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)

4 wk after intraperitoneal inoculation of 0.2 LD50 (50% lethal dose) of murine cytomegalovirus (MCMV) in adult BALB/c mice, MCMV remained detectable in the salivary glands, but not in the lungs or other organs. When the T cells of these mice were activated in vivo by a single injection of anti-CD3 monoclonal antibody, interstitial pneumonitis was induced in the lungs that were free of the virus with an excessive production of the cytokines. In the lungs of such mice persistently infected with MCMV, the mRNA of the cytokines such as IL-2, IL-6, TNF-alpha, and IFN-gamma were abundantly expressed 3 h after the anti-CD3 injection, and the elevated levels continued thereafter. A marked expression of inducible nitric oxide synthetase (iNOS) was then noted in the lungs, suggesting that such cytokines as TNF-alpha and IFN-gamma may have induced iNOS. Although the increase in NO formation was demonstrated by the significant elevation of the serum levels of nitrite and nitrate, the interstitial pneumonitis was not associated with either increased superoxide formation or peroxynitrite-induced tyrosine nitration. Nevertheless, the administration of an NO antagonist also alleviated the interstitial pneumonitis provoked by anti-CD3 mAb. Based on these findings, it was concluded that MCMV-associated pneumonitis is mediated by a molecule of cytokine-induced NO other than peroxynitrite.
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PMID:Nitric oxide mediates murine cytomegalovirus-associated pneumonitis in lungs that are free of the virus. 931 83

Tumor necrosis factor-alpha (TNF-alpha) has been shown to stimulate the resistance of alveolar macrophages and neutrophils to Legionella pneumophila in vitro. To determine whether endogenous TNF-alpha is necessary for host defense against legionellosis in vivo, anti-TNF-alpha IgG or control IgG was administered to rats exposed to aerosolized L. pneumophila. Treatment with anti-TNF-alpha neutralized >90% of the intrapulmonary TNF-alpha response to infection, resulting in persistent pneumonitis and failure to clear L. pneumophila from the lungs. Depletion of TNF-alpha limited the recruitment of mononuclear cells to the lungs and resulted in a progressive increase in the proportion of alveolar macrophages that were infected; neutrophil recruitment and phagocytosis were not impaired. Both systemic and intrapulmonary IFN-gamma levels were significantly higher in rats depleted of TNF-alpha. These observations indicate that TNF-alpha is required for the prompt resolution of pneumonic legionellosis and point to a direct role for TNF-alpha in the activation of phagocytes.
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PMID:Antibody-mediated depletion of tumor necrosis factor-alpha impairs pulmonary host defenses to Legionella pneumophila. 933 61

The ongoing lung tissue damage in chronically Pseudomonas aeruginosa infected cystic fibrosis (CF) patients has been shown to be caused by elastase liberated from polymorphonuclear leukocytes (PMN), which dominate the chronic inflammation in these patients. Most CF patients, however, contract the chronic lung infection with P. aeruginosa after a one-year period (median) of intermittent colonization. Therefore, prevention of the onset of the chronic infection or prevention of the dominance of the inflammation by PMNs would be important goals for a vaccine strategy against P. aeruginosa in CF. In a rat model of acute P. aeruginosa pneumonia we studied whether it was possible to improve the initial bacterial clearance and diminish the inflammatory response by vaccination prior to challenge with free, live P. aeruginosa. The vaccines studied were PAO 579 sonicate, O-polysaccharide toxin A (TA) conjugate, depolymerized alginate (3064) TA conjugate (D-ALG TA), or P. aeruginosa alginate (6680 + 8839). The vaccines could, however, not improve the very efficient natural clearance of P. aeruginosa from the lungs of the rats. In a rat model of chronic P. aeruginosa lung infection we found that none of the vaccines could prevent chronic lung inflammation. After challenge, however, none of the rats immunized with D-ALG TA died in contrast to the other vaccine groups combined (p = 0.03). In addition, the inflammatory response changed from an acute type inflammation dominated by PMNs as in CF patients to a chronic type inflammation dominated by mononuclear leukocytes. This response was achieved within the first week after challenge in D-ALG TA immunized rats; in the controls, the inflammation was still acute 4 weeks after challenge. Rats immunized with D-ALG TA had a significantly reduced severity of the macroscopic lung inflammation compared to the other vaccination groups (p = 0.009). The same effect could be obtained by IFN-gamma treatment (p = 0.004). The chronic P. aeruginosa lung infection was established in two inbred mice strains C3H/HeN, known as TH1 responders, and Balb/c, known as TH2 responders. The mortality due to the infection was significantly lower in C3H/HeN mice compared to Balb/c mice (p < 0.0003). P. aerurinosa was cleared more efficiently by C3H/HeN mice and significantly more C3H/HeN mice showed normal lung histopathology than Balb/c mice (p < 0.025). Supernatants from Concanavalin A stimulated spleen cells from C3H/HeN mice contained three times higher IFN-gamma concentration but only half as high interleukin-4 concentration than those of Balb/c mice. These findings suggest that change from the TH2-like response seen in CF patients towards a TH1 response might improve their prognosis.
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PMID:Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia. A new prophylactic principle. 938 50

