Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: DrugBank:BIOD00017 (IFN-gamma)
28,919 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiopulmonary bypass (CPB) is associated with an inflammatory response, mainly caused by the trauma of surgery, contact of blood with the artificial surface of the circuit, and reperfusion injury, resulting in increased capillary permeability, respiratory distress, low cardiac output, and multiorgan failure. The inflammatory reaction includes an activation of the humoral and cellular immune system with enhanced release of cytokines. The present study focused on the effect of CPB on the time course of pro- and anti-inflammatory cytokines. In 20 patients undergoing coronary artery bypass grafting, the plasma concentration of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-2, IL-4, IL-6, IL-8, and IL-10 was investigated pre-, intra-, and postoperatively by enzyme-linked immunosorbent assay technique. With the exception of IFN-gamma, all the other cytokines could be detected in the patients plasma. However, neither TNF-alpha nor IL-1 beta and IL-2 revealed significant changes in concentration during the investigated time period. In contrast, IL-6 and IL-8 levels peaked early postoperatively, reaching median concentrations of 430 pg/ml (221 pg per ml/558 pg per ml; lower/upper quartiles, respectively) and approximately 12 pg/ml (0/17 pg/ml; lower/upper quartiles, respectively). IL-4 and IL-10, respectively, revealed maximal concentrations of approximately 2 pg/ml (0/39 pg/ml; lower/upper quartiles, respectively) and 208 pg/ml (76 pg per ml/380 pg per ml; lower/upper quartiles, respectively) immediately after protamine administration, preceding the maximal concentration of IL-6. The degree of the observed modulation of cytokine patterns during and after CPB seemed to be patient-dependent, since large interindividual variations in cytokine levels were observed, not only preoperatively, but especially during and following CPB. However, IL-6 and IL-10 showed the least interindividual variations, suggesting that these cytokines may give reliable information regarding modulation of the immune response following CPB and its consequences for the patient's outcome.
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PMID:Interindividual variations in cytokine levels following cardiopulmonary bypass. 949 62

The first fatal case caused by the new genome type 7i is described in an 8-month-old boy requiring long-term respiratory support who developed Reye's syndrome, acute respiratory distress, and bronchiolitis obliterans with fatal evolution. Adenovirus was detected in nasopharyngeal secretions and was persistently positive during hospitalization. IgM and IgG adenovirus antibody titers measured in serum by enzyme-linked immunoassay (EIA) were 1:32 and 1:800, respectively. Serum interleukins (IL) and interferons (IFN) measured by EIA were as follows: IL-2, 110 pg/ml; IL-6, 300 pg/ml; IL-8, 7,000 pg/ml; TNF-alpha, 35 pg/ml, IL-1 and IL-4 undetectable, IFN-alpha 2,200 pg/ml, and IFN-gamma 700 pg/ml. Virologic studies showed that adenovirus isolated belonged to subgenus B, and digestion of viral DNA with Bam HI, Sma I, Bgl II, and Hind III identified the isolate as belonging to genome type 7i. Autopsy showed bronchiolitis obliterans with diffuse alveolar damage and perivenular fatty degeneration with polymorphonuclear infiltrates in the periportal spaces. The difficulty in obtaining adequate oxygenation with minimization of iatrogenic oxygen injury is discussed.
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PMID:Fatal adenovirus infection associated with new genome type. 951 74

Respiratory syncytial virus (RSV) is the major cause of acute bronchiolitis in infancy, a syndrome characterized by wheezing, respiratory distress, and the pathologic findings of peribronchial mononuclear cell infiltration and release of inflammatory mediators by basophil and eosinophil leukocytes. Composition and activation of this cellular response are thought to rely on the discrete target cell selectivity of C-C chemokines. We demonstrate that infection in vitro of human epithelial cells of the lower respiratory tract by RSV induced dose- and time-dependent increases in mRNA and protein secretion for RANTES (regulated upon activation, normal T-cell expressed and presumably secreted), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1alpha (MIP-1alpha). Production of MCP-1 and MIP-1alpha was selectively localized only in epithelial cells of the small airways and lung. Exposure of epithelial cells to gamma interferon (IFN-gamma), in combination with RSV infection, induced a significant increase in RANTES production that was synergistic with respect to that obtained by RSV infection or IFN-gamma treatment alone. Epithelial cell-derived chemokines exhibited a strong chemotactic activity for normal human blood eosinophils. Furthermore, eosinophils were susceptible to RSV and released RANTES and MIP-1alpha as a result of infection. Therefore, the inflammatory process in RSV-induced bronchiolitis appears to be triggered by the infection of epithelial cells and further amplified via mechanisms driven by IFN-gamma and by the secretion of eosinophil chemokines.
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PMID:Cell-specific expression of RANTES, MCP-1, and MIP-1alpha by lower airway epithelial cells and eosinophils infected with respiratory syncytial virus. 957 40

