UMLS:C0032285 - FACTA Search

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Query: UMLS:C0032285 (pneumonia)
54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease with significant morbidity and mortality. An epidemic in 2003 affected 8,098 patients in 29 countries with 774 deaths. The aetiological agent is a new coronavirus spread by droplet transmission. Clinical and general laboratory manifestations included fever, chills, rigor, myalgia, malaise, diarrhoea, cough, dyspnoea, pneumonia, lymphopenia, neutrophilia, thrombocytopenia, and elevated serum lactate dehydrogenase (LD), alanine aminotransferase (ALT) and creatine kinase (CK) activities. Treatment has been empirical; initial potent antibiotic cover, followed by simultaneous ribavirin and corticosteroids, with or without pulse high-dose methylprednisolone, have been used. The postulated disease progression comprises (1) active viral infection, (2) hyperactive immune response, and (3) recovery or pulmonary destruction and death. We investigated serum LD isoenzymes and blood lymphocyte subsets of SARS patients, and found LD1 activity as the best biochemical prognostic indicator for death, while CD3+, CD4+, CD8+ and natural killer cell counts were promising predictors for intensive care unit (ICU) admission. Plasma cytokine and chemokine profiles showed markedly elevated Th1 cytokine interferon (IFN)-gamma, inflammatory cytokines interleukin (IL)-1beta, IL-6 and IL-12, neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-gamma-inducible protein-10 (IP-10) for at least two weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumor necrosis factor (TNF)-alpha and anti-inflammatory cytokine IL-10. Corticosteroid reduced IL-8, MCP-1 and IP-10 concentrations from 5-8 days after treatment. Measurement of biochemical markers of bone metabolism demonstrated significant but transient increase in bone resorption from Day 28-44 after onset of fever, when pulse steroid was most frequently given. With tapering down of steroid therapy, there was a decrease in bone resorption marker together with an increase in bone formation markers round Day 50, suggesting that some of the bone loss might be reversed. Our research studies on the chemical pathology and clinical immunology of SARS should have implications for the pathophysiology and therapy of this potentially lethal infection.
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PMID:Severe acute respiratory syndrome: clinical and laboratory manifestations. 1845 12

Legionella pneumophila causes severe pneumonia. Acetylation of histones is thought to be an important regulator of gene transcription, but its impact on L. pneumophila-induced expression of proinflammatory cytokines is unknown. L. pneumophila strain 130b induced the expression of the important chemoattractant IL-8 and genome-wide histone modifications in human lung epithelial A549 cells. We analyzed the IL-8-promoter and found that histone H4 was acetylated and H3 was phosphorylated at Ser(10) and acetylated at Lys(14), followed by transcription factor NF-kappaB. Recruitment of RNA polymerase II to the IL-8 promoter corresponded with increases in gene transcription. Histone modification and IL-8 release were dependent on p38 kinase and NF-kappaB pathways. Legionella-induced IL-8 expression was decreased by histone acetylase (HAT) inhibitor anacardic acid and enhanced by histone deacetylase (HDAC) inhibitor trichostatin A. After Legionella infection, HATs p300 and CREB-binding protein were time-dependently recruited to the IL-8 promoter, whereas HDAC1 and HDAC5 first decreased and later reappeared at the promoter. Legionella specifically induced expression of HDAC5 but not of other HDACs in lung epithelial cells, but knockdown of HDAC1 or 5 did not alter IL-8 release. Furthermore, Legionella-induced cytokine release, promoter-specific histone modifications, and RNA polymerase II recruitment were reduced in infection with flagellin-deletion mutants. Legionella-induced histone modification as well as HAT-/HDAC-dependent IL-8 release could also be shown in primary lung epithelial cells. In summary, histone acetylation seems to be important for the regulation of proinflammatory gene expression in L. pneumophila infected lung epithelial cells. These pathways may contribute to the host response in Legionnaires' disease.
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PMID:Histone acetylation and flagellin are essential for Legionella pneumophila-induced cytokine expression. 1860 45

