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

Epidemiological studies have indicated that exposure to elevated levels of particulate matter exacerbates several pulmonary diseases, including asthma, bronchitis, and viral infections. Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in infants and may lead to the development of asthma in childhood. To determine whether particle exposure modulates the immune response to RSV, eight-week-old female BALB/c mice received an intratracheal (i.t.) instillation of either 40 micro g ultrafine carbon black (CB) particles or vehicle. The following day, mice were i.t. instilled with either 106 pfu RSV or uninfected media. End points were examined 1, 2, 4, 7, and 10 days during RSV infection. Compared with RSV alone, tumor necrosis factor-alpha (TNF-alpha) protein was reduced in the bronchoalveolar lavage fluid (BALF) on days 1 and 2 of infection; there was also a reduction in BALF lymphocyte numbers on day 4, which correlated with reductions in both IFN-gamma-inducible protein (IP-10), lymphotactin, and IFN-gamma mRNAs in the lungs of RSV + CB mice. Multiprobe ribonuclease protection assays of RSV + CB lung tissue showed no changes in the RSV-associated chemokines regulated upon activation, normal T cell expressed and secreted (RANTES), eotaxin, monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP)-1 alpha or MIP-1 beta. Viral titers in RSV + CB mice were lower than RSV on days 2-4 of infection. By day 7 of infection, however, neutrophil numbers, proinflammatory cytokine mRNA expression, and protein levels of TNF-alpha and the Th2 cytokine interleukin (IL)-13 were increased in the lungs of RSV + CB mice, indicating an exacerbation of infection. These data indicate that preexposure to ultrafine particles induces an inflammatory milieu promoting allergic immune responses rather than IFNgamma production necessary for microbial defense.
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PMID:Effect of preexposure to ultrafine carbon black on respiratory syncytial virus infection in mice. 1266 Mar 65

We have studied the changes in the serum level of the following cytokines during the course of treatment of nosocomial pneumonia (NP): pro-inflammatory--IL-1alpha and IL-6, chemoattractive--IL-8, anti-inflammatory--IL-4 and IL-10, and differentiating-activating--IFN-gamma and TNF-alpha. It has been found that at the time of admission of the patients the clinical severity of their condition was correlated with increased levels of all circulating cytokines except for IFN-gamma, the level of which was low. An adequate ethiotropic therapy helped to clear the clinical symptoms of infection and intoxication in 1-2 weeks. The level of circulating pro- and anti-inflammatory cytokines, IL-8, and TNF-alpha was decreasing, however, the level of IFN-gamma did not change significantly during 15 days. The ratio IFN-gamma/IL-10 did not change much but was slightly low during the treatment of the severe form of NP. Radical positive changes in the cytokine dynamics were achieved after the addition of leukinferon to the ethiotropic therapy.
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PMID:Dynamics of cytokines and role of immunocorrection in nosocomial pneumonia. 1268 58

The study was designed to determine whether alveolar macrophages (AM) in acute pulmonary sarcoidosis release in vitro the anti-inflammatory cytokine interleukin (IL)-10. To learn more about the coherence between IL-10 and proinflammatory cytokines in active sarcoidosis, the release of interferon (IFN)-gamma, macrophage inhibitory protein (MIP)-1alpha, and granulocyte-macrophage colony-stimulating factor (GM-CSF) was studied and additionally compared to normal controls and patients with pneumonia and interstitial lung fibrosis. AM were obtained by bronchoalveolar lavage from 13 patients with active sarcoidosis, 8 patients with interstitial lung fibrosis, 10 patients with bacterial pneumonia, and 14 normal controls. The spontaneous and stimulated (tumor necrosis factor [TNF]-alpha, IL-1beta) cytokine release was measured in the supernatant of cultured AM by enzyme-linked immunosorbent assay (ELISA). Unstimulated AM from sarcoidosis patients released more IL-10, IFN-gamma, MIP-1alpha, and GM-CSF than normal controls and patients with pneumonia and interstitial lung disease. Stimulation with TNF-alpha or IL-1beta increased the MIP-1alpha and GM-CSF release from AM of normal controls and patients with pneumonia and interstitial lung disease: however, no further enhancement of MIP-1alpha and GM-CSF production was observed in AM from sarcoidosis patients. Exogenous IL-10 reduced the spontaneous and stimulated MIP-1alpha and GM-CSF release in sarcoidosis to a lesser extent than in controls and patients with fibrosis and pneumonia. The up-regulated IL-10 in active pulmonary sarcoidosis may be a compensatory response to the enhanced expression of proinflammatory cytokines in order to down-regulate the inflammatory process. The results suggest an involvement of the anti-inflammatory cytokine IL-10 in the immunopathogenesis of sarcoidosis.
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PMID:Increased spontaneous interleukin-10 release from alveolar macrophages in active pulmonary sarcoidosis. 1274 45

