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Biomedical subjects

G Zissel

Publications and source records attributed to G Zissel.

At least 19 recordsLinked to original sources
PubMed2000

Accessory function and costimulatory molecule expression of alveolar macrophages in patients with pulmonary tuberculosis.

An effective immune response against M. tuberculosis requires a coordinated interaction of alveolar macrophages (AM) and lymphocytes. Secondary signals, such as accessory function (AF) of antigen presenting cells and interaction of costimulatory molecules are also important for T cell activation. In the present study we determined the AF and the expression of CD11a, CD54, CD58, CD80, CD86 and HLA-DR costimulatory molecules by AMs lavaged from patients with pulmonary tuberculosis and controls. We hypothesized that alterations in AF and costimulatory molecule expression may influence the presentation of tuberculosis. Therefore these parameters were also correlated with the radiographic extension of the disease. AMs of patients with tuberculosis exhibited an increased AF and a significantly increased expression of co-stimulatory molecules compared with controls. Furthermore, we observed that the expression of CD54 (ICAM-1) decreased with the course of the disease. We conclude that the infection by M. tuberculosis results in an increased AF of AMs and the activity of AMs remains uninfluenced by the extension of the disease. Clear-cut changes of patterns of costimulatory molecule expression by AMs could not be observed with the progression of tuberculosis.

Antigens, CD↗
PubMed2000

Human alveolar epithelial cells type II are capable of regulating T-cell activity.

Alveolar epithelial cells type II (AEC-II) express MHC class II on their surface, an important prerequisite for antigen presentation. However, accessory signals are required for an efficient T-cell activation. We therefore isolated AEC-II from tumor-free sections of human lungs obtained by lobectomy/pneumectomy and purified the cells by magnetic-activated cell sorting. Furthermore, we tested the expression of CD54, CD58, CD80, and CD86 on AEC-II and evaluated their accessory function (AF) in cell culture using a coculture of interleukin-2 (IL-2), releasing Jurkat cells and AEC-II. An increased AF is documented by an elevated IL-2 release and expressed as accessory index (AI). In 33 experiments the AF of AEC-II proved to be highly variable. AI ranged between 0.3 and 17.1 with a median of 1.4 (0.3-17.1). Forty-four percent (4-77) of the AEC-II expressed HLA-DR, 44% (12-89%) of the cells expressed CD58, and CD54 was expressed by 55% (16-89%). AEC-II also expressed CD80 and CD86 (38% [0-77%] and 40% [4-68%], respectively). Interestingly, AEC-II released high levels of TGF beta (1730 pg/mL [771-5876]) and the accessory index could be increased (approximately 2-fold) by the addition of neutralizing anti-TGF beta antibodies or radiation. Thus, type II alveolar cells express costimulatory molecules and are able to deliver costimulatory signals for T cells, providing evidence that AEC-II are able to act as antigen-presenting and immunoregulatory cells of the lung. Additionally, the accessory function of AEC-II is under the control of endogenously released TGF beta.

Antigen-Presenting Cells↗
PubMed2000

In vitro release of interleukin-15 by broncho-alveolar lavage cells and peripheral blood mononuclear cells from patients with different lung diseases.

