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)

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

Circulating interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were examined in 42 febrile children with fever lasting more than 4 days. Their diagnosis were probable viral syndrome in 22, urinary tract infection (UTI) in 10, and probable bacterial pneumonia in 10. None of our study patients had detectable serum IL-1 beta. TNF-alpha levels were significantly higher in children with pneumonia than in those with viral syndrome (p < 0.01). Children with UTI and pneumonia had significantly higher IL-6 and CRP, compared to those with probable viral syndrome (p < 0.01 for both IL-6 and CRP). When appropriate cutoff values are chosen, IL-6 had greatly improved specificity (86.4%, > 20 pg/ml) to demonstrate UTI and pneumonia, as compared to that using CRP (48%, > 40 mg/l). After three days' antibiotic treatment, IL-6 fell to control levels in children with UTI and pneumonia, while CRP remained elevated. There was no difference in TNF-alpha values before and after treatment. Thus, IL-6, rather than IL-1 beta and TNF-alpha, may be a helpful diagnostic tool for evaluation of pediatric febrile infection. Sequential studies involving more patients are needed to determine whether IL-6 is better than CRP in this clinical setting.
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PMID:Circulating interleukin (IL)-1 beta, IL-6 and tumor necrosis factor-alpha in children with febrile infection--a comparison with C-reactive protein. 987 48

Protection against infections with the intracellular bacterium Chlamydia spp. requires Th1-polarized CD4+ T cell immunity. In BALB/c mouse lung infections, immediate innate and nascent Chlamydia-specific immune responses following intranasal inoculation of Chlamydia psittaci strain B577 were modulated by 7-day i.p. administration of murine rIL-12, the initiation cytokine for Th1 immunity. Treatment with IL-12 reduced the severity of chlamydial pneumonia, abolished mortality (37.5% in untreated mice), and significantly reduced numbers of chlamydial organisms in lungs. On day 4 after inoculation, the neutrophil:macrophage ratio in bronchointerstitial pneumonias was 1.96 in untreated mice and 0.51 in IL-12-treated mice. This immediate, IL-12-mediated shift in innate inflammatory phenotype was correlated with a significant reduction of lung concentrations of the neutrophil chemoattractant macrophage inflammatory protein (MIP)-2 (putative murine homologue of human IL-8), monocyte chemotactic protein-1, and TNF-alpha; and a reduction in MIP-1alpha and IFN-gamma, at high-dose infection only, and IL-12-independent IL-10 levels. Chlamydia-specific Ab titers and Ig isotype ratios indicated an IL-12-dependent Th1 shift. Recall responses of IL-12-primed mice to secondary chlamydial lung infection eliminated chlamydiae more effectively and generated a lung cytokine profile conducive to perpetuation of the Th1 memory population. These data support the hypothesis that genetic differences in endogenous IL-12 production and response pathways could determine disease outcomes characterized by poor chlamydial clearance and a purulent inflammatory infiltrate vs effective elimination of chlamydiae in a macrophage-dominated response.
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PMID:IL-12 administered during Chlamydia psittaci lung infection in mice confers immediate and long-term protection and reduces macrophage inflammatory protein-2 level and neutrophil infiltration in lung tissue. 997 97

Drug can cause various types of lung damages, with drug-induced pneumonitis (including acute interstitial pneumonia, usual interstitial pneumonia, desquamative interstitial pneumonia, nonspecific interstitial pneumonia, bronchiolitis obliterans with organizing pneumonia, eosinophilic pneumonia and hypersensitivity pneumonitis) being the most important among them. The incidence and the causative agents of drug induced pneumonitis have varied over time. Before 1980, anticancer agents and gold salts were the main drugs, and the number of causative drugs (61) and case reports was small. Recently, pneumonitis has increasingly been caused by Chinese herbal medicines, antibiotics, chemotherapy agents, anti-inflammatory drugs, analgesics, cytokines, and gold salts, and the number of case reports and drugs involved (177) has increased. Drug-induced pneumonitis has characteristics that depend on the causative agent. Review of our patients and reports in Japan revealed the following. Pneumonitis caused by anti-inflammatory drugs, analgesics, and antibiotics generally develops at 1-2 weeks after starting administration, and bronchoalveolar lavage and histologic examination of lung biopsies reveals the features of eosinophilic pneumonia. Such pneumonitis is associated with a high frequency of a positive drug lymphocyte stimulation test (DLST), and has a good outcome. Conversely, with pneumonitis caused by anticancer and immunosuppressive agents, the onset is often delayed and the disease has features of diffuse interstitial pneumonia and pulmonary fibrosis. The frequency of a positive DLST is low, and the outcome is generally poor. Pneumonitis induced by Chinese herbal medicines, gold salts, and antituberculosis agents has intermediate features between the above two types :i.e., it develops after 2-3 months or six months (gold salts), and resembles either eosinophilic pneumonia, BOOP or interstitial pneumonia. For in vitro identification of causative drugs, the DLST and the leukocyte migration inhibition test (LMIT) are generally used. The latter test is superior in sensitivity, suggesting that the mechanism of this test involves cytokines such as IL-1 alpha, IL-1 beta, IL-2, TNF-alpha, and IL-8.
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PMID:[Drug-induced pneumonitis]. 1006 54