Patients with large burn injuries are susceptible to opportunistic infections due to impaired functions of multiple effector cells of innate immunity and acquired immunity, including macrophages, dendritic cells (DC), natural killer (NK) cells, and T cells. The ability of a host to produce Th1 cytokines, such as gamma interferon (IFN-gamma) and interleukin-12 (IL-12), upon infectious challenge is also impaired after burn injury. Stimulation of hematopoiesis, to regenerate new immune cells, may be an effective strategy for improving resistance to infections after severe burn trauma. Fms-like tyrosine kinase 3 ligand (Flt3L) is a hematopoietic cytokine that stimulates the expansion and differentiation of NK cells and DC. Using a mouse model, we tested the hypothesis that Flt3L treatments after burn injury stimulate the production of functional effector cells of innate immunity and restore appropriate Th1 cytokine responses to Pseudomonas aeruginosa, a common source of pneumonia and wound infections in burn victims. Flt3L increased splenic cellularity in sham (uninjured) and burned mice and increased the numbers of NK cells (DX5(+)) and DC (CD11c(+)). In response to P. aeruginosa, significant increases in the serum IFN-gamma levels and the numbers of splenic IFN-gamma-producing DC, NK cells, and T cells were observed in Flt3L-treated burned mice compared to the values obtained for untreated burned mice. The splenic levels of IL-12 and IL-15 mRNAs and the IL-12 and IL-15 receptors were also increased. In addition, Flt3L treatment restored the ability of splenic cultures prepared from burned mice to produce IFN-gamma and IL-12 after in vitro challenge with P. aeruginosa. Flt3L may have potential for restoring NK cell and DC functions and improving immunity after burn injury.
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PMID:Stimulation of hematopoiesis by the Fms-like tyrosine kinase 3 ligand restores bacterial induction of Th1 cytokines in thermally injured mice. 1276 Oct 83

Gamma interferon-deficient (IFN-gamma KO) mice developed a wasting syndrome and were found to be co-infected with Helicobacter sp., and a new isolate of mouse hepatitis virus (MHV) designated MHV-G. The disease was characterized by pleuritis, peritonitis, hepatitis, pneumonia, and meningitis. Initial experiments used a cecal homogenate inoculum from the clinical cases that contained H. hepaticus and MHV-G to reproduce the development of peritonitis and pleuritis in IFN-gamma KO mice. In contrast, immunocompetent mice given the same inoculum developed an acute, self-limiting infection and remained clinically normal. This result confirmed the importance of IFN-gamma in preventing chronic infection and limiting viral dissemination. To understand the role of both agents in the development of peritonitis and pleuritis, IFN-gamma KO mice were infected with either agent or were co-infected with H. hepaticus and MHV-G. Infection with MHV-G induced a multisystemic infection similar to that described in the original cases, with multifocal hepatic necrosis, acute necrotizing and inflammatory lesions of the gastrointestinal tract, and acute peritonitis and pleuritis with adhesions on the serosal surfaces of the viscera. However, mice given H. hepaticus alone had minimal pathologic changes even though the organism was consistently detected in the cecum or feces. Although co-infection with H. hepaticus and MHV-G induced lesions similar to those associated with MHV-G alone, the pathogenesis of the MHV infection was modified. Helicobacter hepaticus appeared to reduce the severity of MHV-induced lesions during the acute phase of infection, and exacerbated hepatitis and meningitis at the later time point. We conclude that infection of IFN-gamma KO mice with MHV-G results in multisystemic infection with peritonitis, pleuritis, and adhesions due to the aberrant immune response in these mice. In addition, co-infection of these mice with H. hepaticus results in alterations in the pathogenesis of MHV-G infection.
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PMID:Pathogenesis of mouse hepatitis virus infection in gamma interferon-deficient mice is modulated by co-infection with Helicobacter hepaticus. 1278 55