IL-15 shares several biological activities with IL-2 and uses the b and g chain of the IL-2 receptor. In addition to its T-cell stimulating capacity, IL-15 exhibits regulatory properties on macrophage proinflammatory cytokine release. IL-15 is released by non-lymphoid cells, e.g. muscle cells, fibroblasts and monocytes/macrophages. In many lung diseases alveolar macrophages (AM) are activated and release pro- inflammatory cytokines. We asked whether IL-15 is released ex vivo by AM and peripheral blood mononuclear cells (PBMC) from patients with inactive sarcoidosis (PSi), active sarcoidosis (PSa), tuberculosis (TB), hypersensitivity pneumonitis (HSP), cryptogenic fibrosing alveolitis (CFA) and pneumonia (PN). Additionally, we examined the kinetics of the IL-15 release of these cells. During 24 hours of culture, AM from controls (CO) released 3.8 +/- 1.9 pg/ml (mean +/- SD) of IL-15, which was significantly lower than in most of the patient groups (PSa: 8.7 +/- 3.9 pg/ml, TB: 8.4 +/- 1.9 pg/ml, CFA: 5.7 +/- 1.5 pg/ml, and PN: 7. 8 +/- 2.6 pg/ml) except PSi (4.0 +/- 2.6 pg/ml) and HSP (9.3 +/- 9.5 pg/ml). PBMC from patients with PSa released significantly more IL-15 than PBMC from CO (10.8 +/- 8.9 pg/ml versus 6.9 +/- 2.2 pg/ml) whereas PBMC IL-15 release of the other groups did not differ from CO (TB: 5.7 +/- 1.4 pg/ml; CFA: 4.6 +/- 1.6 pg/ml; HSP: 4.9 +/- 3.8 pg/ml). Kinetic studies revealed a minor peak after 5 hours and a major peak from 12 hours to 35 hours for AM and PBMC. In summary, AM from all patient groups but the PSi and the HSP group released increased levels of IL-15, although the total amount of this cytokine is very low.

Alveolitis, Extrinsic Allergic↗
PubMed2000

Effect of proinflammatory cytokines on interleukin-8 mRNA expression and protein production by isolated human alveolar epithelial cells type II in primary culture.

Alveolar epithelial cells type II (AEC-II) are ideally situated to regulate the recruitment and activation of different types of cells through the production of chemokines in response to inflammatory stimulation from the alveolar space. We hypothesized that these cells are important producers of interleukin-8 (IL-8) in the lung. This lead us to investigate the capacity of isolated human AEC-II cells to release IL-8 and whether this IL-8 release is regulated by proinflammatory cytokines, i.e. IL-1 beta, TNF-alpha and IFN-gamma. We isolated AEC-II from tumor-free sections of human lungs obtained by pneumectomy and purified the cells by magnetic activated cell sorting. For control experiments the AEC-II-like cell line A549 was used. IL-8 concentration was measured by ELISA in supernatants of unstimulated and LPS-, IL-1 beta-, TNF-alpha- and IFN-gamma- stimulated cells. IL-8 mRNA expression was evaluated by RT-PCR. Spontaneous IL-8 mRNA expression and protein secretion by AEC-II were significantly higher in comparison with A549 cells. TNF-alpha increased both IL-8 mRNA expression and protein production, whereas IL-1 beta slightly increased IL-8 release but did not change mRNA expression in AEC-II. LPS and IFN-gamma did not influence IL-8 expression in AEC-II and A549 cells. These results show considerable differences between A549 cell and AEC-II. The latter are capable of producing IL-8 under the control of proinflammatory cytokines. Our findings demonstrate that the modulation of IL-8 release in AEC-II may have an important impact on the immunoreactivity of these cells during pulmonary inflammation in vivo.

Cells, Cultured↗
PubMed1999

Lymphocyte transformation test for the evaluation of adverse effects of antituberculous drugs.

The usefulness of the lymphocyte transformation test (LTT) for the analysis of adverse reactions to antituberculous drugs was evaluated. - The LTT was performed with isoniazid and rifampicin in 15 tuberculosis and 2 MOTT (Mycobacteria other than tuberculosis)-infection patients who suffered drug reactions, in 23 patients without any adverse reactions, in 7 controls previously exposed to antituberculous drugs, and in 14 controls who had never been exposed. 4/15 of the hepatotoxic reactions only showed a positive LTT with rifampicin, 3/15 only with isoniazid, and in 8/15 the LTT was negative. In an anaphylactoid shock reaction the LTT was extremely exaggerated for both rifampicin and isoniazid. In patients without any side effects only one slightly increased LTT due to isoniazid was observed. Two healthy controls with previous contact to these drugs showed a positive LTT for isoniazid, one of those with both rifampicin and isoniazid. The LTT was negative in all control persons without any former contact to antituberculous medications. In most cases hepatotoxicity seems to be a pure toxic reaction without the participation of cellular immune mechanisms. LTT can be useful for identifying the drug responsible for immunological side effects.