Inhaled endotoxin (lipopolysaccharide, LPS) can induce acute lung injury and at high doses may lead to respiratory distress syndrome. Using a mouse model of acute lung inflammation induced by inhalation of low doses of LPS we examined the kinetics of chemokine, proinflammatory cytokine, and metallothionein. Eight-week-old C57BL/6 mice were dosed for 10 min with LPS, resulting in an estimated alveolar dose of < 10 ng LPS/mouse, and euthanized 2,6, or 24 h postexposure. Analysis of bronchoalveolar lavage fluid demonstrated increased polymorphonuclear neutrophils (PMNs) of 6.94, 32.7, and 38.8% after 2, 6, and 24 h, respectively. Examination of proinflammatory cytokine, chemokine, and Mt mRNA in the lung revealed increases for messages encoding IL-1 alpha, IL-1 beta, IL-6, IFN-gamma, TNF alpha, Eotaxin, MIP-1 alpha, MIP-1 beta, MIP-2, Mt, and IP-10, while messages encoding IL-12, IL-10, IFN-beta, Ltn, MCP-1, TGF beta 1 + 2, and RANTES were unchanged from those of sham-exposed mice 2 h postexposure. By 6 h most messages had returned to near control levels. Comparison to 5 mg/kg body weight intraperitoneal injection and 5 micrograms/mouse intratracheal instillation 2 h postexposure demonstrated similar message responses. Our results demonstrate that low levels of LPS exposure by inhalation induce a strong PMN response and a selective cytokine response in the lung, supporting the hypothesis that PMNs may regulate inflammatory processes via cytokine and chemokine response.
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PMID:Pulmonary cytokine and chemokine mRNA levels after inhalation of lipopolysaccharide in C57BL/6 mice. 1004 33

Intra-amniotic lipopolysaccharide (LPS) and cytokines may decrease respiratory distress syndrome (RDS) and increase chronic lung disease in the newborn. The aim was to identify the primary inflammatory mediators regulating the expression of surfactant proteins (SP) in explants from immature (22-day-old fetus) and mature (30-day term fetus and 2-day-old newborn) rabbits. In immature lung, interleukin (IL)-1alpha and IL-1beta upregulated the expression of SP-A and SP-B. These effects of IL-1 were diminished, and SP-C mRNA was suppressed additively in the presence of tumor necrosis factor (TNF)-alpha and either LPS or interferon (IFN)-gamma. LPS, TNF-alpha, or IFN-gamma had no effect alone. In explants from the term fetus and the newborn, LPS, IL-1alpha, and TNF-alpha additively suppressed the SPs. LPS acutely induced IL-1alpha in alveolar macrophages in mature lung but not in the immature lung. IFN-gamma that generally has low expression in intrauterine infection decreased the age dependence of the other agonists' effects on SPs. The present study serves to explain the variation of the pulmonary outcome after an inflammatory insult. We propose that IL-1 from extrapulmonary sources induces the SPs in premature lung and is responsible for the decreased risk of RDS in intra-amniotic infection.
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PMID:Regulation of surfactant proteins by LPS and proinflammatory cytokines in fetal and newborn lung. 1188 Mar 7