To determine whether different antibody isotypes associated with T helper 1 (Th1) or Th2 responses are protective against Pneumocystis carinii, mice with disrupted interleukin 4 genes (IL-4(-/-) mice) or gamma interferon genes (IFN-gamma(-/-) mice) along with wild-type C57BL/6 mice were immunized intratracheally against P. carinii, depleted of T cells in vivo by use of monoclonal antibodies, and rechallenged intratracheally with 10(7) viable P. carinii organisms. Nearly all immunized mice resolved their lung P. carinii infections (limit of detection, log10 4.06) within 21 days of challenge even though they were depleted of T cells. Unimmunized mice depleted of T cells had significant lung infections (>log10 5.5) at day 21 post-P. carinii challenge. IFN-gamma(-/-) and wild-type mice developed P. carinii-specific immunoglobulin primarily of the immunoglobulin G1 (IgG1) subclass with relatively little P. carinii-specific IgG2a, IgG2b, or IgG3 in their sera, characteristic of a Th2-type response. In contrast, IL-4(-/-) mice had primarily an IgG2b P. carinii-specific antibody response in their sera with very little IgG1. Although IgG2b was the predominant isotype in IL-4(-/-) mice, optical density values of IgG2a and IgG3 were significantly higher in these mice (two and three times, respectively) than in IFN-gamma(-/-) mice, characteristic of a Th1-type response. Together, these data indicate that resolution of P. carinii infection can be mediated by specific antibody responses and that the antibody response can be either a predominantly Th1 or Th2 type. Furthermore, although wild-type mice mounted a Th2-like antibody response, IL-4(-/-) mice could resolve P. carinii pneumonia, indicating that resistance to P. carinii can occur in the absence of IL-4.
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PMID:Protection against Pneumocystis carinii pneumonia by antibodies generated from either T helper 1 or T helper 2 responses. 939 95

Mycoplasma pneumoniae is a leading cause of pneumonia and exacerbates other respiratory diseases in humans. We investigated the potential role of surfactant protein (SP) A in antimycoplasmal defense using alveolar macrophages (AMs) from C57BL/6NCr (C57BL) mice, which are highly resistant to infections of Mycoplasma pulmonis. C57BL AMs, activated with interferon (IFN)-gamma and incubated with SP-A (25 micrograms/ml) at 37 degrees C, produced significant amounts of nitric oxide (.NO; nitrate and nitrite production = 1.1 microM.h-1.10(5) AMs-1) and effected an 83% decrease in mycoplasma colony-forming units (CFUs) by 6 h postinfection. Preincubation of AMs with the inducible nitric oxide synthase inhibitor NG-monomethyl-L-arginine abolished .NO production and SP-A-mediated killing of mycoplasmas. No decrease in CFUs was seen when IFN-gamma-activated macrophages were infected with mycoplasmas in the absence of SP-A despite significant .NO production (nitrate and nitrite production = 0.6 microM.h-1.10(5) AMs-1). These results demonstrate that SP-A mediates killing of mycoplasmas by AMs, possibly through an .NO-dependent mechanism.
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PMID:Surfactant protein A mediates mycoplasmacidal activity of alveolar macrophages. 948 13