Adult↗
PubMed1999

Polymorphisms at position -308 in the promoter region of the TNF-alpha and in the first intron of the TNF-beta genes and spontaneous and lipopolysaccharide-induced TNF-alpha release in sarcoidosis.

TNF-alpha is a potent pro-inflammatory cytokine. Previous studies have proved that biallelic polymorphisms in the TNF-alpha (-308, TNFA) and TNF-beta genes (intron 1, TNFB) influence TNF-alpha production. In sarcoidosis, a chronic granulomatous disease, as a result of an unknown in vivo activation bronchoalveolar lavage (BAL) cells release high amounts of TNF-alpha, spontaneously and after in vitro stimulation. Thus, sarcoidosis could serve as a model to test the in vivo effect of TNF gene polymorphisms. We determined the TNFA and TNFB polymorphisms of 44 patients with sarcoidosis and found the following allele frequencies: 0.80, 0.20, 0.38 and 0.62 for TNFA1, TNFA2, TNFB1 and TNFB2, respectively. To examine the in vivo effect of the named polymorphisms on the TNF-alpha production, the spontaneous and LPS-induced TNF-alpha release of BAL cells and peripheral blood mononuclear cells were also determined in patients with sarcoidosis. Statistical analysis did not reveal any significant difference between sarcoidosis patients with different genotypes. The results show that TNFA and TNFB polymorphisms do not determine the level of TNF-alpha release of mononuclear cells activated during the course of sarcoid inflammation.

Alleles↗
PubMed1999

Pharmacological modulation of the IFNgamma-induced accessory function of alveolar macrophages and peripheral blood monocytes.

OBJECTIVE AND DESIGN: Although alveolar macrophages (AM) are poor accessory cells, alveolar macrophages of patients with sarcoidosis or tuberculosis show an elevated accessory function indicating that the accessory function (AF) of AM can be upregulated. MATERIALS AND METHODS: We examined whether the AF of AM and peripheral blood monocytes (PBM) can be increased by interferon-gamma (IFNgamma) and whether immunomodulating drugs like cyclosporine A, cyclophosphamide, dexamethasone, and ambroxol are able to modulate the accessory function and the expression of accessory molecules. RESULTS: IFNgamma increased the AF of AM and PBM up to 309 +/- 122% and 152 +/- 25%, respectively (p < 0.02, unstimulated control = 100%, in all cases). In alveolar macrophages this increase is most efficiently prevented by cyclosporine A (31 +/- 13%), followed by cyclophosphamide (64 +/- 20%) and dexamethasone (66 +/- 20%). In monocytes the IFNgamma-induced increase in accessory function is prevented only by cyclosporine A (17 +/- 7%) and dexamethasone (59 +/- 9%). Cyclosporine A was also the most effective drug downregulating the expression of accessory molecules (CD54, CD58, CD80 and CD86). CONCLUSIONS: In summary, the accessory function of alveolar macrophages and monocytes is upregulated by IFNgamma and can be controled by immunomodulating drugs.

Aged↗
PubMed1999

Analysis of the Kveim-Siltzbach test reagent for bacterial DNA.

The sarcoid spleen-derived reagent for the Kveim-Siltzbach test (KST) elicits a sarcoid-specific, granulomatous, cutaneous response used to establish the diagnosis of sarcoidosis. In the context of the ongoing discussion of a bacterial cause of sarcoidosis we asked the question whether bacterial DNA could be found in the KST reagent. For this purpose two different KST reagents, an identical preparation from a normal spleen, and a native sarcoid spleen were analyzed by polymerase chain reaction (PCR) employing universal primers detecting conserved DNA sequences coding for bacterial ribosomal 16S RNA. Neither KST reagents, the control preparation, nor the spleen yielded a positive signal, indicating that the preparations are free of bacterial contamination. Because the KST reagent elicits granuloma, these results do not support the hypothesis of a bacterial cause of sarcoid granuloma.