Resistance to the mouse pneumonitis (MoPn) strain of Chlamydia trachomatis has been mapped to MHC class II-restricted, IL-12-dependent CD4+ T cells that secrete a type 1 profile of proinflammatory cytokines, which includes IFN-gamma and TNF-alpha. The relative contribution of IFN-gamma is controversial, however, due to variation in results presented by different laboratories. To determine whether C. trachomatis strain differences contributed to this apparent conflict, the relative resistance of IFN-gamma-deficient mice to murine and human strains of C. trachomatis was compared. All human serovars were much more sensitive to the direct inhibitory actions of IFN-gamma than the MoPn strain. Furthermore, genital clearance of human serovar D in the C57BL/6 mouse was mediated by class II-independent mechanisms that probably involved local production of IFN-gamma by cells of the innate immune system. TNF-alpha also contributed indirectly to host resistance against all strains tested. The differential susceptibility of distinct C. trachomatis strains to effector cytokines such as IFN-gamma could not have been predicted by interstrain biologic variation or by the profile of cytokines stimulated during infection. These findings indicate that strain variation should be considered in situations where related isolates of a given parasite produce conflicting data in models of infection and immunity. They also suggest that stimulation of mucosal IFN-gamma activity is a relevant goal for a human chlamydial vaccine.
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PMID:Differential sensitivity of distinct Chlamydia trachomatis isolates to IFN-gamma-mediated inhibition. 1009 12

Previous studies have shown that high pleural fluid (Pf) hyaluronan (HYA) concentrations may be due not only to malignant mesothelioma but also to inflammatory diseases. The objective of this study was to evaluate Pf-HYA in various nonmalignant inflammatory pleural disorders. A radiometric assay was used to determine HYA in Pf and serum (S) of 126 patients, 12 of whom had rheumatoid arthritis (RA), 22 tuberculosis, 22 pneumonia, 41 lung cancer, 10 malignant mesothelioma and 19 congestive heart failure. Pf-HYA values were correlated with values for Pf-tumour necrosis factor (TNF)-alpha and Pf-interleukin (IL)-1beta, as determined by radioimmunoassay. The highest median Pf-HYA (125.6 mg x L(-1), range 0.04-386.5 mg x L(-1)) occurred in patients with malignant mesothelioma. Among patients with nonmalignant inflammatory diseases, significantly higher median Pf-HYA were observed in those with rheumatoid arthritis (64.2 mg x L(-1), range 25.8-106.9 mg x L(-1)) than in those with tuberculosis (25.5 mg x L(-1), range 14.9-57.1 mg x L(-1), p<0.0005) or pneumonia (20.9 mg x L(-1), range 9.5-129.4 mg x L(-1), p<0.005). There was no correlation between Pf-HYA and S-HYA. Pf-HYA correlated positively with Pf-TNF-alpha (r=0.62) and Pf-IL-1beta (r=0.52). High pleural fluid hyaluronan occurs not only in malignant mesothelioma, but also in certain nonmalignant inflammatory diseases, especially rheumatoid arthritis. One explanation for the increase in pleural fluid hyaluronan may be local production of proinflammatory cytokines, such as tumour necrosis factor-alpha and interleukin-1beta.
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PMID:High pleural fluid hyaluronan concentrations in rheumatoid arthritis. 1023 19