Apoptosis is thought to be involved in lung epithelial cell damage in acute respiratory distress syndrome and interstitial pneumonia. Both the role of apoptosis and its underlying molecular mechanisms in human lung tissue remain unclear. To address these issues, we developed an in vitro assay in which a human lung epithelial cell line and a staphylococcal enterotoxin B (SEB)-reactive human CD8(+) CTL line were co-cultured in the presence of SEB. SEB-stimulated CD8(+) CTL induced apoptosis in the lung epithelial cell line primarily through the perforin/granzyme-mediated pathway. In these cells, apoptosis was initially independent of death receptor pathways. We also tested the effect of IFN-gamma on modulation of apoptosis in lung epithelial cells. In IFN-gamma-pretreated lung epithelial cells, CD95 (APO-1/Fas) activation as well as TNF-related apoptosis-inducing ligand (TRAIL) receptor and TNFR activation led to apoptosis. Furthermore, we found that the interaction of SEB-stimulated CD8(+) CTL with lung epithelial cells induced an increase in TNF-alpha secretion. These results suggest an important role for bacterial superantigen-reactive CD8(+) CTL in induction of lung epithelial cell apoptosis and in modulation of inflammatory processes in lung tissue.
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PMID:Activated T killer cells induce apoptosis in lung epithelial cells and the release of pro-inflammatory cytokine TNF-alpha. 1516 47

The alveolar compartment in acute lung injury contains high levels of tissue factor (TF) procoagulant activity favoring fibrin deposition. We previously reported that the alveolar epithelium can release TF procoagulant activity in response to a proinflammatory stimulus. To test the hypothesis that the alveolar epithelium further modulates intra-alveolar fibrin deposition through secretion of an endogenous inhibitor to TF, tissue factor pathway inhibitor (TFPI), we measured TFPI levels in edema fluid (EF) from patients with acute respiratory distress syndrome. To determine whether the alveolar epithelium can release TFPI, both full-length TFPI and truncated TFPI were measured (ELISA) in pulmonary edema fluid from patients with acute respiratory distress syndrome (ARDS) and a control group of patients with hydrostatic pulmonary edema (HYDRO). TFPI protein was also measured in conditioned media (CM) and cell lysates (CL) from human alveolar epithelial cells (A549) after exposure to cytomix (TNF-alpha, IL-1 beta, IFN-gamma). TFPI protein levels were higher in pulmonary edema fluid from patients with ARDS vs. HYDRO. TFPI protein was increased in CM and did not change in CL after cytomix treatment; TFPI mRNA levels (RT-PCR) did not change. Despite the high levels of TFPI, both the EF and CM retained significant TF procoagulant activity as measured by plasma recalcification time. The majority of intra-alveolar TFPI was in a truncated, inactive form, whereas the majority of TFPI released from cells was full length, suggesting different mechanisms of inactivation. In summary, the alveolar epithelium releases TFPI in response to an inflammatory stimulus but does not increase TFPI gene transcription or protein production. Levels of intra-alveolar TFPI in ARDS are not sufficient to block intra-alveolar TF procoagulant activity due to truncation and inactivation of intra-alveolar TFPI.
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PMID:Intra-alveolar tissue factor pathway inhibitor is not sufficient to block tissue factor procoagulant activity. 1831 Feb 27

The most dramatic example of defining the pathogenicity of influenza virus A/H5N1 strains is the higher fatality rate of avian influenza epidemic (>50%) occured in Southeast Asia in 1997 comparing to the pandemic caused by influenza virus A/H1N1 in 1918 (5-10%) which was recorded as the most destructive pandemic in the world. When considering the fatal/total case numbers (208/340) reported by World Health Organization in respect of December 14th, 2007, the mortality rate has now reached to 61 percent. Recent studies have shown that the high fatality rate of avian influenza virus infections is a consequence of an overactive inflammatory response and the severity of infection is closely related with virus-induced cytokine dysregulation. The most important feature of A/H5N1 immunopathogenesis is the appearence of hypercytokinemia ("cytokine storm") which is characterized by the extreme (exaggerated) production and secretion of large numbers and excessive levels of pro-inflammatory cytokines. This phenomenon is blamed on the emergence of lethal clinical symptoms such as extensive pulmonary oedema, acute bronchopneumoniae, alveolar haemorrhage, reactive haemophagocytosis, and acute respiratory distress syndrome, associated with necrosis and tissue destruction. Numerous in vitro, in vivo and clinical studies have pointed out that A/H5N1 viruses are very strong inducers of various cytokines and chemokines [Tumor Necrosis Factor (TNF)-alpha, Interferon (IFN)-gamma, IFN-alpha/beta, Interleukin (IL)-6, IL-1, MIP-1 (Macrophage Inflammatory Protein), MIG (Monokine Induced by IFN-gamma), IP-10 (Interferon-gamma-Inducible Protein), MCP-1 (Monocyte Chemoattractant Protein), RANTES (Regulated on Activation Normal T-cell Expressed and Secreted), IL-8], in both humans and animals. The privileged cells of cytokine storm are macrophages and CD8+ T-lymphocytes, while the primary contributor cytokines are TNF-alpha, IL-6 and IFN-gamma. It has been detected that, mutations of some viral genes (NS1, PB2, HA and NA) are responsible for the cytokine storm, by increasing the viral replication rate, expending the tissue tropism, facilitating the systemic invasion and emerging of resistance against the host antiviral response. It has been shown that Glu92 and Ala149 mutations, and carboxyl-terminal ESEV/EPEV motif of NS1 protein have been implicated as determinants of virulence for A/H5N1 strains. In addition, Lys627 mutation in PB2 protein, polybasic aminoacid mutations in the cleavage region of hemagglutinin (HA) polyprotein, and glycosylation and sialylation mutations in HA and neuraminidase (NA) proteins were found to enhance the immune-mediated patology of highly virulent A/H5N1 strains. In this review article, the immunopathogenesis of influenza infection and the mechanisms of cytokine storm caused by influenza A/H5N1 viruses have been discussed under the light of recent literature.
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PMID:[Cytokine storm in avian influenza]. 1869 37