Murine models of invasive candidiasis were used to study the in vivo importance of gamma interferon (IFN-gamma) and interleukin-4 (IL-4) in host defense against Candida albicans and to characterize the tissue inflammatory reactions, with special reference to macrophages (Mphi). Knockout (KO) IFN-gamma-deficient (GKO) and IL-4-deficient (IL-4 KO) and C57BL/6 parental mouse strains were challenged intraperitoneally with 10(8) C. albicans blastoconidia. Survival of GKO mice was significantly lower (16.7%) than that of C57BL/6 control (55.5%) and IL-4 KO (61.1%) animals, but was not correlated with the extent of organ colonization. Immunohistological analysis with a panel of myeloid and lymphoid markers revealed multiple renal abscesses, myocarditis, hepatitis, meningoencephalitis, and pneumonia in each strain, with a dominant presence of Mphi. In the absence of IFN-gamma, C. albicans induced striking changes in the phenotype of alveolar Mphi and extensive perivascular lymphoid infiltrates in the lung. Impairment in nitric oxide production by peritoneal Mphi was shown only in GKO mice, and they produced Candida-specific immunoglobulin G (IgG), IgM, IgA, and IgG subclasses in lower titers. Our in vivo studies with KO mice elucidate a critical role for IFN-gamma, but not IL-4, in host defense against C. albicans.
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PMID:Characteristics of invasive candidiasis in gamma interferon- and interleukin-4-deficient mice: role of macrophages in host defense against Candida albicans. 952 1

TNF-alpha exerts its biologic activity through two distinct receptors, TNF receptor type 1 (TNFR1, p55) and TNF receptor type 2 (TNFR2, p75). To analyze their function in toxoplasmosis, we orally infected mice genetically deficient for TNFR1 (TNFR1(0/0)), TNFR2 (TNFR2(0/0)), or both TNF receptors (TNFR1/2(0/0)), as well as wild-type (wt) mice with a low-virulent strain of Toxoplasma gondii. TNFR1/2(0/0) and TNFR1(0/0) mice succumbed to toxoplasmosis within 17 and 27 days, respectively, whereas TNFR2(0/0) and wt mice were equally resistant to acute toxoplasmosis. Histopathology attributed death of TNFR1/2(0/0) and TNFR1(0/0) mice to a fulminant necrotizing encephalitis. In addition, pneumonia contributed to the fatal outcome. The poor prognosis of TNFR1/2(0/0) and TNFR1(0/0) mice was reflected by a significantly increased parasitic load in the brain and lung as compared with TNFR2(0/0) and wt mice. Immunohistochemistry demonstrated a remarkable reduction of inducible nitric oxide synthase protein in brain and lung of TNFR1/2(0/0) and TNFR1(0/0) as compared with TNFR2(0/0) and wt mice. Reverse-transcribed PCR showed that in contrast to TNFR2(0/0) and wt mice, TNFR1(0/0) mice were unable to up-regulate inducible nitric oxide synthase mRNA transcripts in the course of infection, whereas intracerebral levels of IFN-gamma, TNF-alpha, and IL-1beta mRNA transcripts, recruitment of immune cells to the brain, and the amount of apoptotic cells in inflammatory foci did not differ significantly among the various experimental groups. These results illustrate that in Toxoplasma encephalitis, TNF-alpha-mediated immune responses are of crucial importance and that signaling through TNFR1, but not TNFR2, provides the stimulus required for the induction of protective nitric oxide.
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PMID:Crucial role of TNF receptor type 1 (p55), but not of TNF receptor type 2 (p75), in murine toxoplasmosis. 953 3

