Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease caused by bronchial colonization with Aspergillus fumigatus that affects approximately 10% of patients with cystic fibrosis (CF). The diagnosis in CF patients is difficult because the cardinal symptoms of ABPA occur frequently in CF, ie, pulmonary infiltrates and wheezing, as well as the frequent colonization with A fumigatus that leads to humoral reactivity. If left untreated, ABPA leads to bronchiectasis and pulmonary fibrosis. The pathogenesis of ABPA seems to be a prolonged asthmatic late-phase reaction orchestrated by CD4+ Th2-like T cells in response to persistent pulmonary A fumigatus allergen exposure. Thus, polyclonal and A fumigatus-specific IgE antibodies (and IgA and IgG) and blood pulmonary eosinophilia are stimulated by Th2-derived cytokines such as IL-4 and IL-5. In addition, IL-4 would also promote pulmonary transendothelial migration of eosinophils, basophils, and lymphocytes via induction of cell adhesion molecules and their ligands. IgE mast cell interactions would also contribute to the bronchial reactivity and inflammation. Recent advances have begun to identify immunodominant A fumigatus allergens. Evaluation of the quantity of IgE antibodies (and IgA and IgG) and T-cell cytokine responses to specific A fumigatus allergens should aid in the diagnosis and immunopathogenesis of ABPA, especially in CF patients.
 ...
PMID:Allergic bronchopulmonary mycosis complicating cystic fibrosis. 147 42

Evidence is accumulating that cytokines are important intermediates in the pathogenesis of many diseases such as asthma and pulmonary fibrosis. However, a major limitation to clinical studies of cytokines has been the inability to measure these important biomarkers in serum from normal, healthy controls. Without this capability, interpretation of apparently elevated levels in problematic, and evaluation of diseased level is impossible. We have recently developed chemiluminescence ELISA (CL-ELISA), resulting in a 100-fold increase in sensitivity. To assess the influence of age, smoking, and race on serum cytokine levels in healthy population, we measured IL-4, 5, 6, 10, IFN-gamma, and GM-CSF in serum of healthy Japanese (n = 38), and Americans (n = 10) using CL-ELISA. In this small population with narrow age range, no difference between smokers and nonsmokers was found for any cytokine. No correlations between age and cytokines was demonstrated. However, Japanese samples had lower levels of IL-4, 5, and 10 than American samples. Further evaluation using more controlled study design and larger populations will be necessary to determine whether this difference is due to inherent racial differences in Th2 cell function.
 ...
PMID:[Chemiluminescence assays for cytokines in serum: influence of age, smoking, and race in healthy subjects]. 757 31

Paraquat (PQ) is a herbicide which is highly pneumotoxic by generating reactive oxygen intermediates (ROI). Pro-inflammatory cytokines, particularly IL-1 and TNF, have been implicated in some ROI-mediated pathologies, including bleomycin toxicity and ischaemia/reperfusion injury. We have studied the effect of PQ on the expression of the neutrophil chemotactic cytokine, IL-8, by human peripheral blood mononuclear cells (PBMC). While almost no IL-8 mRNA was detected in unstimulated cells, PQ (100 microM) induced high mRNA expression with a maximum at 24 h of incubation. While PQ did stimulate the appearance of IL-8 mRNA, no significant production of IL-8 protein was detected. However, PQ potentiated the production of IL-8 in the presence of 1 ng/ml of endotoxin (lipopolysaccharide, LPS). This was paralleled by an increased production of chemotactic activity for neutrophils, indicating that the IL-8 was actually bioactive. Stimulation of IL-8 mRNA by PQ was suppressed by IL-4 and by free radical scavengers (dimethylsulfoxide, mannitol). Increased IL-8 expression by PQ was also observed in the human pulmonary epithelial cell line A549 indicating that the effect of PQ was not specific for PBMC. These findings suggest that IL-8 might be involved in the pulmonary effects of PQ and that its production might be stimulated following an oxidative insult, and might clarify the pathogenetic mechanisms of adult respiratory distress syndrome (ARDS) or oxidant-induced pulmonary fibrosis.
 ...
PMID:The pneumotoxicant paraquat induces IL-8 mRNA in human mononuclear cells and pulmonary epithelial cells. 814 10

