Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, with the aging of patients with pneumoconiosis, autoimmune diseases as a complication have been observed. One of the reasons for this may be that autoimmune diseases are prone to develop among the elderly. On the other hand, it has been reported that dust itself, such as silica for example, has adjuvant effect. A review of the recent literature published in Japan and abroad was made to clarify the relationship between pneumoconiosis and autoimmune diseases and the following results were obtained. 1) Disorders which accompany pneumoconiosis: Scleroderma, rheumatoid arthritis, systemic lupus erythematosus (SLE), and disorders of the kidney and liver have been reported. In Japan, about 30 cases of pneumoconiosis accompanied with autoimmune diseases have been reported. In many of the reports, patients with pneumoconiosis and scleroderma have a past history of exposure to silica. In both case studies and case control studies, patients with rheumatoid arthritis and history of silica exposure are prone to develop pneumoconiosis. 2) Immunological studies of patients with pneumoconiosis: As for humoral immunity, elevation of polyclonal gamma-globulin, especially IgG, has been often reported together with high positive rate of autoantibodies such as antinuclear antibodies. In cellular immunity, decreased delayed type skin reaction and decreased CD4/8 ratio have been reported. In human leukocyte antigen (HLA) typing the elevated frequency of DR4 has been reported. In the study of BAL increased production of superoxide anion O2- by alveolar macrophages has been observed. 3) EXPERIMENTAL STUDIES: Silica is well known for its toxicity to cells and also for its adjuvant effect. In the German Democratic Republic, patients with scleroderma and history of long term silica exposure are recognized as patients with occupational disease even though pneumoconiosis is not clearly demonstrated on X-ray film. It is difficult from this review to nrake a definite conclusion regarding the relation between silicosis and autoimmune diseases. There is a need to repeat this review of the literature on autoimmune diseases and pneumoconiosis in the near future.
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PMID:[Relationship between autoimmune diseases and pneumoconiosis]. 140 2

Leukocyte subsets in bronchoalveolar lavage (BAL) fluid and peripheral blood of patients with paraccoccidioidomycosis, sarcoidosis and silicosis were characterized using monoclonal antibodies and an immunoperoxidase technique. In paraccocidioidomycosis, the number of T-helper/inducer CD4-positive lymphocytes was lower in peripheral blood than in BAL fluid. Additional analysis showed that the expression of HLA-DR was very similar in alveolar macrophages, lung and blood T-cells. In sarcoidosis and silicosis there were higher proportions of T-helper/inducer cells in peripheral blood than in BAL fluid. The alterations in the T-helper/inducer/T-suppressor/cytoxic CD4/CD8 ratio in sarcoidosis and silicosis were more appreciable in peripheral blood than in BAL fluid, contrasting with the results in paracoccidioidomycosis. The expression of HLA-DR by alveolar macrophages in sarcoidosis was the highest of all the disease studied. No statistically significant differences were observed between chronic multifocal and chronic unifocal paracoccidioidomycosis disease, stage II and stage III sarcoidosis, and chronic and accelerated silicosis. The three granulomatous diseases analyzed had a few alveolar macrophages expressing the CD4 molecule on their surface. These findings and the technique of analyzing both peripheral blood and BAL leukocyte subsets may help to understand the pathogenesis of interstitial lung diseases.
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PMID:Leukocyte immunophenotypes in bronchoalveolar lavage fluid and peripheral blood of paracoccidioidomycosis, sarcoidosis and silicosis. 183 75

