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

Mice were thymectomized and depleted of CD4+ lymphocytes by treatment with monoclonal antibody to induce Pneumocystis carinii (PC) pneumonia (PCP). These mice were then exposed to aerosols of heat-treated Escherichia coli three times a week. Aerosol treatment for 10 d caused a slight reduction in numbers of PC nuclei in the lungs of mice, and treatment for 22 d resulted in nearly complete resolution of PCP. Large numbers of macrophages, polymorphonuclear leukocytes, and lymphocytes accumulated in lungs of aerosol-treated mice. Depletion of either CD8+ lymphocytes or asialo GM1+ cells that remained in the mice after CD4+ cell depletion had no effect on the ability of the mice to resolve PCP after E. coli aerosol treatments. However, depletion of Thy-1+ lymphocytes in these mice abrogated their ability to resolve PCP and reduced the numbers of macrophages that accumulated in the lungs. In addition, it was found that resolution of PCP induced by heat-treated E. coli aerosol treatments was also abrogated when mice were treated with polyclonal antibodies against tumor necrosis factor alpha (TNF-alpha). Thus, resolution of PCP in CD4+ lymphocyte-depleted mice by heat-treated E. coli aerosols was not dependent on either CD8+ or asialo GM1+ cells but was dependent on Thy-1+CD4-CD8- lymphocytes and on the participation of TNF. These results indicate that heat-treated E. coli aerosols can act as an immune response modifier by inducing resolution of PCP in mice by a mechanism not dependent on the presence of CD4+ lymphocytes.
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PMID:Resolution of Pneumocystis carinii pneumonia in CD4+ lymphocyte-depleted mice given aerosols of heat-treated Escherichia coli. 135 3

C.B-17 scid/scid (SCID) mice that have acquired natural pulmonary infection with Pneumocystis carinii clear these organisms by 19 days after reconstitution with spleen cells from immunocompetent mice and therefore serve as a model for studying the pathogenesis of and immunity to P. carinii pneumonia. The present study examined the importance of endogenous tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) in the clearance of P. carinii by treatment of reconstituted SCID mice with anti-TNF-alpha and anti-IFN-gamma immunoglobulin G (IgG). Treatment of reconstituted mice with monospecific rabbit anti-TNF-alpha IgG almost completely inhibited the clearance of P. carinii from the lungs. In contrast, treatment with either anti-IFN-gamma antibody (polyclonal or monoclonal) or control IgG had no detectable effect on the clearance of P. carinii. The importance of endogenous TNF-alpha in the clearance of P. carinii was further supported by the finding of TNF-alpha but not IFN-gamma in lung homogenate supernatants from reconstituted SCID mice. Further study revealed that for the complete clearance of P. carinii, TNF-alpha must be present at the early stage of reconstitution, since clearance could be blocked by a single injection of anti-TNF-alpha IgG into SCID mice at day 0 but not at day 6 and/or day 12 after reconstitution. These results strongly suggest that, in reconstituted SCID mice, endogenous TNF-alpha is important in host resistance against P. carinii infection, whereas IFN-gamma appears not to play a significant role.
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PMID:Importance of endogenous tumor necrosis factor alpha and gamma interferon in host resistance against Pneumocystis carinii infection. 154 57

Alveolar macrophages (AMs) are important in the host response to aerogenous pulmonary bacterial infections, such as Pasteurella haemolytica-induced pneumonia in cattle. Previous work has shown that AMs enhance P. haemolytica-mediated pulmonary endothelial cell (EC) damage in vitro. The purpose of this study was to determine the mechanism of AM-enhanced EC damage using an in vitro AM-EC coculture system consisting of AMs cultured on culture plate insert membranes and ECs in the underlying chamber. The addition of lipopolysaccharide (LPS) to the culture plate insert chamber resulted in EC damage indicated by 51Cr release, which was enhanced in the presence of AMs. To determine the role of AM-secreted cytokines, recombinant human interleukin 1 alpha (IL-1) or tumor necrosis factor alpha (TNF) was added to ECs simultaneously with varying concentrations of LPS. Although TNF and IL-1 alone had only marginal toxic effects on ECs, the simultaneous treatment of TNF or IL-1 with LPS greatly increased the LPS cytotoxic effect on ECs. In addition, IL-1 receptor antagonist eliminated the IL-1 enhancement of LPS-mediated EC toxicity. These results suggest that macrophage-secreted cytokines synergistically enhance LPS-mediated pulmonary EC damage.
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PMID:Tumor necrosis factor alpha and interleukin 1 alpha enhance lipopolysaccharide-mediated bovine endothelial cell injury. 161 94

