Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human metapneumovirus (hMPV) is associated with respiratory tract infections among children and adults. Because hMPV induces significant morbidity and mortality in the elderly, a model of hMPV infection in aged BALB/c mice was established. Young (8 weeks old) and aged (18 months old) mice were intranasally inoculated with hMPV. The infected mice showed respiratory dysfunction, as measured by plethysmography, a marked loss in weight (up to 24%), and severe histopathological abnormalities including bronchiolitis obliterans organizing pneumonia. However, clinical severity was far higher in the aged mice, and none of the young infected mice died. Although virus replication in the lung was greater in the older mice, clearance of virus was not delayed compared to young mice. Production of virus-specific antibody as well as neutralizing antibody was lower. Gamma interferon and monocyte chemotactic protein-1 levels in bronchoalveolar lavage fluid were significantly lower in older mice, whereas interleukin-6 and interleukin-4 levels were significantly higher. We observed by flow cytometry a significant increase in the CD4(+) T lymphocytes (P<0.05) of the aged mice and no difference in CD8(+) T-cell recruitment to the respiratory tract between the two groups. The present study investigated the effects of aging on the immunopathogenesis of hMPV infection and suggests that CD4(+) T lymphocytes, the cytokine response, or a defect in humoral response may be associated with the increased disease severity observed in the aged mice.
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PMID:Age-associated aggravation of clinical disease after primary metapneumovirus infection of BALB/c mice. 1914 6

The acute-phase response is characterized by increased circulating levels of acute-phase proteins (APPs) generated by the liver. During bacterial pneumonia, APPs correlate with the severity of disease, serve as biomarkers, and are functionally significant. The kinetics and regulatory mechanisms of APP induction in the liver during lung infection have yet to be defined. Here we show that APP mRNA transcription is induced in the livers of mice whose lungs are infected with either Escherichia coli or Streptococcus pneumoniae, and that in both cases this induction occurs in tandem with activation in the liver of the transcription factors signal transducer and activator of transcription 3 (STAT3) and NF-kappaB RelA. Interleukin-6 (IL-6) deficiency inhibited the activation of STAT3 and the induction of select APPs in the livers of pneumonic mice. Furthermore, liver RelA activation and APP induction were reduced for mice lacking all signaling receptors for tumor necrosis factor alpha and IL-1. In a murine hepatocyte cell line, knockdown of either STAT3 or RelA by small interfering RNA inhibited cytokine induction of the APP serum amyloid A-1, demonstrating that both transcription factors were independently essential for the expression of this gene. These data suggest that during pneumonia caused by gram-negative or gram-positive bacteria, the expression of APPs in the liver depends on STAT3 activation by IL-6 and on RelA activation by early-response cytokines. These signaling axes may be critical for integrating systemic responses to local infection, balancing antibacterial host defenses and inflammatory injury during acute bacterial pneumonia.
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PMID:Mechanisms of the hepatic acute-phase response during bacterial pneumonia. 1928 7

The accuracy of using body temperature, serum amyloid A (SAA), C-reactive protein (CRP) and interleukin-6 (IL-6) in the work-up for early or late step-down therapy after an initial course of intravenous cefuroxime was investigated. Eighty-one hospitalized patients with an initial course of cefuroxime were retrospectively classified with one of the following diagnoses: bacterial infection without known focus, pneumonia, bronchitis, pyelonephritis, skin and soft-tissue infections or fever of other origin. The majority of the patients had sepsis (91% or 74/81) of whom 6 patients had severe sepsis. The inter-individual variability of body temperature, SAA, CRP and IL-6 was considerable. The time course of SAA and CRP during the first 24 h in patients with sepsis with a short duration of illness but without septic shock showed increasing levels during the initial course of intravenous therapy. In contrast, body temperature and IL-6 decreased, regardless of illness duration. Beyond 24 h, all 4 biomarkers declined, again regardless of the duration of illness. After the initial course of cefuroxime, biomarkers were non-distinguishing in terms of guidance in the judgement of early or late step-down therapy. Further studies are proposed for biomarker guidance antibiotic therapy in sepsis patients without septic shock.
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PMID:The time course of body temperature, serum amyloid A protein, C-reactive protein and interleukin-6 in patients with bacterial infection during the initial 3 days of antibiotic therapy. 1962 62