Major histocompatibility complex (MHC) class II antigen presentation and subsequent CD4+ T-cell activation are critical for acquired immunity to Mycobacterium tuberculosis infection. MHC class II gene expression is primarily controlled by the master transactivator CIITA protein. Without functional CIITA protein, MHC class II expression is lost, impairing immune responses and increasing susceptibility to infection. In this study, we compared protective immune responses of CIITA-deficient mice and wild-type C57BL/6 controls with low dose aerosol M. tuberculosis infection. After aerogenic challenge, CIITA-/- mice failed to limit mycobacterial growth (2.5 and 2.0 log10 > WT lung and spleen CFUs, respectively, at day 58). Lung histopathology involved extensive necrosis, severe pneumonitis and overwhelming inflammation in the gene knockout mice. Mean survival time for CIITA-/- mice was significantly reduced (57 versus >300 days for WT). This extreme sensitivity to tuberculous infection was largely attributed to the absence of CD4+ cells. Flow cytometric studies detected virtually no CD4+ cells in CIITA-/- mouse spleens after infection versus elevated numbers in WT spleens. Failed CD4+ T-cell expansion markedly reduced interferon-gamma (IFN-gamma production in CIITA-/- mice versus WT controls. These results suggest the necessity of a functional CIITA pathway for controlling tuberculous infections and that interventions targeting CIITA expression may be useful antimycobacterial therapeutics.
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PMID:Susceptibility of mice deficient in the MHC class II transactivator to infection with Mycobacterium tuberculosis. 1282 54

Despite the well-recognized role of adenoviruses of species B in the etiology of severe respiratory disease, the lack of an experimental in vivo model system has limited the understanding of the molecular pathogenesis of species B adenovirus-induced pneumonia. Intratracheal instillation of 5 x 10(8) plaque-forming units (pfu) of adenoviruses 3p and 7h resulted in a robust inflammatory response in the lungs of infected mice. A marked infiltration of neutrophils into the lung air spaces was observed at 1 and 2 days postinfection (dpi), with a concomitant increase in the levels of neutrophil chemokines MIP-2 and KC. The overall histological severity scores were significantly higher for Ad3p-infected mice at 2 dpi, but similar between the two viruses at other time points. Remodeling of the airway epithelia and mucous cell metaplasia were noted in the proximal airways of infected mice, indicating marked epithelial differentiation and/or injury. The proinflammatory cytokines interleukin-beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma [see symbol in text]), and interleukin-12 (IL-12) were induced by viral infection. Expression of the early viral immunomodulatory genes E3-15.3K and E3gp19K mRNA was readily detectable in the lungs of infected mice by reverse transcription-polymerase chain reaction (RT-PCR) at 1 and 2 dpi, coinciding with the peak levels of TNF-alpha. While the detection of gp19K mRNA declined thereafter, 15.3K mRNA was detectable up to 6 dpi. Our results indicate that human Ad3 and Ad7 cause marked pulmonary pathology, inducing similar host responses in the respiratory tract, thus validating the use of the mouse model for the study of early virus-host interactions during lung infection by adenoviruses of subspecies B1.
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PMID:Acute inflammatory response and remodeling of airway epithelium after subspecies B1 human adenovirus infection of the mouse lower respiratory tract. 1293 98