Conserved Sequence↗
PubMed1999

Age-related decrease in accessory cell function of human alveolar macrophages.

BACKGROUND: Suboptimal function of an aged immune system may significantly contribute to morbidity and mortality in the elderly. In contrast to lymphocytes, only little is known about changes of cells from the monocyte/macrophage lineage. Especially the changes of their accessory function, which are necessary for optimal T cell stimulation are controversially discussed. METHODS: We measured the accessory function of monocytes (PBM) and alveolar macrophages (AM) and correlated their accessory function with the age of the patients. RESULTS: We found a significant decrease in accessory function of AM with the age (rs = -0.5, P < 0.006) but not of PBM (rs = -0.4, P > 0.1). Additionally, we found a significant decrease in the percentage of AM (rs = 0.3, P < 0.005) and an increase in the percentage of lymphocytes (rs = 0.3, P < 0.02) in the bronchoalveolar lavage. No correlations could be found with other lavage parameters or with unstimulated in vitro TNF-alpha, TGF-beta, and IL-6 release of bronchoalveolar lavage cells; however, in stimulated BAL-cell cultures we found a weak but significant correlation between TNF-alpha release and the age (rs = -0.3, P < 0.02). CONCLUSIONS: Impairment of accessory cell function of alveolar macrophages may contribute to an increased risk of pulmonary infection of elderly persons.

Adult↗
PubMed1999

Different cytokine patterns correlate with the extension of disease in pulmonary tuberculosis.

The relative amounts of different pro- and anti-inflammatory cytokines released at the site of infection by bronchoalveolar lavage (BAL) cells may influence the presentation of tuberculosis. To investigate this hypothesis the in situ release by BAL cells of the following cytokines was measured and correlated with the chest X-ray findings of 43 patients with pulmonary tuberculosis: interleukin (IL)-8, macrophage inflammatory protein-1alpha (MIP-1alpha), IL-6, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), interferon-gamma (IFN-gamma), IL-2, IL-4 and IL-5. The release of IL-8 and IL-6 decreased with the progression of the disease, while the release of MIP-1alpha was increased in patients with advanced tuberculosis. The release of TNF-alpha and TGF-beta did not differ between patients with or without cavitary lesions. The Th1 (IFN-gamma and IL-2) and Th2 (IL-4 and IL-5) cytokine release exhibited a gradual increment with the advance of tuberculosis. Thus, our data provide evidence that a Th0 cytokine pattern is predominant at the site of pulmonary tuberculosis. In conclusion, immunoparalysis status could not be observed in our patients with severe tuberculosis.

Bronchoalveolar Lavage Fluid↗
PubMed1999

[Diagnosis of chronic berylliosis].

The diagnostic value of the lymphocyte transformation test (BeLT) and the intracutaneous skin test with berylliumsulfate was addressed in 13 patients with chronic berylliosis, and 15 individuals with occupational exposure. Additionally, patients with sarcoidosis (n = 21), tuberculosis (n = 14) and healthy controls (n = 25) were tested with BeLT and yielded negative results. In chronic berylliosis the BeLT was positive in 10/13. In 3/13 the BeLT was negative, but the skin test positive. 6/15 exposed individuals exhibited a positive BeLT. The time course of the skin test differed markedly between the individual berylliosis patients. Typical granulomas were present in 4/10 cases. In 9 exposed individuals BeLT tested negative. Additionally, skin tests were negative in 7 exposed patients, however, unspecific skin reactions were observed in 3 cases. The diagnostic value of Beryllium IT requires further investigation. At present, BeLT appears to be a suitable test to prove beryllium sensitisation.

Adult↗
PubMed1998

Soluble intercellular adhesion molecule 1 (sICAM-1) in bronchoalveolar lavage (BAL) cell cultures and in the circulation of patients with tuberculosis, hypersensitivity pneumonitis and sarcoidosis.