Rhodococcus equi is an intracellular pathogen of macrophages that causes rhodococcal pneumonia in foals and immunocompromised people. Evidence exists that neutrophils play a vital role in resistance to infection with R. equi; however, the means by which neutrophils exert their effects have not been clearly defined. In addition to directly killing bacteria, neutrophils also may exert a protective effect by linking innate and adaptive immune responses. In the present study we evaluated the cytokine expression profiles of adult equine neutrophils in response to stimulation with isogenic strains of virulent and avirulent R. equi in vitro. After 2 and 4h incubation with virulent or avirulent R. equi, adult equine neutrophils expressed significantly (P<0.05) greater tumor necrosis factor alpha (TNFalpha), interleukin (IL)-12p40, IL-6, IL-8 and IL-23p19 mRNA, but not interferon gamma (IFNgamma) or IL-12p35 mRNA than unstimulated neutrophils. Furthermore, virulent R. equi induced significantly greater IL-23p19 mRNA than avirulent R. equi. These results demonstrate that R. equi-stimulated neutrophils are a source of many proinflammatory cytokines. Furthermore, these results suggest that IL-23 may be preferentially expressed over IL-12 in response to exposure with R. equi, and that this response may be more strongly induced by virulent R. equi than avirulent R. equi. Collectively, the data presented herein suggest a non-phagocytic role for neutrophils that may influence the type of adaptive immune response to R. equi.
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PMID:Cytokine expression by neutrophils of adult horses stimulated with virulent and avirulent Rhodococcus equi in vitro. 1901 57

Although evidence exists that neutrophils play a vital role in resistance to infection with Rhodococcus equi, the means by which neutrophils exert their effects have not been clearly defined. In the present study we evaluated differences in cytokine expression by unstimulated and R. equi-stimulated neutrophils obtained from newborn foals and subsequently at 2-, 4-, and 8-weeks of age. Stimulation with virulent R. equi induced significantly (P<0.05) greater expression of IFNgamma, TNFalpha, IL-6, IL-8, IL-12p40, IL-12p35, and IL-23p19 mRNA relative to expression by unstimulated neutrophils, and there were significant effects of age on expression of IL-6, IL-8, IL-12p40 and IL-23p19. Neutrophil expression of IL-6 and IL-8 in newborn foals was significantly greater than expression at 2-, 4-, and 8-weeks of age. Expression of IL-12p40 by R. equi-stimulated neutrophils from newborn and 2-week-old foals did not differ from that of unstimulated neutrophils; however, expression of IL-12p40 by neutrophils from 4- and 8-week-old foals was significantly greater when stimulated by R. equi than without stimulation. These results demonstrate that foal neutrophils increase mRNA expression of many pro-inflammatory cytokines, including IFNgamma, in response to in vitro stimulation with R. equi, and that the magnitude of this expression with respect to IL-6, IL-8, IL-12p40 and IL-23p19 is influenced by age. The clinical importance of the age-related difference in R. equi-induced expression of IL-12p40 to susceptibility to R. equi pneumonia remains to be determined.
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PMID:Age-related changes in cytokine expression by neutrophils of foals stimulated with virulent Rhodococcus equi in vitro. 1902 56

Phagocytes of the reticuloendothelial system are important in clearing systemic infection; however, the role of the reticuloendothelial system in the response to localized infection is not well-documented. The major goals of this study were to investigate the roles of phagocytes in the reticuloendothelial system in terms of bacterial clearance and inflammatory modulation in sepsis caused by Pseudomonas pneumonia. Macrophages in liver and spleen were depleted by administering liposome encapsulated dichloromethylene diphosphonate (clodronate) intravenously 36 h before the instillation of Pseudomonas aeruginosa into the lungs of anesthetized rabbits. Blood samples were analyzed for bacteria and cytokine concentrations. Lung injury was assessed by the bidirectional flux of albumin and by wet-to-dry weight ratios. Blood pressure and cardiac outputs decreased more rapidly and bacteremia occurred earlier in the clodronate-treated rabbits compared with the nondepleted rabbits. Plasma TNF-alpha (1.08 +/- 0.54 vs. 0.08 +/- 0.02 ng/ml) and IL-8 (6.8 +/- 1.5 vs. 0.0 +/- 0.0 ng/ml) were higher in the depleted rabbits. The concentration of IL-10 in liver of the macrophage-depleted rabbits was significantly lower than in normal rabbits at 5 h. Treatment of macrophage-depleted rabbits with intravenous IL-10 reduced plasma proinflammatory cytokine concentrations and reduced the decline in blood pressure and cardiac output. These results show that macrophages in the reticuloendothelial system have critical roles in controlling systemic bacteremia and reducing systemic inflammation, thereby limiting the systemic effects of a severe pulmonary bacterial infection.
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PMID:Depletion of phagocytes in the reticuloendothelial system causes increased inflammation and mortality in rabbits with Pseudomonas aeruginosa pneumonia. 1902 78