Eosinophils are recruited to the lung in response to infection with pneumovirus pathogens and have been associated with both the pathophysiologic sequelae of infection and, more recently, with accelerated virus clearance. Here, we demonstrate that the pneumovirus pathogens, respiratory syncytial virus (RSV) and pneumonia virus of mice (PVM), can infect human and mouse eosinophils, respectively, and that virus infection of eosinophils elicits the release of disease-related proinflammatory mediators from eosinophils. RSV replication in human eosinophils results in the release of infectious virions and in the release of the proinflammatory mediator, interleukin-6 (IL-6). PVM replication in cultured bone marrow eosinophils (bmEos) likewise results in release of infectious virions and the proinflammatory mediators IL-6, IP-10, CCL2, and CCL3. In contrast to the findings reported in lung tissue of RSV-challenged mice, PVM replication is accelerated in MyD88 gene-deleted bmEos, whereas release of cytokines is diminished. Interestingly, exogenous IL-6 suppresses virus replication in MyD88 gene-deleted bmEos, suggesting a role for a MyD88-dependent cytokine-mediated feedback circuit in modulating this response. Taken together, our findings suggest that eosinophils are targets of virus infection and may have varied and complex contributions to the pathogenesis and resolution of pneumovirus disease.
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PMID:Pneumoviruses infect eosinophils and elicit MyD88-dependent release of chemoattractant cytokines and interleukin-6. 1965 2

Eleven papers on trauma published in Critical Care during 2008 addressed traumatic brain injury (TBI), burns, diagnostic concerns and immunosuppression. In regard to TBI, preliminary results indicate the utility of either magnetic resonance imaging (MRI) or ultrasound in measuring optic nerve sheath diameter to identify elevated intracranial pressure (ICP) as well as the potential benefit of thiopental for refractory ICP. Another investigation demonstrated that early extubation of TBI patients whose Glasgow Coma Scale score was 8 or less did not result in additional incidence of nosocomial pneumonia. Another study indicated that strict glucose control resulted in worse outcomes during the first week after TBI, but improved outcomes after the second week. Another paper showed the prolonged neuroprotective advantages of progesterone administration in TBI patients. There was also guidance on improved classifications of renal complications in burn patients. Another study found that patients with inhalation injuries and increased interleukin-6 (IL-6) and IL-10 and decreased IL-7 had increased mortality rates. One literature review described the disadvantages of prolonged immobilization or additional use of MRI for ruling out cervical spine injuries in obtunded TBI patients already cleared by computerized tomography scans. Other investigators found that higher N-terminal pro B-type natriuretic peptide (NT-proBNP) levels may be useful markers for post-traumatic cardiac impairment. Finally, an experimental model showed that both splenic apoptosis and lymphocytopenia may occur shortly after severe hemorrhage, thus increasing the threat of immunosuppression in those with severe blood loss.
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PMID:Year in review 2008: Critical Care--trauma. 1986 66

We characterized the cellular immune response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in 12- to 14-month-old BALB/c mice, a model that mimics features of the human disease. Following intranasal administration, the virus replicated in the lungs, with peak titers on day 2 postinfection. Enhanced production of cytokines (tumor necrosis factor alpha [TNF-alpha] and interleukin-6 [IL-6]) and chemokines (CXCL10, CCL2, CCL3, and CCL5) correlated with migration of NK cells, macrophages, and plasmacytoid dendritic cells (pDC) into the lungs. By day 7, histopathologic evidence of pneumonitis was seen in the lungs when viral clearance occurred. At this time, a second wave of enhanced production of cytokines (TNF-alpha, IL-6, gamma interferon [IFN-gamma], IL-2, and IL-5), chemokines (CXCL9, CXCL10, CCL2, CCL3, and CCL5), and receptors (CXCR3, CCR2, and CCR5), was detected in the lungs, associated with an influx of T lymphocytes. Depletion of CD8(+) T cells at the time of infection did not affect viral replication or clearance. However, depletion of CD4(+) T cells resulted in an enhanced immune-mediated interstitial pneumonitis and delayed clearance of SARS-CoV from the lungs, which was associated with reduced neutralizing antibody and cytokine production and reduced pulmonary recruitment of lymphocytes. Innate defense mechanisms are able to control SARS-CoV infection in the absence of CD4(+) and CD8(+) T cells and antibodies. Our findings provide new insights into the pathogenesis of SARS, demonstrating the important role of CD4(+) but not CD8(+) T cells in primary SARS-CoV infection in this model.
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PMID:Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS-CoV infection. 1990 20

H9N2 avian influenza viruses have repeatedly caused infections in swine and humans in some countries. The purpose of the present study was to evaluate the pulmonary pathology caused by H9N2 viral infection in mice. Six- to eight-week-old BALB/c mice were infected intranasally with 1 x 10(4) MID(50) of A/Chicken/Hebei/4/2008(H9N2) virus. Clinical signs, pathological changes and viral replication in lungs, arterial blood gas, and cytokines in bronchoalveolar lavage fluid (BALF) were observed at different time points after infection. A control group was infected intranasally with noninfectious allantoic fluid. H9N2-infected mice exhibited severe respiratory syndrome, with a mortality rate of 60%. Gross observations showed that infected lungs were highly edematous. Major histopathological changes in infected lungs included diffuse pneumonia and alveolar damage, with neutrophil-dominant inflammatory cellular infiltration, interstitial and alveolar edema, hemorrhage, and severe bronchiolitis/peribronchiolitis. In addition, H9N2 viral infection resulted in severe progressive hypoxemia, lymphopenia, and a significant increase in neutrophils, tumor necrosis factor-alpha and interleukin-6 in BALF. The features described above satisfy the criteria for acute respiratory distress syndrome (ARDS). Our data show that H9N2 viral infection resulted in ARDS in mice, and this may facilitate studies of the pathogenesis of future potential H9N2 disease in humans.
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PMID:Acute respiratory distress syndrome induced by H9N2 virus in mice. 1994 15