Preterm and young neonates have an increased predisposition to respiratory distress syndrome (RDS) associated with an immature development of lung surfactant. Glucocorticoids (GCs) are the major immunomodulatory agents used to increase lung development and reduce the mortality and morbidity of preterm infants with RDS. However, their safety remains uncertain, and the precise mechanisms by which they improve lung function are unclear. In previous studies, we found that vascular endothelial growth factor (VEGF) enhances the innate immune response by respiratory epithelial cells, causes a monocytic infiltration into the lung, and reduces the severity of infection by respiratory syncytial virus (RSV), a respiratory pathogen known to affect preterm infants at a high prevalence. The purpose of this study is to measure the effects of VEGF administration on local immune responses in neonatal lambs, as the ovine lung is well suited for comparison to the human lung, due to similarities in alveolar development, immune responses, and RSV susceptibility. We hypothesized that VEGF induces the expression of genes necessary for host immune responses. We analyzed global gene expression profiles in the lungs of neonate lambs treated with VEGF by real-time qPCR. We report that VEGF induced the expression of chemokines (IL-8, RANTES, MCP-1), cytokines (IFN-gamma, IL-6, TNF-alpha, GMCSF), Toll-like receptor (TLR)-4, complement family members (C3, CFB, CFH) and collectins (SP-A, SP-D). These results suggest that VEGF can regulate local immune gene expression in vivo and should be further explored as a potential exogenous therapy for various lung diseases.
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PMID:Gene profiling studies in the neonatal ovine lung show enhancing effects of VEGF on the immune response. 1918 46

Idiopathic pulmonary fibrosis (IPF) is a high risk factor for acute exacerbation of interstitial pneumonia (IP) after pulmonary resection. Other risk factors for inducing IP exacerbation are thought to be intraoperative inhalation of high concentration of oxygen, high pressure mechanical ventilation, major thoracic surgery, massive blood transfusion and preoperative chemotherapy and irradiation. The prophylactic strategy for this phenomenon has not been established, although mechanical ventilation by low pressure and low oxygen concentration, minimum invasive surgery and prophylactic administration of steroid, ulinastatin and sivelestat sodium hydride are performed. Acute exacerbation of IP is the same concept with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). This pulmonary injury is closely associated with reactive oxygen species (ROS). In particular, high concentration of oxygen induces excessive production of ROS. ROS stimulates alveolar macrophages and neutrophils to release inflammatory cytokines, such as TNF-alpha, IL-8, IFN-gamma, IL-6 and IL-1beta. These cytokines injure pulmonary endothelium and alveolus, and atelectasis, pulmonary hemorrhage, lung edema, hyalinization and alveolar thickness occur, and this is a manifestation of ALL Therefore, although there is no evidence, high pressure ventilation and inhalation of high oxygen concentration during anesthesia should be avoided.
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PMID:[The influence of intraoperative oxygen inhalation on patients with idiopathic pulmonary fibrosis]. 2148


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