The aim of the present study was to further characterize the role of alveolar macrophages (AM) in acute human lung inflammation by evaluating their capacity to produce pro-inflammatory cytokines such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8. Patients with severe community-acquired pneumonia (CAP; n=12) and healthy volunteers (n=10) underwent bronchoalveolar lavage (BAL). AM were separated to high purity (>96%) using fluorescence-activated cell sorting. We determined the TNF-alpha, IL-6 and IL-8 cytokine gene expression in AM ex vivo using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Moreover, we measured in vitro unstimulated, lipopolysaccharide (LPS)- and LPS/interferon-gamma inducible TNF-alpha, IL-6 and IL-8 cytokine release and evaluated samples of BAL fluids for the same pro-inflammatory cytokines using an enzyme-linked immunosorbent assay (ELISA). We found increased TNF-alpha, IL-6 and IL-8 messenger ribonucleic acid (mRNA) levels in AM from CAP patients that were significantly elevated only for IL-8. When challenged with endotoxin in vitro, AM obtained from CAP patients showed a strongly reduced potential to release TNF-alpha and IL-6 compared to healthy controls, whereas IL-8 secretion did not differ significantly between groups. Moreover, stimulation of AM from CAP patients with LPS plus IFN-gamma augmented TNF-alpha and IL-6 cytokine release to near normal levels. Interestingly, no TNF-alpha protein was measured in BAL samples from CAP patients, whereas IL-6 and IL-8 protein levels were found to be significantly increased. Together, highly purified alveolar macrophages from community-acquired pneumonia patients show relatively low ex vivo tumour necrosis factor-alpha and interleukin-6 but not interleukin-8 messenger ribonucleic acid levels that are associated with a decreased pro-inflammatory cytokine release in vitro which, however, can be restored by concurrent interferon-gamma stimulation.
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PMID:Expression of pro-inflammatory cytokines by flow-sorted alveolar macrophages in severe pneumonia. 959 98

T cell-mediated immunity as measured by delayed-type hypersensitivity, and IFN-gamma production has been shown to be critical for host defense against Chlamydia trachomatis infection in both human and animal studies. Using gene-targeted B cell-deficient mice, we examined the role of B cells in protective immunity to C. trachomatis (mouse pneumonitis) (MoPn) lung infection. B cell-deficient mice were observed to have a significantly higher mortality rate and in vivo chlamydial growth than did wild-type mice following MoPn lung infection. Interestingly, B cell-deficient mice not only lacked Ab responses but also failed to mount an efficient delayed-type hypersensitivity response following chlamydial lung infection. In contrast to results obtained from MoPn-infected wild-type C57BL/6 mice, spleen cells from infected B cell-deficient mice failed to produce Th1-related (IFN-gamma) or Th2-related (IL-6 and IL-10) cytokines after Chlamydia-specific in vitro restimulation. Moreover, unlike wild-type mice, B cell-deficient mice were not immune to rechallenge infection following recovery from primary chlamydial infection. The data indicate that B cells play an important role in host defense to primary and secondary chlamydial infection and suggest that B cells are crucial for the initiation of early T cell responses to chlamydial infection. This study provides evidence for the role of B cells in the in vivo priming of T cells during infection with the intracellular bacterial pathogen, C. trachomatis.
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PMID:Gene knockout B cell-deficient mice demonstrate that B cells play an important role in the initiation of T cell responses to Chlamydia trachomatis (mouse pneumonitis) lung infection. 968 9

A whole-blood model was used to evaluate the effects of temperature and anticoagulant on the expression of activation markers HLA-DR and CD11b on peripheral leukocytes. Venous blood, anticoagulated with either EDTA or heparin, was obtained from six healthy blood donors and 13 hospitalized patients (8 human immunodeficiency virus type 1-seropositive individuals with concurrent pulmonary tuberculosis and 5 patients with pneumonia). A preliminary evaluation was carried out with whole blood from two of the normal donors, and cells were stained immediately for HLA-DR and CD11b markers or stained after incubation at room temperature or 37 degreesC for 18 h with or without the addition of the cytokines gamma interferon (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-gamma plus GM-CSF, tumor necrosis factor beta, or interleukin-6. Of the cytokines tested, the combination of IFN-gamma and GM-CSF had the most pronounced modulation of marker expression on polymorphonuclear neutrophils (PMN), in particular, HLA-DR expression, which required induction for its detection. These cytokines were therefore used in further evaluations that considered the above-mentioned effects in the presence of disease. Results indicated that the expression of activation markers on PMN and lymphocytes in whole blood are influenced by the temperature of incubation and the choice of anticoagulant and the effects noted were dependent on (i) the particular cell surface marker, (ii) the cell type being studied, and (iii) the presence or absence of disease. It is therefore recommended that ex vivo whole-blood models for evaluating phenotype or immune function be carefully evaluated for the above-mentioned effects.
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PMID:Effects of anticoagulants and temperature on expression of activation markers CD11b and HLA-DR on human leukocytes. 972 38


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