Search PubMed⌕ Search

Biomedical subjects

H Matthys

Publications and source records attributed to H Matthys.

At least 37 records · Page 2Linked to original sources
PubMed2000

Th1 cytokine pattern in sarcoidosis is expressed by bronchoalveolar CD4+ and CD8+ T cells.

The pathogenesis of pulmonary sarcoidosis has been related to an increased production of Th1-like cytokines. However, cytokine expression in sarcoidosis has not been systematically studied at a single-cell level. We therefore investigated the expression of IL-2, IL-4, IL-13, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) intracellularly in bronchoalveolar lavage (BAL) and peripheral blood CD3+ T lymphocytes from patients with pulmonary sarcoidosis (radiologic stage II-III, n = 8) and normal controls (n = 9) by flow cytometry. In contrast to IL-4 and IL-13, the percentage of T lymphocytes expressing intracellular IL-2 (49.3 +/- 21.3% versus 14.5 +/- 15.6%), IFN-gamma (75.5 +/- 14.9% versus 32.6 +/- 18.7%) and TNF-alpha (68.3 +/- 18.7% versus 36.8 +/- 20.8%) was significantly higher in patients with sarcoidosis than in normal controls (each P < 0.005). In contrast to BAL lymphocytes, expression of these cytokines in peripheral blood lymphocytes did not differ between patients with sarcoidosis and normal controls. Close correlations were observed between the percentages of BAL lymphocytes expressing intracellular IL-2, IFN-gamma and TNF-alpha, but not for IL-4 or IL-13. Analysis of the expression of these cytokines in T lymphocyte subsets revealed IL-2, IFN-gamma, and TNF-alpha in CD4+ as well as CD8+ T lymphocytes, suggesting a contribution of TC1 cells to the production of proinflammatory cytokines in sarcoidosis. We conclude that a Th1-like cytokine pattern can be observed in CD4+ as well as in CD8+ BAL T lymphocytes in patients with pulmonary sarcoidosis.

Adult↗
PubMed2000

Effects of interferon-gamma and tumour necrosis factor-alpha on CD95/Fas ligand-mediated apoptosis in human blood eosinophils.

Many cells, including eosinophils, express CD95 (Fas), a surface receptor that mediates apoptosis when ligated by specific antibodies or its natural ligand, Fas ligand (FasL). As apoptosis may play an important role in the regulation of tissue eosinophilia, factors that modulate eosinophil sensitivity to apoptosis are of great interest. It has previously been shown that interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) together increase CD95 surface expression on eosinophils. However, the functional consequences of this increase in CD95 expression have not been demonstrated in detail. We therefore investigated whether the increase in CD95 expression mediated by IFN-gamma/TNF-alpha indeed translates into increased, FasL-mediated apoptosis of eosinophils. For this purpose, purified eosinophils from normal donors were incubated with different concentrations of FasL and induction of apoptosis was assessed by annexin-V/propidium iodide assay. Unlike Jurkat cells, which became apoptotic within 2 h after incubation with FasL, an increase in eosinophil apoptosis could first be dedicated after 6 h incubation with FasL. Prestimulation with IFN-gamma/TNF-alpha for 24 h significantly enhanced FasL-induced apoptosis in eosinophils. This increase in CD95/FasL-mediated apoptosis was correlated with an IFN-gamma/TNF-alpha-mediated increase in CD95 expression. From these findings we conclude that the combination of IFN-gamma and TNF-alpha enhances CD95 expression, which results in an increase in FasL-mediated apoptosis of eosinophils in vitro.

Apoptosis↗
PubMed2000

Efficacy and tolerability of myrtol standardized in acute bronchitis. A multi-centre, randomised, double-blind, placebo-controlled parallel group clinical trial vs. cefuroxime and ambroxol.

