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G Zissel

Publications and source records attributed to G Zissel.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1997

TCR V beta families in T cell clones from sarcoid lung parenchyma, BAL, and blood.

The TCR repertoire and the CD4/CD8 ratio of clones from peripheral blood (PB), transbronchial biopsies (TBB), and bronchoalveolar lavage (BAL) of 16 sarcoid patients was analyzed by staining the clones with monoclonal antibodies against nine V beta-families. We observed a striking increase in the CD4/CD8 ratio of the clones from BAL; whereas the CD4/CD8 ratio of the clones from PB was in the normal range. The CD4/CD8 ratio of the TBB-clones had also increased, but this increase did not reach the level of that of the BAL clones. The most prominent changes in the V beta percentages could be detected in the CD4+ subpopulation of the BAL-clones. The most abundant V beta families were V beta 5 in PB and BAL (11.8 and 28.6%, respectively) and V beta 6 in the TBB (12.4%). A similar compartmentalized V beta usage could be demonstrated in one patient with tuberculosis and one patient with HP. The increase in V beta 5, V beta 8, V beta 12, V beta 13.3, and V beta 19 in the BAL and the increase of V beta 5, V beta 6, V beta 13.3, and V beta 19 in the TBB suggest an antigen-driven activation of the T cells in both compartments. Differences in the V beta percentages between BAL and TBB and the lower CD4/CD8 ratio in the TBB, however, demonstrate a relative independence of the two compartments.

Biopsy↗
PubMed1997

Sarcoidosis: TNF-alpha release from alveolar macrophages and serum level of sIL-2R are prognostic markers.

At the time of diagnosis, many sarcoidosis patients have no clinical indication for corticosteroid therapy, and prognostic parameters predicting deterioration are missing. In the present study, we investigated parameters derived from bronchoalveolar lavage (BAL) and serum in 77 patients with recently diagnosed sarcoidosis to test their predictive value. Patients were divided into a group with (Group A, n = 37) and a group without (Group B, n = 40) indications for therapy, and the course of the disease was evaluated after 5.7 +/- 0.4 mo. The CD4+/CD8+ lymphocyte ratio and percentage of BAL lymphocytes were of no predictive value. Release of tumor necrosis factor-alpha (TNF-alpha) from cultured alveolar macrophages (AM) was significantly increased in both groups (Group A = 1,872 +/- 428 pg/ml; Group B = 1,561 +/- 449 pg/ml) as compared with controls (220 +/- 37 pg/ml). In Group B, however, patients with a high level of TNF-alpha release had a significantly greater risk of disease progression than did those with normal TNF-alpha release (43.8% versus 8.3%, respectively). From the serologic parameters investigated, consisting of neopterin, angiotensin converting enzyme (ACE), and soluble interleukin-2 receptor (sIL-2R), only the last was of significant predictive value; 42.1% of sarcoidosis patients in Group B with a high level of sIL-2R experienced disease progression, whereas none of those with a normal level did. We conclude that TNF-alpha release and sIL-2R are suitable parameters for predicting disease progression in sarcoid patients who have no indication for therapy at the time of disease diagnosis.

Adult↗
PubMed1997

Th1/Th2 cell distribution in pulmonary sarcoidosis.

Cytokines released by T lymphocytes activated in the course of sarcoidosis, e.g., interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), indicate the presence of Th1 cells leading to the question of Th1/Th0/Th2 balance in sarcoidosis. The aim of this study was to evaluate Th-like cytokine patterns in different compartments of the body, i.e., peripheral blood, pulmonary parenchyma, and bronchoalveolar lavage (BAL), of patients with pulmonary sarcoidosis by comparing cytokine gene expression of 167 T-cell clones derived from the above-mentioned compartments. Seventy-nine blood, 49 transbronchial biopsy, and 39 BAL clones were analyzed using polymerase chain reaction to identify the respective gene transcripts. The majority of CD4+ and CD8+ blood cells exhibited intermediate cytokine profiles (63.3%) without shifts to either side of the spectrum (6.3% Th1, 5.1% Th2). Lung parenchyma cells shifted to the Th1 side of the spectrum: 26.5% of the cells were of Th1 or of intermediate type (between Th1 and Th0), whereas only 8.1% of the cells were of Th2 or of intermediate type (between Th0 and Th2). CD8+ parenchyma cells were evenly distributed. From BAL only CD4+ clones could be generated with shifts to both ends of the spectrum. Thus, our data provide evidence that in sarcoidosis, at the site of granuloma formation, an accumulation of Th1 cells as well as of intermediate (between Th1 and Th0) cell types occurs, whereas in the alveolar lumen, high numbers of Th1 and Th2 cells with a simultaneous decrease of Th0 cells can be observed.