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in inflammatory diseases. It is believed that its soluble form (sICAM-1) might be a serum parameter of inflammatory activity with possible relevance in granulomatous disorders. To evaluate this role we measured sICAM-1 by ELISA in serum and shedding of this molecule by BAL cells in patients with granulomatous lung diseases (pulmonary tuberculosis (TB), hypersensitivity pneumonitis (HSP), pulmonary sarcoidosis (PS), and controls). Serum concentrations of sICAM-1 in patients with TB (496.9 +/- 49.7 ng/ml), with HSP (636.5 +/- 85.9.8 ng/ml), and with PS (588.3 +/- 72.2 ng/ml) were significantly increased compared to controls (275.7 +/- 33.1 ng/ml). Spontaneous release of sICAM-1 by BAL cells differed among patient groups (TB: 9.3 +/- 1.7; HSP: 17.5 +/- 1.4; PS: 9.7 +/- 1.5 ng/ml), however, exceeding that of controls significantly (3.8 +/- 0.6 ng/ml). No correlations between the circulating level and the shedding of this molecule by BAL cells were observed within the groups. Significant correlations between serum sICAM-1 and serum tumor necrosis factor alpha (TNFalpha) level were observed in patients with HSP and TB. Kinetic cell culture experiments with BAL cells revealed a dissociation in sICAM-1 shedding and TNFalpha release. After stimulation rapid upregulation of both molecules (5 h) was followed by a cessation of TNFalpha production at 28 h. sICAM-1 shedding, however, was maintained over 2 days. Our results evidence that the circulating pool of sICAM-1, as well as the shedding of this molecule by BAL cells reflect the activity of cells in the inflammatory processes of granulomatous diseases.

Adult↗
PubMed1998

Serum level of interleukin 8 is elevated in idiopathic pulmonary fibrosis and indicates disease activity.

It has been shown that interleukin 8 (IL-8) is increased in bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF) and there is increasing evidence that it is involved in the pathogenesis of this disease. To date, no data are available as to whether IL-8 is elevated in sera of IPF patients. We obtained sera from 42 patients with IPF and 20 healthy controls at time of BAL. From 20 of 42 patients with IPF and 12 of 20 controls BALF was available, enabling us to measure IL-8 in serum and BALF of the same time point. IL-8 was significantly elevated in serum (54.7 +/- 7.5 pg/ml, p < 0.0001) and BALF (715.7 +/- 112.4 pg/ml, p < 0.0001) of patients with IPF compared with controls (IL-8 in serum, 5.2 +/- 0.8 pg/ml; IL-8 in BALF, 67.3 +/- 9.7 pg/ml). We observed a significant positive correlation between IL-8 levels in BALF and percentage of BALF neutrophils (p < 0.001) and between serum IL-8 and BALF IL-8 levels (p < 0.005) in patients with IPF. Consequently, the serum IL-8 level correlated positively with the percentage of BAL neutrophils (p < 0.01), indicating that it may reflect the degree of neutrophilic alveolitis in IPF. Furthermore, the serum IL-8 level showed a negative correlation with important indicators of impairment of lung function (DL(CO), TLC, VC) and PaO2. In conclusion, we were able to demonstrate that the degree of neutrophilic alveolitis in IPF is reflected by increased serum levels of IL-8 and we suggest that the serological assessment of IL-8 may provide a useful parameter for clinicians in monitoring patients with IPF.

Anti-Inflammatory Agents↗
PubMed1998

Increased expression of proinflammatory chemokines in bronchoalveolar lavage cells of patients with progressing idiopathic pulmonary fibrosis and sarcoidosis.

