRL/MP-fas(Ipr) mice.

The immune system interacts with the hypothalamo-pituitary-adrenal axis via so-called glucocorticoid increasing factors, which are produced by the immune system during immune reactions, causing an elevation of systemic glucocorticoid levels that contribute to preservation of the immune reactions specificities. Previous results from our laboratory had already shown an altered immuno-neuroendocrine dialogue via the hypothalamo-pituitary-adrenal axis in autoimmune disease-prone chicken and mouse strains. In the present study, we further investigated the altered glucocorticoid response via the hypothalamo-pituitary-adrenal axis in murine lupus. We established the circadian rhythms of corticosterone, dehydroepiandrosterone-sulfate, adrenocorticotropic hormone and melatonin, as well as the time response curves after injection of interleukin-1 of the first three parameters in normal SWISS and lupus-prone MRL/MP-fas(Ipr) mice. The results show that lupus-prone MRL/ MP-fas(Ipr) mice do not react appropriately to changes of the light/dark cycle, circadian melatonin rhythms seem to uncouple from the light/dark cycle, and plasma corticosterone levels are elevated during the resting phase. Diurnal changes of dehydroepiandrosterone-sulfate and adrenocorticotropic hormone were normal compared to healthy controls. These data indicate that MRL/ MP-fas(Ipr) mice not only show an altered glucocorticoid response mediated via the hypothalamo pituitary adrenal axis to IL-1, but are also affected by disturbances of corticosterone and melatonin circadian rhythms. Our findings may have implications for intrathymic T cell development and the emergence of autoimmune disease.

Adrenal Glands↗

PubMed2000

Successful treatment and re-treatment of resistant B-cell chronic lymphocytic leukemia with the monoclonal anti-CD 20 antibody rituximab.

We report on two patients with chemoresistant B-cell chronic lymphocytic leukemia who were treated successfully with the monoclonal anti-CD 20 antibody rituximab. Both patients suffered from severe thrombocytopenia requiring platelet transfusions over a period of several months. Neither chemotherapy nor immunosuppressive agents (corticoids, immunoglobulins) were effective. After four doses of rituximab (375 mg/m2 weekly), both patients recovered within a few weeks to hematological partial remission. One patient was re-treated successfully three times after relapses. Both patients were premedicated with prednisone (100 mg) 30 min prior to the infusion to prevent cytokine release and the antibody infusions were well tolerated.

Antibodies, Monoclonal↗

PubMed2000

Interleukin-6 serum concentration in ankylosing spondylitis: a reliable predictor of disease progression in the subsequent year?

The aim of the present study was to evaluate whether in ankylosing spondylitis (AS), interleukin-6 (IL-6) is a reliable predictor of changes in mobility in the subsequent year. Of 261 AS patients who had been enrolled in a previous study, 128 returned for treatment at our health centre after 1 year (+/-3 months). The variables for mobility after 1 year (II) were compared with the findings of the previous year (I). Differences in parameters for mobility were related to the serum concentration of IL-6 in the previous year. Relation between serum concentration of IL-6 and difference (II-I) in occiput-to-wall distance (Spearman's rank correlation coefficient r(s), P value) was 0.02, 0.82; chin-chest distance -0.09, 0.31; cervical rotation -0.08, 0.39; chest expansion 0.05, 0.54; finger-floor distance -0.02, 0.84; Ott sign (flexibility of the thoracic spine) -0.11, 0.22; Schober sign 0.01, 0.94. After 1 year there was a significant improvement in cervical rotation in patients with low IL-6 serum concentration (lower quartile), but not in those with high levels of IL-6 (upper quartile). No further difference was seen between patients with high or low levels of IL-6. The present data suggest that the serum concentration of IL-6 does not allow a prediction of disease progression in the subsequent year.

Cervical Vertebrae↗

PubMed2000

Increase in immune activation, vascular endothelial growth factor and erythropoietin after an ultramarathon run at moderate altitude.

The present study was performed to investigate the effects of exhaustive long lasting exercise at moderate altitude on the time course of serum immunomodulatory peptides, vascular endothelial growth factor (VEGF) and serum erythropoietin (EPO). Thirteen well trained runners participated at the Swiss Alpine Marathon of Davos (distance 67 km, altitude difference 2300 m). Interleukin-6 was significantly elevated in the first 2h after the run. In contrast, tumor necrosis factor-alpha and both soluble tumor necrosis factor-a receptors I and II were increased after exercise termination and showed sustained serum concentrations the following days. Neopterin, a serum marker for the activation of the cellular immune system, was increased until day two after the run. Immediately after the run VEGF was significantly elevated and further increased 2.4-fold until day five post exercise (p = 0.005). EPO was also increased after exercise but reached its maximum 2 h after the run (2-fold increase; p = 0.004) and decreased thereafter. The main findings of our study are that prolonged strenuous exercise at moderate altitude induced a significant long lasting increase in serum VEGF and EPO which was accompanied by an activation of the immune system.