CD4-Positive T-Lymphocytes↗
PubMed1997

Anti-Borrelia burgdorferi immunoglobulin seroprevalence in pulmonary sarcoidosis: a negative report.

The aetiology of sarcoidosis is still unknown. An infectious microorganism as causal agent for this disease could not be identified, but high titres of antibodies against Borrelia burgdorferi were detected in Chinese studies implying a causality with this disease. These findings, however, could not be reproduced by other researchers. The aim of this study was, therefore, to evaluate the possible role of these spirochetes in the pathogenesis of sarcoidosis by serological examinations. Sixty sera of patients suffering from sarcoidosis were examined for anti-B. burgdorferi immunoglobulin by enzyme-linked immunosorbent assay (ELISA). ELISAs for these antibodies show a high sensitivity, but a low specificity; therefore, a specific immunoblot was used to confirm positive results. Initially, 8% of the patients were reactive in the ELISA, and 20% of these could be confirmed by immunoblot. Therefore, the prevalence for B. burgdorferi antibodies in sarcoidosis patients was 1.6%. This result did not differ significantly from the prevalence of B. burgdorferi antibodies in 1,000 regular blood donors of the city of Hamburg (7% reactive in the ELISA, 38% confirmed via immunoblot, prevalence 2.7%). The hypothesis of causality between a B. burgdorferi infection and sarcoidosis cannot be confirmed by this data.

Antibodies, Bacterial↗
PubMed1997

Accessory function of alveolar macrophages from patients with sarcoidosis and other granulomatous and nongranulomatous lung diseases.

BACKGROUND: Accessory function (AF) is one way antigen presenting cells generate sufficient secondary signals for optimal T-cell proliferation and IL-2 production. In general, alveolar macrophages (AM) are inferior accessory cells in comparison to monocytes whereas in sarcoidosis AF of AM is increased. METHODS: We compared the accessory index (AI) of AM and peripheral blood monocytes (PBM) of 41 patients with inactive sarcoidosis (SAR I, n = 12); active sarcoidosis with new or progressing symptoms (SAR II, n = 19), active sarcoidosis with spontaneous remission (SAR III, n = 10), tuberculosis (TB, n = 12), hypersensitivity pneumonitis (HP, n = 12), Wegener's disease (WD, n = 2), undefined alveolitis (UA, n = 8) and chronic obstructive pulmonary disease (COPD, n = 6) by employing the histoincompatibility-insensitive Jurkat cells as indicator cells. RESULTS: Compared with the controls (1.08 +/- 0.3) AMs of all groups but SAR I (AI: 0.96 +/- 0.42) exhibited significantly increased AIs (SAR II: 3.6 +/- 3.9; SAR III: 3.2 +/- 2.4; TB: 2.8 +/- 2.2; HP: 3 +/- 2; UA: 2.7 +/- 2.3; COPD: 3.1 +/- 2.2; p < 0.05 for all comparisons). Only in HP, AI of PBM was significantly increased compared with controls (3 +/- 1.5, 1.3 +/- 0.5, respectively; p < 0.001). Alveolar macrophages from patients with arcoidosis, TB, and HB express the costimulatory molecule CD80 on their surface and anti-CD80 antibodies inhibited the IL-2 release of Jurkat cells in this system to 59 +/- 27%. CONCLUSIONS: Our data demonstrate that AM from patients with various diseases have the capability to act as competent accessory cells and that the reported accessory function of these cells is at least in part mediated by the expression of CD80.

Adult↗
PubMed1997

Spontaneous and interleukin-2-modulated cytokine release by bronchoalveolar cells in pulmonary malignancy.

In a recent phase I study of inhalative, human natural interleukin-2 (hnIL-2) treatment of pulmonary metastases from previously resected solid tumors (mainly renal carcinoma), we have reported that this treatment resulted in an increased accessory function of alveolar macrophages (AM) [1]. Encouraged by these data, we investigated the influence of hnIL-2 inhalation on proinflammatory cytokines spontaneously released by AM. Bronchoalveolar lavage was performed in four groups, each of four patients, before and after 2 weeks of daily inhalation of 0, 200,000, 600,000 and 1,200,000 IU of hnIL-2, respectively. Bronchoalveolar cells were cultured without stimulation to allow spontaneous release over a period of 24 h, into the supernatant. Concentrations of tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8 and macrophage inflammatory protein-1alpha (MIP-1alpha) were determined by the ELISA technique. Before hnIL-2 inhalation, we measured the following spontaneous cytokine release: TNF-alpha: 1,115.4 +/- 469.1 pg/ml, IL-6: 267.5 +/- 67.7 pg/ml cells, IL-8: 137.8 +/- 40.5 ng/ml, MIP-1alpha: 9.5 +/- 6.8 ng/ml. Inhalation of hnIL-2 did not result in any significant changes in these cytokines. Comparing TNF-alpha release in healthy controls (250.6 +/- 46.7 pg/ml) with that of tumor patients (1,115.4 +/- 469.1 pg/ml), we observed significantly (p < 0.05) elevated TNF-alpha levels in the patient group, which did not change significantly in response to IL-2 inhalation. Our data demonstrate that the activation of AM previously observed after hnIL-2 inhalation is not directly related to a hnIL-2-induced cytokine release by bronchoalveolar cells.