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease characterized by Aspergillus fumigatus (Af) colonization, IgE and IgG anti-Af antibodies, pulmonary infiltrates, bronchiectasis, and pulmonary fibrosis. Little is known regarding T cell responses and their role in the pathogenesis of ABPA. To examine T cell reactivity to Af antigens, T cell clones (TCC) specific to the Asp f 1 antigen, an 18-kD protein of Af, were established from the peripheral blood of three ABPA patients. The majority of TCC isolated from ABPA patients, and specific for the Asp f 1 allergen of Af, are IL-4 producing CD4+ cells of the Th2 phenotype. Further analysis in this study revealed that the majority of TCC reacted to mainly two epitopes of Asp f 1, while the remaining TCC reacted to three additional "minor" epitopes. Blocking studies using monoclonal antibodies specific for class II HLA-D region gene products showed that most TCC, 19/21, were restricted by HLA-DR molecules, and the remaining two clones by HLA-DP molecules. The use of a panel of HLA-matched and mismatched EBV-transformed B cells as antigen presenting cells revealed that the HLA-DR restriction was mediated exclusively by either the HLA-DR2 or HLA-DR5 alleles. Genotyping of DRB1 gene products showed that class II presentation for most clones was not restricted to a single allele, representing DRB1 gene products of either HLA-DR2 or DR5. These studies offer insight into the cellular and molecular determinants which contribute to the immunopathophysiology of ABPA.
 ...
PMID:T cell subsets, epitope mapping, and HLA-restriction in patients with allergic bronchopulmonary aspergillosis. 863 13

Acute lung injury was produced in C57BL/6 mice by the intratracheal (i.t.) administration of bleomycin (BLM). Following injection of 0.1 U BLM, CD3+ lymphocytes and the production of the T-helper-1 (Th1) lymphokines interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were increased in lung and lymph nodes. The production of the Th2 cytokine IL-4 by lung lymphocytes was decreased. Intraperitoneal (i.p.) injection of a rat antimurine CD3 (YCD3) monoclonal antibody (mAb) blocked the accumulation of pulmonary CD3+ cells for up to 14 d and effectively suppressed IL-2 and IL-4 but not IFN-gamma production by lung lymphocytes throughout the protocol. Secretion of all of the above lymphokines by lymph node cells was inhibited by YCD3 treatment. Administration of YCD3 diminished pulmonary fibrosis and increased survival (p < 0.01) following BLM administration compared with mice treated with an isotype-matched control mAb. Initiating treatment with YCD3 at Days 5-7 following BLM also decreased pulmonary fibrosis and significantly reduced mortality (p < 0.02). We conclude that BLM yields a potentially lethal fibroinflammatory response in the lung that is markedly diminished by antagonizing the functional activities of CD3+ cells in vivo.
 ...
PMID:The effect of an anti-CD3 monoclonal antibody on bleomycin-induced lymphokine production and lung injury. 868 Jun 80

To examine the mechanism of steroid resistance in lung fibrosis, cytokines expressed in the lung tissue of mice with bleomycin-induced lung fibrosis were studied. 1. Glucocorticoid administration (1 mg/kg/day) did not affect the grade of lung fibrosis induced by intratracheal injection of bleomycin (3.76 micrograms/g). 2. Cytokines expressed in the lung tissue were studied with the reverse-transcriptase polymerase chain reaction. Levels of promotor cytokines, such as TNF alpha, TGF beta, INF gamma, and IL-2, were significantly higher in lung tissue from the bleomycin group. The expression of these cytokines in the glucocorticoid group was low, especially the peak value. Expression of IL-4 was high in the bleomycin group, and was not inhibited in the glucocorticoid group. Expression of the down-regulator cytokine IL-10 was also high in the bleomycin group and very low in the glucocorticoid group. 3. The non-selectivity of glucocorticoids with respect to promotor and suppressive cytokines may account in part for steroid resistance in bleomycin-induced pulmonary fibrosis.
 ...
PMID:[Steroid resistance and lung-tissue cytokines in experimental bleomycin-induced lung fibrosis]. 934 Dec 82

Cryptogenic fibrosing alveolitis (CFA), extrinsic allergic alveolitis (EAA), and sarcoid are all immunologically mediated forms of interstitial lung disease. In contrast to most patients with EAA and sarcoid, patients with CFA show relentless pulmonary fibrosis which is unresponsive to immunosuppressive therapy. Previous studies have indicated a possible role for epithelial-derived cytokines in the regulation of immunological and fibrotic responses in the lung. This study has examined lung biopsy specimens from patients with CFA, EAA, and sarcoid for immunoreactive interleukin 4 (IL4) and interferon-gamma (INFgamma) expression by type II alveolar epithelial cells, as these cytokines have been suggested to have in vitro stimulatory and inhibitory effects on fibroblast function. In addition, mRNA in situ hybridization was performed on the CFA lung biopsies to confirm transcription of these cytokine genes within the cells. The results show that type II epithelial cells in EAA and sarcoid show up-regulation of immunoreactivity for both IL4 and INF-gamma, but that in CFA only IL4 is detectable. The mRNA in situ hybridization results indicate that this may represent post-transcriptional regulation of INFgamma expression in CFA. These results are consistent with previous observations of a paucity of INFgamma and a predominantly type II (Th2-like) pattern of immune response in patients with CFA and suggest a possible imbalance of pro-fibrogenic cytokines in the distal lung of patients with this condition, compared with those with EAA or sarcoid.
 ...
PMID:Immunoreactive interleukin 4 and interferon-gamma expression by type II alveolar epithelial cells in interstitial lung disease. 1039 9