The impact of human immunodeficiency virus (HIV) infection on Mycobacterium kansasii disease in miners was investigated with a retrospective study covering a single workforce. M. kansasii, isolated from 43 HIV-positive and 202 HIV-negative miners, was the most common nontuberculous mycobacterial (NTM) species in both HIV groups. CD4 counts were unusually high for M. kansasii disease (mean 490 x 10(6)/L, from 14 HIV-positive men). Treatment outcomes were similar: mortality during treatment was higher in HIV-positive than in HIV-negative men (9% and 2%, respectively), but not significantly so. The majority of a sample of 31 HIV-positive and 92 HIV-negative men had radiological silicosis and/or old tuberculosis scarring prior to M. kansasii disease. A normal premorbid radiograph was more common in HIV-positive men (45% versus 24%; odds ratio [OR], 2.62; 95% confidence interval [95% CI], 1.01 to 6.67). New cavitation was less common (55% versus 78%; OR, 0.34; 95% CI, 0.13 to 0.88) and new hilar adenopathy more common (OR, 5.07; 95% CI, 1.24 to 21.9) in HIV-positive than in HIV-negative men. Miners, who have additional NTM risk factors, develop M. kansasii disease that occurs at an earlier stage of HIV infection and more closely resembles disease in HIV-negative men than has been found for HIV-associated M. kansasii disease in other settings.
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PMID:The impact of HIV infection on Mycobacterium kansasii disease in South African gold miners. 1039 Mar 73

We describe a fatal case of accelerated silicosis with a component of mixed-dust pneumoconiosis in a young hard-metal grinder that we believe is the first case of its kind in Israel and one of the rare cases reported worldwide. The patient's diagnosis was based on typical features: restrictive lung function, abnormal chest roentgenogram suggesting lung fibrosis, a history of exposure to silica and hard metals, bronchoalveolar lavage (BAL) fluid findings, and mineralogical studies. BAL cells showed an abundance of giant multinucleated macrophages. The CD4/CD8 ratio of T lymphocytes was 1.1, with a high percentage of CD8 and CD8/38 positive cells (37% suppressor/cytotoxic and 12% cytotoxic T lymphocytes, respectively). mRNA transcripts isolated from BAL cells were positive for interleukin-1 (IL-1) and transforming growth factor (TGF) Il-5, IL-2, and IL-10 but not for IL-6, IL-4, and interferon. Polarizing light microscopic studies of BAL and induced sputum cells showed polarizing particles, which are typical for silica. Mineralogical studies of electron microscopy performed on BAL fluid and on dust collected at the patient's workstation revealed silica particles as well as aluminum-titanium and other particles. The latter might have contributed to the patient's lung disease.
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PMID:Accelerated silicosis with mixed-dust pneumoconiosis in a hard-metal grinder. 1039 Jun 99

The aim of this study was to determine risk factors for disease due to nontuberculous mycobacteria (NTM) compared to those due to Mycobacterium tuberculosis in South African gold miners with pulmonary mycobacterial disease. A case/control study comparing tuberculosis and NTM cases amongst all patients with a positive sputum mycobacterial culture in 1995 was carried out. The 51 cases of disease due to NTM and 425 tuberculosis cases were similar with regard to age, education, home region, smoking habits and percentage of CD4 cells. After adjustment for confounders, those with NTM were more likely to have had previous tuberculosis treatment (odds ratio (OR) 3.61; 95% confidence interval (CI) 1.9-6.9), have worked longer underground (p-value for trend=0.05) or have evidence of silicosis (OR 12.6; 95% CI 2.2-71) and were less likely to drink regularly (OR 0.12; 95% CI 0.02-0.93) than patients with tuberculosis. In patients with disease due to NTM, 35.3% were human immunodeficiency virus-positive compared with 48.8% of tuberculosis patients (p=0.2) and an estimated 21% overall in the mines at the time of the study. Previous tuberculosis treatment, silicosis and duration of underground work are even more strongly associated with disease due to nontuberculous mycobacteria than with tuberculosis. Attempts to reduce the incidence of all pulmonary mycobacterial disease in this community should address recognized risk factors and ensure that those with tuberculosis are diagnosed, treated and cured.
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PMID:Risk factors for pulmonary disease due to culture-positive M. tuberculosis or nontuberculous mycobacteria in South African gold miners. 1070 94