Adult↗

PubMed2000

Low platelet count and elevated serum thrombopoietin after severe trauma.

Platelet count is regularly low in patients after multiple trauma, mainly due to blood loss and dilution. Thrombopoietin (TPO) is the main regulator of the circulating platelet mass. Under several clinical conditions an inverse correlation between TPO and the circulating platelet mass was reported. Since platelets bind and internalize TPO, a platelet-dependent regulation of TPO was suggested. Thus, acute blood loss should be accompanied by elevated TPO. We measured serum TPO, platelets, interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in 17 multiple traumatized victims. Blood was collected within 12 h after trauma as well as in the morning of days 2, 4, 6 and 9 after admission at the intensive care unit. Platelet count was low at admission and remained low until day 4. Thereafter platelets increased until day 9. TPO nearly doubled within the first 2 d, reaching its maximum on day 6. IL-6 was initially very high and steadily decreased until day 9. VEGF increased 3-fold during the 9 d. Statistically significant correlations of TPO were found with platelets and IL-6, but not with VEGF. In multiple traumatized patients low platelet count is followed by a rapid increase in serum TPO. This fits into the concept of a feedback regulation between circulating TPO and platelet mass.

Adult↗

PubMed2000

Tumour necrosis factor-alpha plasma level in patients with type 1 diabetes mellitus and its association with glycaemic control and cardiovascular risk factors.

OBJECTIVES: Diabetic patients reveal a significant increase in their cardiovascular risk. Beside glycaemic control and management of established risk factors, determination of cytokines, like serum levels of tumour necrosis factor-alpha (TNF-alpha), might offer a tool to determine patients at high risk. The cytokine TNF-alpha reveals a complex relationship with diabetes. It is involved in beta-cell damage leading to type 1 diabetes, causes insulin resistance associated with obesity and is of influence in the formation of atherosclerotic vascular lesions. We were interested in the possible association of this cytokine with metabolic control and cardiovascular risk factors in patients with type 1 diabetes. DESIGN AND SUBJECTS: TNF-alpha plasma levels were determined in 44 outdoor patients (15 women, 29 men) with type 1 diabetes mellitus (mean duration 11.2 +/- 8.7 years) and in 24 healthy controls by use of a solid phase enzyme amplified sensitivity immunoassay (TNF-alpha ELISA, Biosource Fleurus, Belgium). None of our study participants suffered from inflammatory or other concurrent diseases. Relationships between variables were evaluated by non-parametric Spearman correlation coefficients. RESULTS: TNF-alpha plasma levels were significantly higher in diabetic patients (19.3 +/- 7.5 pg mL-1) than in non-diabetic subjects (11.1 +/- 5.8 pg mL-1; P < 0. 023), and revealed a significant positive correlation with glycated haemoglobin (HbA1c) (r = 0.43; P < 0.004) and fructosamine (r = 0. 31; P < 0.049) values, and a negative correlation with HDL cholesterol (r = -0.36; P < 0.018) and apoAI-levels (r = -0.37; P < 0.015). These relationships could be observed in patients with a duration of diabetes for more than 5 years, as well as in patients with a shorter duration of diabetes. In the male group, TNF-alpha plasma levels revealed a significant positive correlation with plasma levels of thiobarbituric acid reacting substances (r = 0.61; P < 0.001). Plasma levels of thiobarbituric acid reacting substances showed a positive correlation with the duration of diabetes (r = 0. 58; P < 0.008), as well as with the serum levels of the vascular adhesion molecules intercellular adhesion molecule (ICAM) (r = 0.34; P < 0.051) and vascular cell adhesion molecule (VCAM) (r = 0.30; P < 0.052). CONCLUSIONS: Our data indicate that TNF-alpha plasma levels are increased in type 1 diabetes mellitus and reveal a significant association with metabolic long-term control parameters, HbA1c and fructosamine for glycaemic control, and HDL cholesterol for triglyceride metabolism, as well with lipid peroxidation.