Soluble mediators such as tumor necrosis factor alpha (TNF-alpha) may be important in the pathogenesis of many chronic pulmonary infections. We examined the ability of Corynebacterium pseudotuberculosis, Pasteurella haemolytica, and ovine lentiviruses (OvLV) to induce TNF-alpha secretion by pulmonary alveolar macrophages (PAM). Bronchoalveolar lavage cells, composed of greater than 90% PAM, were obtained from normal sheep. Bronchoalveolar lavage cells were cultured for 2, 24, 48, 72, or 168 h in endotoxin-free RPMI medium (with 10% autologous serum) or in medium containing one of the following additives: lipopolysaccharide, 1-micron polystyrene beads, C. pseudotuberculosis, P. haemolytica, or one of two plaque-cloned OvLV, 85/28 or 85/34. Lipopolysaccharide, C. pseudotuberculosis, and P. haemolytica induced TNF-alpha activity in PAM cultures as early as 2 h after inoculation, as assessed by a colorimetric cytotoxicity assay. This activity could be blocked by rabbit anti-recombinant bovine TNF-alpha serum. In contrast, medium alone, polystyrene beads, and productive infection by OvLV did not induce TNF-alpha activity in PAM cultures. Bacterial pathogens which infect pulmonary macrophages may elicit the secretion of TNF-alpha within the lungs and lead to the cachectic state associated with chronic pneumonia.
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PMID:Differential induction of tumor necrosis factor alpha in ovine pulmonary alveolar macrophages following infection with Corynebacterium pseudotuberculosis, Pasteurella haemolytica, or lentiviruses. 165 61

Intranasal inoculation of type 5 adenovirus (Ad5) produced pneumonia in mice even though the virus did not replicate. To induce the pneumonia, however, a large viral infectious dose was required--i.e., 10(10) plaque-forming units. Four strains of inbred mouse were studied (C57BL/6N, C57BL/10ScN, CBA/N, and C3H/N): all showed similar inflammatory responses, although the greatest infiltration occurred in the C57BL/6N mice. The pathological response to Ad5 infection resembled that previously described in cotton rats: it consisted of overlapping early and late phases, and the infiltration contained primarily lymphocytes and monocytes/macrophages with a scattering of polymorphonuclear leukocytes. The prominent early phase and the presence of polymorphonuclear leukocytes suggested that induction of cytokines may play an important role in the pathogenesis of this pneumonia. Assays showed the appearance of tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), and IL-6 in the infected mouse lungs concomitant with the developing early-phase infiltration. Only IL-6 was found in the peripheral blood. IL-6 reached maximum titers 6-24 hr after infection, whereas maximum levels of TNF-alpha and IL-1 were attained 2-3 days after infection. Specific RNAs for each of these cytokines were demonstrated in the infected lungs. To test the hypothesis that a cytotoxic T-cell response was responsible for the second phase, which primarily consisted of a perivascular and peribronchial infiltration of lymphocytes, Ad5 was used to infect C57BL/10ScN Nu/Nu and parent mice. The nude mice showed a normal early-phase response, but essentially no peribronchial and only minimal perivascular infiltrations occurred.
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PMID:A mouse model for investigating the molecular pathogenesis of adenovirus pneumonia. 184 5

In a mouse model of pneumonia caused by murine Chlamydia trachomatis (mouse pneumonitis agent [MoPn]), tumor necrosis factor alpha (TNF-alpha) antigen and bioactivity were demonstrated in vivo in the lung during MoPn infection in both athymic (nude) and heterozygous (nu/+) mice. Antibody to TNF-alpha that was exogenously given neutralized the TNF-alpha in the lung, significantly accelerated mortality, and caused a borderline increase in MoPn counts in the lung by culture in nu/+ mice. Lipopolysaccharide-induced TNF-alpha activity or injections of recombinant murine TNF-alpha significantly but modestly protected nu/+ mice against MoPn-induced mortality. TNF-alpha is produced in vivo during C. trachomatis infection and plays a role in host defense.
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PMID:A role in vivo for tumor necrosis factor alpha in host defense against Chlamydia trachomatis. 234 Nov 67

A mouse model of pneumonia caused by murine Chlamydia trachomatis (mouse pneumonitis agent) was used to demonstrate that whole spleen cells from both nude athymic mice (nu/nu) and heterozygous mice (nu/+) produced tumor necrosis factor alpha in vitro in response to mouse pneumonitis agent antigen. The tumor necrosis factor alpha measured in these supernatants by immunoassay was shown to have bioactivity in a cytotoxic assay in which uninfected target cells were used. This cytotoxicity was distinct from the gamma interferon-related cytotoxicity against C. trachomatis-infected targets that we described previously.
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PMID:Tumor necrosis factor alpha is a cytotoxin induced by murine Chlamydia trachomatis infection. 270 49