UNLABELLED: Myrtol standardized (Gelomyrtol forte) is a phytotherapeutic extract (distillate) consisting mainly of three monoterpenes: (+)alpha-pinene, d-limonene and 1,8-cineole. OBJECTIVE: This study describes and compares the efficacy, safety and tolerability of a 2-week treatment with myrtol stand. (4 x 300 mg, day 1-14), cefuroxime (CAS 55268-75-2) (2 x 250 mg daily for day 1-6), ambroxol (CAS 18683-91-5) (3 x 30 mg for day 1-3, 2 x 30 mg for days 4-14) and matched placebo in acute bronchitis. PATIENTS: 676 male and female outpatients, aged > or = 18 years, with acute bronchitis of recent onset (within last 5 days), with an FEV1 > 75% of the normal EGKS-value and without evidence or suspicion of chronic pulmonary disease or any further confounding illness were included in the study. INTERVENTION: Patients were randomly assigned to a 2-week treatment course with either myrtol stand. (N = 170), cefuroxime (N = 171), ambroxol (N = 163) or placebo (N = 172) in a double-blind, placebo-matched, parallel-group fashion. Evaluations were at baseline (visit 1), after 1 and 2 weeks of treatment (visits 2 and 3) and at 2 weeks after conclusion of the treatments (visit 4). CRITERIA: Responder- and non-responder rates (primary), signs (abnormal auscultation), symptoms (daily diary data on nightly cough, coughing fits during the day, sputum consistence and general well-being; visit data on bronchial hyperreactivity and absence/presence of associated symptoms), FEV1, overall efficacy, absence of relapse, safety and tolerability (adverse events, laboratory screens, vital signs and physical examination). Criteria were evaluated for the intention-to-treat data-set (ITT) and the 'efficacy evaluable' sample (EAP), i.e. excluding patients with missing values (incl. discontinued non-responders and drop-outs for other reasons) at the time of assessment. RESULTS: The signs and symptoms of acute bronchitis regressed readily in all treatment groups, but regression was slower and less complete in the patients treated with placebo. In patients treated with placebo, the acute bronchitis was considered to have deteriorated to such an extent that discontinuation was indicated ('non-responder') in 36 patients (ITT: 20.9%, 95% CI: 15.1 to 27.8% and EAP: 21.3%, CI: 15.4 to 28.3%) after 1 week (visit 2) and in 19 further patients (ITT: 11.0%, CI: 6.8 to 16.7%; EAP: 14.8%, CI: 9.2 to 22.2%) after 1 further week (visit 3). In contrast, in the group of patients treated with myrtol stand. the non-responder rates at visits 2 and 3 were only 5.3% (ITT, CI: 2.4 to 9.8%; EAP: 5.4%, CI: 2.5 to 10.0%) and 1.2% (ITT, CI: 0.1 to 4.2%; EAP: 1.3%, CI: 0.2 to 4.7%); the responder rates at visit 2 were statistically significantly higher (p < 0.001) for myrtol stand. (ITT: 92.9%, CI: 88.0 to 96.3) compared to placebo (ITT: 77.3%, CI: 70.3 to 83.4), and similar to those for cefuroxime (ITT: 92.4%, CI: 87.4 to 95.9) and ambroxol (ITT: 89.6%, CI: 83.8 to 93.8%). The superiority of the active treatments vs. placebo with little difference among the treatments was confirmed for all further criteria of evaluation. There was no evidence of bronchoconstriction or relapse in any treatment group for the patients continuing treatment (i.e. for those who were not discontinued because of non-response). The treatments were safe and comparably well tolerated. CONCLUSION: Compared to placebo, treatment with myrtol stand. was well tolerated but evidently superior in terms of efficacy, resulting in a more rapid and more complete recovery; although well comparable with the other active treatments, myrtol stand. tended to be superior to cefuroxime and ambroxol for several ancillary criteria. Myrtol stand. is a well-evidenced alternative to antibiotics for acute bronchitis without specified infective agent, without the risk to promote the development of bacterial resistance.

Acute Disease↗
PubMed2000

[Increase in perforin-positive peripheral blood lymphocytes in extrinsic and intrinsic asthma].