A 37-year-old woman presenting with high fever, dry cough and progressive dyspnea was admitted to our hospital. She took 100 mg of minocycline hydrochloride orally because of a common cold one day prior to her admission. A chest CT scan showed diffuse ground-glass opacities with interlobular septal thickening and thickening of bronchovascular bundles. An analysis of bronchoalveolar lavage fluid showed an increase in both the total cell counts and the number of eosinophils. The result of a lymphocyte stimulation test performed on peripheral blood lymphocytes was positive for minocycline. This patient had a history of pneumonia with similar clinical and radiographic findings, which had developed while receiving minocycline. As a result, we made a diagnosis of minocycline-induced acute eosinophilic pneumonia. Her symptoms and radiographic findings improved within a few days after admission. Corticosteroid therapy was effective. A marked increase of peripheral blood neutrophils were noted on admission. The serum levels of IL-8 and G-CSF increased at the early phase of the disease, but thereafter decreased in association with neutrophils, thus suggesting the contribution of these cytokines to the early phase neutrophilia in this case.
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PMID:[Case of minocycline-induced acute eosinophilic pneumonia accompanied by marked neutrophilia in the peripheral blood]. 1904 33

Methotrexate (MTX) has been widely used for the treatment of inflammatory diseases and rheumatoid arthritis (RA), as well as a variety of tumors. However, MTX-induced toxicity is a serious and unpredictable side effect of this therapy and an important clinical problem. We used microarray analysis to examine MTX-induced gene expression in a human lung epithelial cell line (BEAS-2B) and identified 10 differentially expressed genes related to the p38 mitogen-activated protein kinase (MAPK) pathway, including IL-1beta, MKK6, and MAPKAPK2. Differential gene expression was confirmed via real-time RT-PCR. To determine the functional significance of MTX-induced p38 MAPK activation, we used a p38 MAPK inhibitor (SB203580) to block the p38 MAPK cascade. We also used protein array technology to investigate the modulated expression of pro- and anti-inflammatory cytokines in BEAS-2B cells. MTX activated IL-1beta expression and induced the phosphorylation of various proteins in the p38 MAPK cascade, including TAK1, MKK3/MKK6, p38 MAPK, MAPKAPK2, and HSP27. Finally, HSP27 activation may increase IL-8 secretion, resulting in a pulmonary inflammatory response such as pneumonitis. Although IL-1beta and IL-8 expression increased, the expression of IL-4, IL-6, IL-12, TNF-alpha, MIP-1alpha, and MIP-1beta decreased in a dose-dependent manner. These results suggest that the modulation of cytokine expression may play an important role in MTX-induced pulmonary toxicity.
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PMID:Inflammation in methotrexate-induced pulmonary toxicity occurs via the p38 MAPK pathway. 1910 Mar 7

Alveolar type II epithelial cells (ATIIs) are one of the primary targets for influenza A pneumonia. The lack of a culture system for maintaining differentiated ATIIs hinders our understanding of pulmonary innate immunity during viral infection. We studied influenza A virus (IAV)-induced innate immune responses in differentiated primary human ATIIs and alveolar macrophages (AMs). Our results indicate that ATIIs, but not AMs, support productive IAV infection. Viral infection elicited strong inflammatory chemokine and cytokine responses in ATIIs, including secretion of IL-8, IL-6, MCP-1, RANTES, and MIP-1beta, but not TNF-alpha, whereas AMs secreted TNF-alpha as well as other cytokines in response to infection. Wild-type virus A/PR/8/34 induced a greater cytokine response than reassortant PR/8 virus, A/Phil/82, despite similar levels of replication. IAV infection increased mRNA expression of IFN genes IFN-beta, IL-29 (IFN-lambda1), and IL-28A (IFN-lambda2). The major IFN protein secreted by type II cells was IL-29 and ATIIs appear to be a major resource for production of IL-29. Administration of IL-29 and IFN-beta before infection significantly reduced the release of infectious viral particles and CXC and CC chemokines. IL-29 treatment of type II cells induced mRNA expression of antiviral genes MX1, OAS, and ISG56 but not IFN-beta. IL-29 induced a dose-dependent decrease of viral nucleoprotein and an increase of antiviral genes but not IFN-beta. These results suggest that IL-29 exerts IFN-beta-independent protection in type II cells through direct activation of antiviral genes during IAV infection.
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PMID:Differentiated human alveolar type II cells secrete antiviral IL-29 (IFN-lambda 1) in response to influenza A infection. 1915 75