A murine pulmonary model was used to study the mucosal immune response to Shigella flexneri serotype 2a infection. Inoculation of BALB/cJ mice with shigellae via the intranasal route resulted in bacterial invasion of bronchial and alveolar epithelia with concomitant development of acute suppurative bronchiolitis and subsequent development of lethal pneumonia. The pathology of pulmonary lesions resembled the colitis that characterizes shigellosis in humans and primates. Significant protection against a lethal dose of S. flexneri 2a was observed in mice previously infected with two sublethal doses of the homologous strain. Immunity against lethal challenge was associated with decreased bacterial invasion of the mucosal epithelium. Over the course of two sublethal challenges, which constituted primary and secondary immunizations, mice developed pulmonary and serum immunoglobulin G and A antibody recognizing both lipopolysaccharide and invasion plasmid antigens IpaB and IpaC. Immune mice and naive control mice differed in lung lavage cytokine levels following lethal challenge. Immune mice developed significantly elevated levels of pulmonary gamma interferon within 6 h of challenge, while naive control mice developed elevated levels of this cytokine later during the initial 24-h period. Both groups had elevated levels of gamma interferon during the 24- to 48-h period of infection. Both groups also had elevated levels of tumor necrosis factor alpha within 6 h of challenge, but the control mice had significantly higher levels at the 48- and 72-h time points. Elevated levels of interleukin-4 were observed only in immunized mice. This cytokine appeared within 24 h and receded between 48 and 72 h. Fluorescence-activated cell sorter analysis of lung parenchymal cells showed that both groups experienced an initial influx of monocytes, but the proportion of this cell type began to recede in immunized mice after 48 h of infection, while peak levels were maintained in the control animals. These studies suggest that elements of local B lymphocyte activity, as well as Th1 and Th2 lymphocyte activity, may contribute to the survival of immune mice after intranasal challenge with shigellae.
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PMID:Antibody and cytokine responses in a mouse pulmonary model of Shigella flexneri serotype 2a infection. 772 7

The role of CD8+ T cells in antichlamydial immunity was investigated in a murine model of chlamydial genital infection by using T-cell clones generated against the Chlamydia trachomatis agent of mouse pneumonitis (MoPn). Two CD8+ T-cell clones tested (2.1F and 2.14-9) were chlamydia antigen specific and MHC restricted and reacted against MoPn as well as the Chlamydia psittaci agent of guinea pig inclusion conjunctivitis and C. trachomatis serovar E, suggesting the recognition of a genus-specific antigen. Upon adoptive transfer into persistently MoPn-infected nu/nu mice, 55.6% of the recipients of clone 2.1F (15 of 27) resolved the infection but recipients of clone 2.14-9 did not. The ability to resolve the MoPn infection correlated with the capacity of clone 2.1F to elaborate a combination of gamma interferon and tumor necrosis factor alpha. The results suggested that in addition to CD4+ T cells, CD8+ T cells may also contribute to antichlamydial T-cell immunity in vivo.
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PMID:Role for CD8+ T cells in antichlamydial immunity defined by Chlamydia-specific T-lymphocyte clones. 792 6

ICR mice were infected intranasally with Mycoplasma pulmonis isolated freshly from the lungs of a rat with pneumonia. We demonstrated with high reproducibility the expressions of messenger RNAs of cytokines, tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) in the lung tissue of M. pulmonis-infected mice by the reverse transcriptase-polymerase chain reaction and confirmed specific mRNA of the cytokines by restriction endonuclease digestion. Both the viable population of M. pulmonis in the lung tissue and the titers of the neutralizing antibody in the serum increased between 7 and 21 days, and reached their maximum 35 days after infection. The pneumonia in mice progresses with the development of lung lesions after 7 days of infection. The early lesions are characterized primarily by neutrophils and edema in the alveolar spaces. mRNAs prepared from the lung tissue of M. pulmonis-infected and -uninfected mice were also tested for the presence of messages specific to TNF alpha and IFN gamma by the reverse transcriptase-polymerase chain reaction. The expression of the genes encoding TNF alpha and IFN gamma was constitutively demonstrated from 24 hr through 35 days after the intranasal inoculation of M. pulmonis. Furthermore, cells of two types, adherent and nonadherent cells, in bronchoalveolar lavage fluids obtained from the mice 3 weeks after inoculation of M. pulmonis were also found to express the genes of TNF alpha and IFN gamma respectively. These data suggest that these cytokines would play a role in both stimulation in the development of pathological changes in mycoplasmal infection, affecting the inflammatory responses.
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PMID:Gene expression of tumor necrosis factor alpha and interferon gamma in the lungs of Mycoplasma pulmonis-infected mice. 793 58


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