We recently described overproduction of interferon (IFN)-gamma by lung lymphocytes in mice with silicosis (11% of cells in air-control versus 19% of cells from silica-exposed mice; Davis and colleagues, Am. J. Respir. Cell Mol. Biol. 1999;20:813-824). We hypothesized that the increased IFN-gamma production might be due to selective enrichment of one lymphocyte phenotype. To test this hypothesis, small mononuclear cells from lung digest preparations of mice exposed 4 mo previously to cristobalite silica (70 mg/m(3), 12 d, 5 h/d) or to sham-air were stained for intracellular cytokines and surface antigen phenotypes, and examined by flow cytometry. Air-sham mouse lung digests included CD4(+) (16%) and CD8(+) (6%) T cells, gammadelta T-cell antigen receptor (TCR)(+) CD4(-)CD8(-) T cells (3%), natural killer (NK) cells (15%), B cells (6%), and macrophages (12%). The total number of lung lymphocytes was increased 1.7-fold in silicosis, but the phenotype frequencies did not change significantly. In the control lungs IFN-gamma was produced by three major phenotypes of lymphocytes: 5% of CD4(+) T cells, 5% of gammadelta-TCR(+) CD4(-)CD8(-) T cells, and 2% of NK cells. The percentage of each type producing IFN-gamma was increased 2- to 3-fold in silicosis. When multiplied by cell number, the increased percentages yielded a 3- to 5-fold increase in the total number of each IFN- gamma-producing phenotype in the lung. Our results demonstrate no selective phenotype enrichment but upregulated IFN-gamma production by at least three lymphocyte phenotypes. IFN-gamma may be an important signal driving lymphocyte differentiation and macrophage activation in silicosis.
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PMID:Interferon-gamma production by specific lung lymphocyte phenotypes in silicosis in mice. 1074 30

Silicosis is characterized by mononuclear cell aggregation with mineral particles and fibrosis. Lymphocytes are abundant in these lesions. We exposed inbred strains of mice to a respirable aerosol of cristobalite silica (70 mg/m3, 5 h/d, 12 d) or shamair. Silicosis evolved over months after exposure. The silica-exposed mice showed the accumulation of lymphocytes in alveolar spaces (seen in bronchoalveolar lavage), in lung parenchymal lesions and nodules, and in enlarged bronchial-associated lymphoid tissues and thoracic lymph nodes. The lung lymphocytes were predominantly CD4+ T cells, but numerous CD8+ T cells, natural killer cells, and CD4- gammadelta-TCR+ T cells were present as well. Interferon-gamma (IFN-gamma) production was upregulated, suggesting a THelper-1-like response in silicosis. In silicotic lung tissue, mRNA transcripts for the macrophage-derived cytokines IL-12 and -18 were increased. IFN-gamma gene-deleted mice (C57Bl/6-Ifngtm1 Ts) exposed to silica developed less extensive silicosis and less lung collagen accumulation than wild-type mice. We hypothesize that there is a reiterative amplification cycle in which macrophages with silica may produce cytokines, such as IL-12 and -18, that attract and activate lymphocytes. These activated lymphocytes may then produce additional mediators that in turn attract and activate an expanded secondary population of macrophages. IFN-gamma would be a likely cause of macrophage activation in this cycle. More work is needed to understand the biological events that lead from the inhaled dust to the scarred lung, and to clarify the role of lymphocytes in this process.
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PMID:Lymphocytes, lymphokines, and silicosis. 1157 Jun 74