The cause of asthma which has been linked to a chronic, T-cell-mediated bronchial inflammation, remains unclear. A number of other T-lymphocyte-mediated, chronic inflammatory disorders have been associated with autoimmunity and there are data indicating that autoimmune phenomena might also be present in asthma. Expression of perforin, a cytotoxic molecule produced by lymphocytes, has been implicated in the pathogenesis of autoimmune disease. We therefore tested the hypothesis that allergic and intrinsic asthma might be associated with an increase in lymphocytes producing perforin by comparing the expression of intracellular perforin in peripheral blood lymphocytes of patients with extrinsic asthma (n = 13), intrinsic asthma (n = 7), and healthy (control subjects (n = 18). Lymphocytes were identified using flow cytometry and subdivided into CD3(+), CD4(+), CD8(+), CD16(+), and CD56(+) subpopulations after staining with appropriate monoclonal antibodies. The percentage of perforin-positive total lymphocytes as significantly elevated in patients with allergic as well as intrinsic asthma when compared with normal control subjects. Analysis of lymphocyte subpopulations also revealed a significant increase in the percentage of CD3(+), CD4(+), CD8(+), and CD56(+) cells expressing perforin in allergic asthma and a significant increase in the percentage of CD4(+), and CD56(+) cells in intrinsic asthma when compare with healthy control subjects. Perforin expression in CD4(+) cells in intrinsic asthma was also significantly elevated compared with allergic asthma. We conclude that allergic and intrinsic asthma is associated with increased expression of perforin in T-lymphocyte subsets.

Adult↗
PubMed2000

Increase in perforin-positive peripheral blood lymphocytes in extrinsic and intrinsic asthma.

The cause of asthma, which has been linked to a chronic, T-cell-mediated bronchial inflammation, remains unclear. A number of other T-lymphocyte-mediated, chronic inflammatory disorders have been associated with autoimmunity and there are data indicating that autoimmune phenomena might also be present in asthma. Expression of perforin, a cytotoxic molecule produced by lymphocytes, has been implicated in the pathogenesis of autoimmune diseases. We therefore tested the hypothesis that allergic and intrinsic asthma might be associated with an increase in lymphocytes producing perforin by comparing the expression of intracellular perforin in peripheral blood lymphocytes of patients with extrinsic asthma (n = 13), intrinsic asthma (n = 7), and healthy control subjects (n = 18). Lymphocytes were identified using flow cytometry and subdivided into CD3(+), CD4(+), CD8(+), CD16(+), and CD56(+) subpopulations after staining with appropriate monoclonal antibodies. The percentage of perforin-positive total lymphocytes was significantly elevated in patients with allergic as well as intrinsic asthma when compared with normal control subjects. Analysis of lymphocyte subpopulations also revealed a significant increase in the percentage of CD3(+), CD4(+), CD8(+), and CD56(+) cells expressing perforin in allergic asthma and a significant increase in the percentage of CD4(+) and CD56(+) cells in intrinsic asthma when compared with healthy control subjects. Perforin expression in CD4(+) cells in intrinsic asthma was also significantly elevated compared with allergic asthma. We conclude that allergic and intrinsic asthma is associated with increased expression of perforin in T-lymphocyte subsets.

Adult↗
PubMed1999

Differential modulation of interleukin-4 and interleukin-13 secretion from human peripheral blood mononuclear cells.

Interleukin-4 (IL-4) and IL-13 which have been implicated in the pathogenesis of atopic reactions elicit many of the same biologic responses. Therefore, time- and stimulus-dependent differences in the regulation of IL-4 and IL-13 production could be of relevance to their biological effects. In this study we tested the hypothesis that stimulation of peripheral blood mononuclear cells (PBMCs) with different inducers of cell activation would result in a differential expression of IL-4 and IL-13. For this purpose, PBMCs of nonatopic volunteers were incubated with phytohaemagglutinin (PHA), phorbolester (PMA), calcium ionophore A23187, or IL-3. The effect of these stimuli on IL-4 and IL-13 production were analysed by enzyme-linked immunoassay (ELISA) in supernatants of cultured PBMCs. Incubation of PBMCs with A23167 and PHA induced both a dose- and time-dependent increase in IL-4 and IL-13 release. A23187 induced concentrations of IL-4 were higher than those of IL-13 whereas IL-4 release following stimulation with PHA was considerably higher for IL-13 compared to IL-4. In contrast, there was a selective increase in IL-13 but not IL-4 concentrations following stimulation of PBMCs with PMA and IL-3 in vitro. In conclusion in this study evidence is provided that IL-4 and IL-13 production are regulated differently which might explain their functional redundancy.