As variable functions of cytokines have been proved in recent years, cytokine levels in biological fluids such as serum, plasma, and synovial fluid of patients with every kind of disease have been enthusiastically measured. As a result, many studies have shown an increase or decrease in the production of cytokines or abnormal cytokine levels in biological fluids. However, the relationship between the abnormal levels of cytokines and the intensity of the clinical symptoms or the prognosis remains unclear. The significance for the measurement of cytokines depends on whether it should be valid for detecting a preclinical status such as AST or ALT used for health checks or for disease screening such as some tumor markers. The purpose of this study is to know whether or not some cytokine levels in serum could be biomarkers for preventive purposes. Serum cytokine levels (IL-4, 6, 8, 12, and IFN-gamma) were measured in three different types of cohorts (nursery school infants, manufacturing workers and middle and old aged women) with chemiluminescence ELISA. The results showed no differences with atopic status in infants, pulmonary fibrosis in workers or with the decrease in bone stiffness, these results are mainly due to a great inter-individual variability of serum cytokine levels. This study concludes that serum cytokine levels are inappropriate as biomarkers for preventive purposes. However, a further detailed evaluation in healthy people with high serum cytokine levels may be necessary.
 ...
PMID:[The public health significance of the measurement of cytokines in serum]. 1071 50

Anaphylaxis represents an extreme form of allergic reaction. This acute-phase component of allergy and asthma is triggered by allergen-induced degranulation of mast cells following the cross-linking of cell surface-bound, allergen-specific IgE, resulting in the liberation of inflammatory mediators and the development of bronchoconstriction. We used IL-13 transgenic mice to investigate the role of this Th2 cell-derived cytokine in the onset of allergic disease. Strikingly, IL-13-transgenic mice were highly predisposed to fatal anaphylaxis following Ag sensitization. This response correlated with substantially elevated levels of circulating Ag-specific IgE, mast cell degranulation, and histamine release. Furthermore, allergen exposure also induced phenotypic changes typical of asthma, including pulmonary fibrosis, goblet cell hyperplasia, elevated Th2 cytokines, eosinophilia, and airways occluded by mucus and Charcot-Leyden crystals. Expression of IL-4 was not required for the induction of IgE-mediated responses. These data represent the first characterization of a functional role for IL-13-induced IgE in the generation of immediate hypersensitivity reactions and highlight the importance of IL-13 in the development of the symptoms of atopy. The systemic regulation of this response makes these mice an important resource for studying atopic responses.
 ...
PMID:IL-13 overexpression predisposes to anaphylaxis following antigen sensitization. 1116 Mar 36

We examined the effect of interleukin (IL)-9, a cytokine active on B and T lymphocytes and associated with bronchial asthma, on the development of lung fibrosis induced by crystalline silica particles. Therefore, we compared the response to silica (1 and 5 mg/animal, intratracheally) in transgenic mice that constitutively express high levels of IL-9 (Tg5) and their wild-type counterparts (FVB). At 2 and 4 mo after treatment with silica, histologic examination and measurement of lung hydroxyproline content showed that the severity of fibrosis was significantly less important in Tg5 mice than in their wild-type counterparts. Intraperitoneal injection of IL-9 in C57BL/6 mice also reduced the amplitude of silica-induced lung fibrosis. The reduction of lung fibrosis by IL-9 was associated with a significant expansion of the B-lymphocyte population, both in bronchoalveolar lavage (BAL) and in the pulmonary parenchyma. In wild-type animals, silica-induced fibrosis correlated with markers of a T helper 2-like response such as upregulation of IL-4 levels in lung tissue and an increased immunoglobulin (Ig) G1/IgG2a ratio in BAL. Immunohistochemical studies demonstrated that the upregulation of IL-4 associated with the development of fibrosis was mainly localized in inflammatory alveolar macrophages. In transgenic mice, the level of IL-4 in lung homogenates was not significantly affected by silica treatment, and a reduced IgG1/IgG2a ratio was observed upon treatment with silica. The levels of interferon-gamma were significantly decreased after silica treatment in both strains. Together, these observations point to an antifibrotic effect of IL-9 in pulmonary fibrosis associated with a limitation of the type 2 polarization which accompanies lung fibrosis.
 ...
PMID:Interleukin-9 reduces lung fibrosis and type 2 immune polarization induced by silica particles in a murine model. 1130 27


1 2 3 4 5 6 7 8 Next >>