Adult↗

PubMed1999

Expression of stress proteins, adhesion molecules, and interleukin-8 in endothelial cells after preservation and reoxygenation.

Endothelial activation is a central feature of preservation-induced allograft injury. The present study aims at a quantitative assessment of stress proteins, adhesion molecules, and interleukin-8 in a cell culture-based model of organ preservation. Human umbilical vein endothelial cells were exposed to cold, hypoxic storage in University of Wisconsin (UW), histidine-tryptophane-ketoglutarate (HTK), and EuroCollins solutions for 8 h with subsequent rewarming/reoxygenation (rew/reox) for 1 and 4 h. A cell-based ELISA was designed for detection of heat shock proteins (HSP) 60 and 70, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1). Immunohistochemical staining was performed for comparison. Interleukin-8 was quantified by ELISA. HSP 70 was expressed after cold storage in HTK and EuroCollins solution and after rew/reox in all groups. A constitutive expression of HSP 60 was observed with further upregulation after rew/reox following cold storage in all experimental groups. ICAM-1 was clearly upregulated, but VCAM-1 showed only weak expression after cold storage and rew/reox. ELAM-1 was detectable in minimal amounts after cold storage but was considerably upregulated after 4 h of rew/reox. A significant increase of interleukin-8 release could be found after 4 h of rew/reox following storage in EuroCollins solution. Expression of stress proteins can be considered as a new parameter of preservation-associated endothelial activation. Apart from possible protective effects, allograft vasculopathy could be in part a consequence of the antigeneic potential of heat shock proteins connected with effects caused by adhesion molecules and inflammatory cytokines.

Adenosine↗

PubMed1999

Mediator-dependent effects of pentoxifylline on endothelium for transmigration of neutrophils.

In the present study, we investigated the effects of the anti-inflammatory drug pentoxifylline (PTX) on activation of endothelial cells for enhanced adhesion and transmigration of neutrophils by lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1) and granulocyte colony-stimulating factor (G-CSF). To evaluate the mechanism by which PTX exerts its effect, human umbilical vein endothelial cells (HUVEC) were pretreated with theophylline, 2'-O-dibutyryl-3', 5'-cyclic adenosine monophosphate (db cAMP), and 3-isobutyl-1-methylxanthine, respectively, prior to stimulation. Pretreatment of HUVEC with PTX significantly antagonized TNF-, IL-1-, and G-CSF-activated transmigration of neutrophils. Additive stimulatory effects of PTX were seen with LPS. With the exception of theophylline, all other test cAMP-raising agents stimulated transmigration in similar fashion to PTX. Upon stimulation with TNF or LPS, HUVEC produced IL-8 and PTX affected this process in opposing fashions, with inhibition of the effects of TNF and augmentation of those of LPS. These results demonstrate that PTX differentially affects mediator-induced activation of HUVEC. The present IL-8 dependent and cAMP-regulated augmentation of LPS-induced stimulation of transmigration is the first description of an additive effect of PTX with a pro-inflammatory agent.

1-Methyl-3-isobutylxanthine↗

PubMed1999

Inducer-specific bidirectional regulation of endothelial interleukin-8 production by thalidomide.

Interleukin-8 (IL-8) is a potent neutrophil chemotaxin, which can also be produced by endothelial cells to facilitate leukocyte emigration. The aim of this study was to determine the effects of the anti-inflammatory drug thalidomide (THD) on chemotaxin release from endothelial cells. Human umbilical vein endothelial cells (HUVEC) were stimulated with tumor necrosis factor alpha (TNFalpha) or endotoxin (LPS) in the presence or absence of various concentrations of THD. Endothelium-derived interleukin-8 (eIL-8) in supernatants was measured using an enzyme-linked immunosorbent assay (ELISA) and biological activity of the harvested eIL-8 was tested in Boyden chamber chemotaxis assays on PMNL. THD itself had no effect on eIL-8 release. Upon stimulation with TNFalpha or LPS, HUVEC produced increased amounts of eIL-8 and THD affected this process in a bidirectional manner, with augmentation of TNFalpha- and inhibition of LPS-effects. Functionality of eIL-8 was confirmed in chemotaxis experiments and by inhibition of chemotactic effects of supernatants with anti-human IL-8 monoclonal antibodies. Results explain and emphasize immunomodulatory properties of THD in cytokine- and endotoxin-induced inflammation and regulation of transendothelial migration.

Anti-Inflammatory Agents, Non-Steroidal↗