Infections are a leading cause of death in stroke patients. In a mouse model of focal cerebral ischemia, we tested the hypothesis that a stroke-induced immunodeficiency increases the susceptibility to bacterial infections. 3 d after ischemia, all animals developed spontaneous septicemia and pneumonia. Stroke induced an extensive apoptotic loss of lymphocytes and a shift from T helper cell (Th)1 to Th2 cytokine production. Adoptive transfer of T and natural killer cells from wild-type mice, but not from interferon (IFN)-gamma-deficient mice, or administration of IFN-gamma at day 1 after stroke greatly decreased the bacterial burden. Importantly, the defective IFN-gamma response and the occurrence of bacterial infections were prevented by blocking the sympathetic nervous system but not the hypothalamo-pituitary-adrenal axis. Furthermore, administration of the beta-adrenoreceptor blocker propranolol drastically reduced mortality after stroke. These data suggest that a catecholamine-mediated defect in early lymphocyte activation is the key factor in the impaired antibacterial immune response after stroke.
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PMID:Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. 3162 20

The cytokine profile associated with either a T helper 1 (Th1) or Th2 response in a porcine respiratory disease model was assessed by measuring IL-12, IL-10 and IFN-gamma using RT-PCR and ELISA, respectively. IL-10, IL-12, and IFN-gamma levels in pulmonary alveolar macrophages and bronchial lavage fluid were increased in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV), Mycoplasma hyopneumoniae, or both pathogens. At 10 days post-infection (DPI), both IL-10 and IL-12 mRNA levels were increased in both groups infected with PRRSV. The IL-12 levels were increased in pigs infected with both pathogens and IFN-gamma protein levels were increased in pigs infected with PRRSV alone and only numerically increased in the dual infection. At 28 DPI, IL-12 mRNA levels and IL-10 protein levels were increased in all infected groups. The mRNA level of IL-12 remained elevated in the group infected with both pathogens at 42 DPI. Production of IFN-gamma did not appear to be closely correlated with elimination of virus from the respiratory tract. However, when the virus existed in the lung, the local IFN-gamma production appeared to increase. Although IL-12 mRNA levels were significantly elevated in the pigs infected with both pathogens, the increased protein levels of IL-12 may compromise the immune system's ability to clear PRRSV from the lung. This could explain the prolonged presence of PRRSV, IFN-gamma production and the increased pneumonia observed in the lungs of dual-infected pigs. The increased levels of cytokines associated with both Th1 and Th2 responses in the respiratory tract of pigs infected with PRRSV and M. hyopneumoniae provides valuable information on the pathogenesis of these diseases.
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PMID:Interleukin-10, interleukin-12, and interferon-gamma levels in the respiratory tract following mycoplasma hyopneumoniae and PRRSV infection in pigs. 1458 50

Host defenses are profoundly compromised in HIV-infected hosts due to progressive depletion of CD4+ T lymphocytes. A hallmark of HIV infection is Pneumocystis carinii (PC) pneumonia. Recently, CD8+ T cells, which are recruited to the lung in large numbers in response to PC infection, have been associated with some level of host defense as well as contributing to lung injury in BALB/c mice. In this study, we show that CD8+ T cells that have a T cytotoxic-1 response to PC in BALB/c mice, as determined by secretion of IFN-gamma, have in vitro killing activity against PC and effect clearance of the organism in adoptive transfer studies. Moreover, non-T cytotoxic-1 CD8+ T cells lacked in vitro effector activity and contributed to lung injury upon adoptive transfer. This dichotomous response in CD8+ T cell response may in part explain the clinical heterogeneity in the severity of PC pneumonia.
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PMID:T cytotoxic-1 CD8+ T cells are effector cells against pneumocystis in mice. 1470 88


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