Adult↗
PubMed1996

[Differential diagnosis of berylliosis/sarcoidosis in a dental technician].

HISTORY AND CLINICAL FINDINGS: Sarcoidosis was diagnosed in a dental technician when he was aged 21 years. Two years later prednisolone treatment was started and continued for 14 years because of nonproductive cough with progressive reduction in vital capacity and CO transfer capacity. Subsequently the risk of exposure to beryllium-containing dust in dental laboratories became known. In his case exposure had started before sarcoidosis had been diagnosed and had continued for 16 years. Changes typical of sarcoidosis (unproductive cough and dyspnoea; bihilar lymphadenopathy and reticulonodular marking in the chest radiogram) were now present, at the age of 40 years. INVESTIGATIONS: Vital and diffusion capacities were diminished, serum levels of angiotensin-converting enzyme (141 U/I) and of neopterin (5.8 mg/l) were increased. Beryllium-lymphocyte transformation test of peripheral mononuclear cells after invitro culture with beryllium sulphate gave a raised stimulation index, and the intracutaneous beryllium sensitisation test was positive. This indicated sensitisation to beryllium even 9 years after exposure had ceased. CONCLUSION: Even after exposure to beryllium has ended, proof of exposure together with clinical and radiological findings typical of sarcoidosis and beryllium sensitisation can provide the diagnosis of berylliosis.

Adult↗
PubMed1996

Spontaneous interleukin 2 release of bronchoalveolar lavage cells in sarcoidosis is a codeterminator of prognosis.

There is mounting evidence that activated interleukin 2 (IL-2)-releasing lymphocytes play a central role in the immunopathogenesis of sarcoidosis by directing inflammatory reactions and granuloma formation. In the context that a significant proportion of these cells accumulates in the lung and releases mediators, we hypothesized that different immunologically defined stages of sarcoidosis can be identified. A cohort of 89 sarcoidosis patients was allocated to four groups according to the following criteria: stage A, a low number of bronchoalveolar lavage (BAL) lymphocytes (< 20%) without IL-2 release (< 1 unit/ml in BAL cell culture supernatant); stage B, BAL lymphocytes < 20%, with IL-2 release (> or = 1 unit/ml); stage C, BAL lymphocytes > or = 20% with IL-2 release; and stage D, > or = 20% BAL lymphocytes without IL-2 release. Although patients of stages C and D (n = 49) exhibited lymphocytic inflammation, only 20/49 of these patients had activated IL-2-releasing alveolar lymphocytes. BAL of groups A and B showed a low number of lymphocytes, but the lymphocytes were activated in 20/40 patients. Forty-four patients not receiving therapy were reevaluated by pulmonary function tests 8 +/- 1 months after BAL. Progressive disease was found in 9/12 patients of group C and stable or regressing disease in 13/13 patients of group A. These results demonstrate that a combination of BAL parameters can yield prognostic information.

Adult↗
PubMed1996

Induction of accessory cell function of human alveolar macrophages by inhalation of human natural interleukin-2.

Accessory function allows antigen-presenting cells to produce sufficient secondary signals for optimum T cell proliferation and interleukin-2 (IL-2) production. Alveolar macrophages are inferior accessory cells compared to monocytes (PBM). We report here that the accessory index (AI) of alveolar macrophages and PBM of patients with lung metastases of solid tumors treated with inhalations of human natural IL-2 (hnIL-2) increased following its administration (P<0.005). The accessory index was significantly elevated from baseline values after 2 weeks of inhalation of 300,000 IU hnIL-2/day (8.2 +/- 10.2 compared to 1.1 +/- 1; P<0.001). The inhalation of 150,000 IU also induced increases in the index (AI = 2.3 +/- 1.9), however, without reaching statistical significance. In addition at 300000 IU IL-2/day a significant increase in the accessory index was observed for PBM (4 +/- 2.5; P<0.05). The indices of PBM and alveolar macrophages prior to inhalation showed a significant negative correlation with the age of the patients (r(s) = -0.5; r(s) = -0.8, respectively; P<0.03 for all comparisons). Our data demonstrate that the inhalational application of hnIL-2 enhances the accessory function of alveolar macrophages and, to lesser extent, the accessory index of PBM, indicating the occurrence of pharmacological immunostimulation.

Administration, Inhalation↗