BACKGROUND: There is increasing evidence that the proinflammatory chemokines interleukin-8 (IL-8) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) are involved in the pathogenesis of interstitial lung diseases. METHODS: We investigated the release of TNF-alpha, IL-8, MIP-1 alpha by cultured bronchoalveolar lavage (BAL) immune cells of patients with idiopathic pulmonary fibrosis (IPF, n = 24), sarcoidosis (SAR, n = 24), and controls (n = 20) by ELISA. Furthermore, mRNA expression of these cytokines in BAL cells immediately frozen after bronchoscopy was determined. The clinical course of the disease was evaluated and the patients were subdivided into groups with progressing or stable disease. RESULTS: TNF-alpha, IL-8, and MIP-1 alpha were significantly elevated in the supernatants of BAL immune cells of IPF and SAR patients with progressing disease compared to controls (p < 0.005 in both diseases) and also when compared to patients with stable disease (IPF p < 0.005, SAR p < 0.05). Interestingly, the release of TNF-alpha, IL-8, and MIP-1 alpha did not differ significantly between IPF patients with stable disease and controls, whereas in SAR patients with stable disease a difference at a low significance level (p < 0.05) was obtained. In IPF and SAR patients with progressing disease, a clear mRNA signal of TNF-alpha, IL-8, and MIP-1 alpha was detected in BAL immune cells not having been stimulated by adherence to plastic, whereas in patients with stable disease or controls only a weak signal was observed. MIP-1 alpha release correlated positively with percentage of BAL eosinophils in IPF and SAR. Furthermore, the percentage of eosinophils in BAL was significantly elevated in the IPF subgroup with progressing disease. CONCLUSIONS: Our data demonstrate that an exaggerated expression of TNF-alpha, IL-8, and MIP-1 alpha in BAL immune cells is characteristic for IPF and SAR patients who show progressing disease.

Adult↗
PubMed1997

Reduction of cytokine release of blood and bronchoalveolar mononuclear cells by ambroxol.

Ambroxol is a mucolytic agent frequently used in the treatment of chronic bronchitis. It has been reported, following clinical and in-vitro studies, that ambroxol exhibits an anti-inflammatory action. This capability was investigated by activating bronchoalveolar lavage cells and peripheral blood mononuclear cells in-vitro to elicit the release of tumor necrosis factor alpha, interleukin-2 and interferon gamma, whilst simultaneously exposing them to varying pharmacological concentrations of ambroxol (10, 1, and 0.1 microM). After 24 h it was observed that the isolated tissue-culture supernatants showed a dose-dependent reduction in the concentration of the tested cytokines; 10 microM (12 to 37% reduction) and 1 microM to (6 to 27% reduction). At 0.1 microM, a significant reduction could only be observed in the release of interleukin-2 by bronchoalveolar lavage cells. These results demonstrate, that ambroxol exhibits anti-inflammatory actions in concentrations achievable in vivo.

Ambroxol↗
PubMed1997

Shed soluble ICAM-1 molecules in bronchoalveolar lavage cell supernatants and serum of patients with pulmonary sarcoidosis.

The soluble form of intercellular adhesion molecule-1 (sICAM-1) might be a serum parameter of inflammatory activity gauging cellular interactions with possible relevance in sarcoidosis. To address this question we measured sICAM-1 by enzyme-linked immunosorbent assay in serum and shedding of this molecule by bronchoalveolar lavage (BAL) cells in sarcoidosis patients (44 and 40, respectively) and in controls (10 and 19, respectively). Serum concentrations of sICAM-1 (588.3 +/- 72.2 ng/ml) and its spontaneous release by BAL cells (9.9 +/- 1.5 ng/ml) in patients with active sarcoidosis were significantly higher than in those with inactive disease or controls, although no correlation was observed. Significant correlations of sICAM-1 shedding by nonstimulated BAL cells with the serum level of neopterin and of shedding by lipopolysaccharide-stimulated BAL cells with percentage of alveolar macrophages were observed in active sarcoidosis. Kinetic cell culture experiments with peripheral blood mononuclears disclosed a rapid up-regulation of sICAM-1 shedding and tumor necrosis factor-alpha release; however, at 5 h after stimulation a dissociation of their releases was observed. sICAM-1 release was maintained over 2 days, whereas tumor necrosis factor-alpha release peaked at 5 and ceased after 43 h. These results provide evidence that circulating and BAL cell culture-derived sICAM-1 reflect the stage of sarcoid inflammation. Although sICAM-1 in BAL cell supernatants originates from alveolar macrophages; the absence of a correlation with serum sICAM-1 concentration indicates that other cells are additional sources of the circulating pool of this molecule.

Adult↗