We investigated immunopathogenic roles for apoptosis in acute murine silicosis. Intratracheal silica instillation induced pulmonary inflammation and enlarged thoracic lymph nodes. Lymphocytes from silica-exposed lymph nodes showed reduced mitogenic responses to T cell receptor (TCR) stimulation, and markedly increased activation-induced cell death, compared with control lymphocytes from saline-exposed lymph nodes. CD4(+) T cell death was mediated by Fas ligand, because CD4(+) T cells from Fas ligand-deficient gld mice did not undergo activation-induced apoptosis. Silica deposition also resulted in increased apoptosis associated with inflammatory infiltrates in lung parenchyma. In vivo treatment with caspase inhibitors reduced neutrophil accumulation, and alleviated inflammation in the lungs of silica-treated mice. These results suggest that silica-induced apoptosis plays an inflammatory role in the lung parenchyma, and creates immunologic abnormalities in regional lymph nodes, with pathogenic implications for the host.
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PMID:Apoptosis underlies immunopathogenic mechanisms in acute silicosis. 1209 Dec 49

We previously described a reduction of silica-induced lung fibrosis in interleukin-10-deficient mice (IL-10-/-) (Huaux and colleagues; Am. J. Respir. Cell Mol. Biol. 1998;18:51-59). In the present study, we further dissect the exact functions of IL-10 in experimental silicosis. The reduced lung fibrotic response to silica in IL-10-/- mice was accompanied by a marked recruitment of TH1 CD4+ lymphocytes. However, treatment with anti-CD4 antibodies reduced silica-induced lung fibrosis in both IL-10-/- and IL-10+/+ mice, suggesting that this T cell population actually contributes to the extension of the fibrotic lesions in a manner that is independent of IL-10. In IL-10-/- mice, silica-induced lung production of the profibrotic mediator transforming growth factor (TGF)-beta1 and the antifibrotic eicosanoid PGE2 were reduced and increased, respectively, relative to that in IL-10+/+ mice. In addition, in vitro experiments indicated that recombinant IL-10 upregulated TGF-beta1 expression in alveolar macrophages while in contrast it downregulated PGE2 production and cyclooxygenase-2 expression in both lung fibroblasts and macrophages. Thus the net profibrotic activity of IL-10 in vivo appears to be mediated by its ability to stimulate the expression of the profibrotic cytokine TGF-beta1 while suppressing the expression of cyclooxygenase-2 and thus production of the antifibrotic eicosanoid PGE2. These effects appear to be independent of the enhanced lung CD4+ T-lymphocytosis observed in IL-10-deficient mice.
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PMID:Characterization of the effect of interleukin-10 on silica-induced lung fibrosis in mice. 1497 40

IL-17-producing T lymphocytes play a crucial role in inflammation, but their possible implication in fibrosis remains to be explored. In this study, we examined the involvement of these cells in a mouse model of lung inflammation and fibrosis induced by silica particles. Upregulation of IL-17A was associated with the development of experimental silicosis, but this response was markedly reduced in athymic, gammadelta T cell-deficient or CD4(+) T cell-depleted mice. In addition, gammadelta T lymphocytes and CD4(+) T cells, but not macrophages, neutrophils, NK cells or CD8 T cells, purified from the lungs of silicotic mice markedly expressed IL-17A. Depletion of alveolar macrophages or neutralization of IL-23 reduced upregulation of IL-17A in the lung of silicotic mice. IL-17R-deficient animals (IL-17R(-/-)) or IL-17A Ab neutralization, but not IL-22(-/-) mice, developed reduced neutrophil influx and injury during the early lung response to silica. However, chronic inflammation, fibrosis, and TGF-beta expression induced by silica were not attenuated in the absence of IL-17R or -22 or after IL-17A Ab blockade. In conclusion, a rapid lung recruitment of IL-17A-producing T cells, mediated by macrophage-derived IL-23, is associated with experimental silicosis in mice. Although the acute alveolitis induced by silica is IL-17A dependent, this cytokine appears dispensable for the development of the late inflammatory and fibrotic lung responses to silica.
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PMID:IL-17A-producing gammadelta T and Th17 lymphocytes mediate lung inflammation but not fibrosis in experimental silicosis. 2042 47


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