In large series of nonresponding community-acquired pneumonia (CAP) patients, chronic obstructive pulmonary disease (COPD) was observed to be a protective factor for nonresponse to initial antibiotics. This intriguing fact may be linked to changes in the phenotype of inflammatory cells and, in particular, to the induction of classical-M1 or alternative-M2 activation of macrophages, which result in different inflammatory profiles. We evaluated the effect of sputum obtained from patients with acute exacerbation of COPD (AECOPD), CAP and COPD+CAP on the phenotypic changes in macrophages. Human THP1 cells differentiated to macrophages were incubated with sputum from patients with AECOPD, CAP or COPD+CAP, and expression of tumour necrosis factor-alpha, interleukin-6, mannose receptor and arginase was measured to evaluate the phenotype acquired by macrophages. We found that sputum from CAP patients induced the M1 phenotype and that from AECOPD patients induced an M2-like phenotype. Sputum from CAP+COPD patients did not present a clear M1 or M2 phenotype. These results indicate that the microenvironment in the lung modulates the activation of macrophages, resulting in different phenotypes in AECOPD, CAP and COPD+CAP patients. This different type of activation induces different inflammatory responses and may be involved in the different outcome observed when COPD and CAP present simultaneously.
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PMID:Macrophage activation in exacerbated COPD with and without community-acquired pneumonia. 2003 16

While sepsis is a leading cause of acute kidney injury in critically ill patients, the relationship between immune response and acute kidney injury in less severely ill patients with infection is not known. Here we studied the epidemiology, 1-year mortality, and immune response associated with acute kidney injury in 1836 hospitalized patients with community-acquired severe and non-severe pneumonia. Acute kidney injury developed in 631 patients of whom 329 had severe and 302 had non-severe sepsis. Depending on the subgroup classification, 16-25% of the patients with non-severe pneumonia also developed acute kidney injury. In general, patients with acute kidney injury were older, had more comorbidity, and had higher biomarker concentrations (interleukin-6, tumor necrosis factor, D-dimer) even among patients without severe sepsis. The risk of death associated with acute kidney injury varied when assessed by Gray's survival model and after adjusting for differences in age, gender, ethnicity, and comorbidity. This risk was significantly higher immediately after hospitalization but gradually fell over time in the overall cohort and in those with non-severe pneumonia. A significantly higher risk of death (hazard ratio 1.29) was also present in those never admitted to an intensive care unit. Hence acute kidney injury is common even among patients with non-severe pneumonia and is associated with higher immune response and an increased risk of death.
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PMID:Acute kidney injury in non-severe pneumonia is associated with an increased immune response and lower survival. 3231 98

Secondary bacterial infections that follow infection with influenza virus result in considerable morbidity and mortality in young children, the elderly, and immunocompromised individuals and may also significantly increase mortality in normal healthy adults during influenza pandemics. We herein describe a mouse model for investigating the interaction between influenza virus and the bacterium Haemophilus influenzae. Sequential infection with sublethal doses of influenza and H. influenzae resulted in synergy between the two pathogens and caused mortality in immunocompetent adult wild-type mice. Lethality was dependent on the interval between administration of the bacteria and virus, and bacterial growth was prolonged in the lungs of dual-infected mice, although influenza virus titers were unaffected. Dual infection induced severe damage to the airway epithelium and confluent pneumonia, similar to that observed in victims of the 1918 global influenza pandemic. Increased bronchial epithelial cell death was observed as early as 1 day after bacterial inoculation in the dual-infected mice. Studies using knockout mice indicated that lethality occurs via a mechanism that is not dependent on Fas, CCR2, CXCR3, interleukin-6, tumor necrosis factor, or Toll-like receptor-4 and does not require T or B cells. This model suggests that infection with virulent strains of influenza may predispose even immunocompetent individuals to severe illness on secondary infection with H. influenzae by a mechanism that involves innate immunity, but does not require tumor necrosis factor, interleukin-6, or signaling via Toll-like receptor-4.
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PMID:A mouse model of lethal synergism between influenza virus and Haemophilus influenzae. 2001 94


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