Calcimycin↗
PubMed1999

Modulation of cytokine release from mononuclear cells by prostacyclin, IL-4 and IL-13.

In a previous study, we reported that cicaprost, a stable prostacyclin analogue can inhibit the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) from activated human peripheral mononuclear blood cells (PBMCs). Since interleukin (IL-4) and IL-13 have been shown to inhibit the release of cytokines from PBMCs we tested the hypothesis that prostacyclin in combination with IL-4 or IL-13 can act synergistically to modulate the release of IL-10, generally associated with anti-inflammatory properties, and the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha). For this purpose, PBMCs were isolated over Ficoll, stimulated with lipopolysaccharide (LPS) and incubated in the presence of cicaprost, IL-4 or IL-13. There was a significant reduction in TNF-alpha as well as IL-10 secretion from LPS-stimulated PBMCs following incubation with IL-4 or IL-13. In contrast, cicaprost reduced the secretion of TNF-alpha but led to a slight enhancement of IL-10 release from PBMCs. When LPS-activated PBMCs were incubated in the presence of cicaprost and IL-4 or IL-13 there was a selective, synergistic inhibition of the TNF-alpha release which was not observed for IL-10. Thus, our data suggest that prostacyclin can synergize with cytokines to selectively inhibit the release of pro-inflammatory cytokines from PBMCs.

Cell Survival↗
PubMed1999

Synergistic effects of interleukin-4 or interleukin-13 and tumor necrosis factor-alpha on eosinophil activation in vitro.

Increased concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-4, and IL-13 have been measured in bronchoalveolar lavage fluid (BALF) of patients with asthma following allergen provocation. In addition, these cytokines have also been reported to activate eosinophils in vitro. Although cytokine interactions have been postulated in the activation of eosinophils, the combined effects of cytokines on eosinophil activation remain poorly understood. Because activation of eosinophils has been regarded as a crucial event in the pathogenesis of asthmatic inflammation, we tested the hypothesis that IL-4 and IL-13 could enhance the effects of TNF-alpha on eosinophil activation. For this purpose, eosinophils from normal donors were purified and cultured in the presence of IL-4 or IL-13 and TNF-alpha. Eosinophil survival and surface expression of CD69 were assessed by flow cytometry. There was a concentration- and time-dependent upregulation in CD69 expression as well as eosinophil survival when eosinophils were incubated with IL-13, IL-4, or TNF-alpha. However, eosinophil viability and CD69 expression increased synergistically when eosinophils were incubated with IL-13 or IL-4 in the presence of TNF-alpha. This synergistic effect of IL-4 and IL-13 on CD69 expression was not limited to TNF-alpha but was also observed with IL-5. Our study provides evidence that IL-4 can activate eosinophils in a similar fashion as does IL-13. Furthermore, this study shows that the addition of IL-4 or IL-13 to TNF-alpha or IL-5 has synergistic effects on eosinophil activation, suggesting that the combined effects of different cytokines present in BALF following allergen provocation can enhance eosinophil activation in vitro.

Antigens, CD↗
PubMed1999

CD69 surface expression on human lung eosinophils after segmental allergen provocation.

CD69 expression on eosinophils is observed in asthma and has been proposed as a marker of eosinophil activation. The role of allergens in the in vivo regulation of CD69 expression on eosinophils, however, remains incompletely understood. It was therefore investigated whether CD69 expression on eosinophils can be induced by allergen provocation in vivo. Ten allergic asthmatics were studied by segmental allergen provocation. Two segments of the right and left lung were challenged with allergen or saline. CD69 expression was determined by flow cytometry and concentrations of interleukins were analysed by enzyme-linked immunosorbent assay in bronchoalveolar lavage (BAL) fluid. Expression of CD69 on BAL eosinophils in the segments lavaged 10 min following saline instillation (28.3+/-8.8 specific mean fluorescence (SMF)) was not significantly different to segments lavaged 10 min after allergen (80.2+/-21.8 SMF) and segments lavaged 18 h after saline challenge (87.2+/-23.3 SMF). However, CD69 expression on eosinophils increased significantly 18 h after allergen challenge (128.6+/-21.9 SMF, p<0.03) which was accompanied by elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations (114.9+/-42.9 pg x mL(-1), p<0.05). CD69 expression on eosinophils and GM-CSF concentrations correlated 18 h following allergen provocation (r = 0.7, p<0.025). These results suggest that in allergic asthma there is an allergen dependent, endobronchial upregulation of eosinophil activation as assessed by CD69 expression on eosinophils.