Acute respiratory failure in neonates (e.g. ARDS, meconium aspiration pneumonitis, pneumonia) is characterized by an excessive inflammatory response, governing the migration of polymorpho-nuclear leukocytes (PMNLs) into lung tissue and causing consecutive impairment of gas exchange and lung function. Critical to this inflammatory response is the activation of nuclear factor-kappaB (NF-kappaB) that is required for transcription of the genes for many pro-inflammatory mediators. We asked whether the inhibition of NF-kappaB activity using either a selective inhibitor (IKK-NBD peptide) or dexamethasone would be more effective in decreasing NF-kappaB activity and chemokine expression in pulmonary cells. Changes in lung function were repeatedly assessed for 24h following induction of acute respiratory failure and therapeutic intervention. We conducted a randomized, controlled, prospective animal study with mechanically ventilated newborn piglets which underwent repeated airway lavage (20+/-2 [SEM]) to remove surfactant and to induce lung inflammation. Admixed to 100 mg kg(-1) surfactant, piglets then received either IKK-NBD peptide (S+IKK), a selective inhibitor of NF-kappaB activation, its control peptide without intrinsic activity, dexamethasone (S+Dexa), its solvent aqua, or an air bolus only (all groups n=8). After 24h of mechanical ventilation, the following differences were measured: PaO(2)/FiO(2) (S+IKK 230+/-9 mm Hg vs. S+Dexa 188+/-14, p<0.05); ventilation efficiency index (0.18+/-0.01 [3800/(PIP-PEEP)(*)f(*)PaCO(2)] vs. 0.14+/-0.01, p<0.05); extravascular lung water (24+/-1 ml kg(-1) vs. 29+/-2, p<0.05); PMNL in BAL fluid (112+/-21 cells microl(-1) vs. 208+/-34, p<0.05), IL-8 (351+/-117 pg ml(-1) vs. 491+/-144, p=ns) and leukotriene B(4) (23+/-7 pg ml(-1) vs. 71+/-11, p<0.01) in BAL fluid. NF-kappaB activity in the nucleus of pulmonary cells differed by 32+/-5% vs. 55+/-3, p<0.001. Differences between these two intervention groups were more pronounced in the second half of the observation period (hours 12-24). At 24h of mechanical ventilation, inhibition of NF-kappaB activity by IKK-NBD peptide admixed to surfactant as a carrier caused improved gas exchange, lung function and reduced pulmonary inflammation, as evidenced by reduction in PMNL migration into lung tissue due to reduced nuclear NF-kappaB activity. We conclude that IKK-NBD admixture to surfactant in acute neonatal respiratory failure is superior to dexamethasone administration within the first 24h.
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PMID:Selective NF-kappaB inhibition, but not dexamethasone, decreases acute lung injury in a newborn piglet airway inflammation model. 1925 76

Respiratory infection of cattle with bovine herpesvirus type 1 (BHV-1) predisposes cattle to secondary pneumonia with Mannheimia haemolytica as part of the bovine respiratory disease complex (BRD). One cell type that has received limited investigation for its role in the inflammation that accompanies BRD is the respiratory epithelial cell. In the present study we investigated mechanisms by which BHV-1 infection of respiratory epithelial cells contributes to the recruitment and activation of bovine polymorphonuclear neutrophils (PMNs) in vitro. Primary cultures of bovine bronchial epithelial (BBE) cells were infected with BHV-1 and assessed for cytokine expression by real-time PCR. We found that BHV-1 infection elicits a rapid IL-1, IL-8 and TNF-alpha mRNA response by BBE cells. Bovine PMNs exhibited greater adherence to BHV-1 infected BBE cells than uninfected cells. The increased adherence was significantly reduced by the addition of an anti-IL-1beta antibody or human soluble TNF-alpha receptor (sTNF-alphaR). Pre-incubation of bovine PMNs with conditioned media from BHV-1 infected BBE cells increased PMN migration, which was inhibited by addition of an anti-IL-1beta antibody, sTNF-alphaR, or an IL-8 peptide inhibitor. Conditioned media from BHV-1 infected BBE cells activated bovine PMNs in vitro as demonstrated by PMN shape change, production of reactive oxygen species and degranulation. PMNs also exhibited increased LFA-1 expression and susceptibility to M. haemolytica LKT following incubation with BHV-1 infected BBE cell conditioned media. Our results suggest that BHV-1 infection of BBE cells triggers cytokine expression that contributes to the recruitment and activation of neutrophils, and amplifies the detrimental effects of M. haemolytica LKT.
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PMID:Bovine herpesvirus type 1 infection of bovine bronchial epithelial cells increases neutrophil adhesion and activation. 1940 83

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