Adult↗
PubMed1998

Differential regulation of CD95 (Fas/APO-1) expression in human blood eosinophils.

CD95 (Fas, APO-1) is a cell surface receptor expressed on many cells including eosinophils which mediates apoptosis when ligated by agonistic antibodies or its natural ligand FasL. Since inhibition of apoptosis may play an important role in controlling tissue eosinophilia, we investigated the expression of CD95 on purified peripheral blood eosinophils from normal donors. Freshly isolated eosinophils expressed CD95 on the cell surface as well as CD95-specific mRNA at low levels which did not change during 24-h culture. Incubation of eosinophils with IL-3, IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) did not modulate the basal expression of CD95. IFN-gamma as well as TNF-alpha, however, induced a significant, dose- and time-dependent increase in CD95 mRNA and cell surface expression as measured by reverse transcription-PCR and flow cytometry. Co-stimulation with IFN-gamma and TNF-alpha had synergistic effects on the CD95 surface expression on eosinophils. Addition of IL-3, IL-5 or GM-CSF to IFN-gamma- and TNF-alpha-stimulated eosinophils caused in a reduction of CD95 expression. Functional activity for CD95 following incubation with IFN-gamma and TNF-alpha was demonstrated by increased apoptosis in response to cross-linking with FasL. From these data, we conclude that IFN-gamma and TNF-alpha can up-regulate cell surface expression of CD95 on eosinophils, which leads to an increased susceptibility of eosinophils to Fas-mediated apoptosis. Thus, our results suggest that receptors involved in eosinophil apoptosis can be regulated by antagonistic cytokines.

Apoptosis↗
PubMed1998

Efficacy of chlorofluorocarbon-free beclomethasone dipropionate 400 micrograms day-1 delivered as an extrafine aerosol in adults with moderate asthma.

Beclomethasone dipropionate (BDP) has been reformulated in a chlorofluorocarbon-free propellant, hydrofluoroalkane-134a (HFA), resulting in an extrafine aerosol which gives improved drug delivery to the airways. The objective of this 6 week, placebo-controlled study was to evaluate the clinical efficacy of HFA-BDP 400 micrograms day-1 in 256 adult patients with moderate asthma. This is a lower daily dose than that recommended for existing BDP inhalers in current treatment guidelines for moderate asthma (NIH publication 95-3659). Another objective was to evaluate whether delivering the 400 micrograms dose as four actuations of 50 micrograms twice daily (HFA-BDP 50 micrograms) provided equivalent asthma control to delivering the dose as two actuations of 100 micrograms twice daily (HFA-BDP 100 micrograms) without the use of a spacer or holding chamber. Both active treatments produced a significant change from baseline in morning peak expiratory flow (PEF), which was significantly larger than that in the placebo group (P < or = 0.017) throughout the study. The mean changes from baseline in morning PEF at weeks 5-6 were 47.0 l min-1 in the combined HFA-BDP group and 16.5 l min-1 in the HFA-placebo group. The two dose strengths were statistically equivalent (P = 0.017 for equivalence testing). The active treatments also produced significant improvements compared with placebo in evening PEF, forced expiratory volume in the first second, forced expiratory flow over 25-75% of vital capacity, sleep disturbance scores and daily beta-agonist use. The study medication was well tolerated, with a low incidence of adverse events. The results from this study demonstrate that a daily dose of 400 micrograms HFA-BDP (given in 50 micrograms and 100 micrograms strengths) provides dose proportionality and effective control in patients with moderate asthma.

Administration, Inhalation↗