Radiation pneumonitis remains a critical dose-limiting toxicity of total body irradiation (TBI) for use in bone marrow transplantation. The acute and chronic phases of radiation damage in the mouse lung have been shown to correlate with mouse strain genotype and are dependent on fraction size, total dose, and total lung volume. Our prior studies demonstrated effective prevention of irradiation-induced lung damage and improved survival in C57BL/6J mice by MnSOD plasmid/liposome gene therapy. In the present studies, we investigated the kinetics of irradiation-induced upregulation of mRNA for acute phase cytokines interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, and fibrosis-associated transforming growth factor (TGF)-beta and isoforms (TGF-beta1, TGF-beta2 and TGF-beta3) in 2000 cGy whole-lung irradiated C57BL/6J mice, a strain known to develop dose and volume-dependent organizing alveolitis/fibrosis. The results demonstrate increase in mRNA for IL-1 between days 1 and 14 after irradiation with return to baseline levels out to 120 days. TNF-alpha mRNA levels were not initially elevated but increased between 80 and 100 days and then decreased by 120 days. The mRNA levels for TGF-beta1 demonstrated an initial increase within the first 14 days after total lung irradiation with a decrease to baseline levels out to 100 days. Then, in striking contrast to the other two cytokines, an increase in TGF-beta2 mRNA occurred at around 120 days and correlated with the detection of organizing alveolitis/radiation fibrosis and mortality. These results are consistent with a two-phase mechanism in the molecular pathology of irradiation lung injury, in which IL-1 cytokine mRNA levels correlated with the acute pneumonitis phase and delayed elevation of TNF-alpha (80-100 days), TGF-beta1 (100 days), and TGF-beta2 (120 days) were associated with the fibrosis phase. Insight into the cell-specific and tissue-specific molecular mechanisms of ionizing irradiation induction of mRNA for pulmonary cytokines may provide new strategies for treatment of radiation pneumonitis in TBI patients.
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PMID:Manganese [correction of Magnesium] superoxide dismutase (MnSOD) plasmid/liposome pulmonary radioprotective gene therapy: modulation of irradiation-induced mRNA for IL-I, TNF-alpha, and TGF-beta correlates with delay of organizing alveolitis/fibrosis. 1046

The aim of the study was to assess the potential role of glucocorticoids (GC) in modulating systemic and pulmonary inflammatory responses in mechanically ventilated patients with severe pneumonia. Twenty mechanically ventilated patients with pneumonia treated at a respiratory intensive care unit (RICU) of a 1,000-bed teaching hospital were prospectively studied. All patients had received prior antimicrobial treatment. Eleven patients received GC (mean+/-SD dose of i.v. methylprednisolone 677+/-508 mg for 9+/-7 days), mainly for bronchial dilatation. Serum and bronchoalveolar lavage fluid (BALF) tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and C-reactive protein levels were measured in all patients. The inflammatory response was attenuated in patients receiving GC, both systemically (IL-6 1,089+/-342 versus 630+/-385 pg x mL(-1), p=0.03; C-reactive protein 34+/-5 versus 19+/-5 mg x L(-1), p=0.04) and locally in BALF (TNF-alpha 118+/-50 versus 24+/-5 pg x mL(-1), p= 0.05; neutrophil count: 2.4+/-1.1 x 10(9) cells x L(-1) (93+/-3%) versus 1.9+/-1.8 x 10(9) cells x L(-1) (57+/-16%), p=0.03). Four of the 11 (36%) patients receiving GC died compared to six (67%) who were not receiving GC (p=0.37). The present pilot study suggests that glucocorticoids decrease systemic and lung inflammatory responses in mechanically ventilated patients with severe pneumonia receiving antimicrobial treatment.
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PMID:Role of glucocorticoids on inflammatory response in nonimmunosuppressed patients with pneumonia: a pilot study. 1048 55

The pathogenesis of septic shock occurring after Pseudomonas aeruginosa pneumonia was studied in a rabbit model. The airspace instillation of the cytotoxic P. aeruginosa strain PA103 into the rabbit caused a consistent alveolar epithelial injury, progressive bacteremia, and septic shock. The lung instillation of a noncytotoxic, isogenic mutant strain (PA103DeltaUT), which is defective for production of type III secreted toxins, did not cause either systemic inflammatory response or septic shock, despite a potent inflammatory response in the lung. The intravenous injection of PA103 did not cause shock or an increase in TNF-alpha, despite the fact that the animals were bacteremic. The systemic administration of either anti-TNF-alpha serum or recombinant human IL-10 improved both septic shock and bacteremia in the animals that were instilled with PA103. Radiolabeled TNF-alpha instilled in the lung significantly leaked into the circulation only in the presence of alveolar epithelial injury. We conclude that injury to the alveolar epithelium allows the release of proinflammatory mediators into the circulation that are primarily responsible for septic shock. Our results demonstrate the importance of compartmentalization of inflammatory mediators in the lung, and the crucial role of bacterial cytotoxins in causing alveolar epithelial damage in the pathogenesis of acute septic shock in P. aeruginosa pneumonia.
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PMID:Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia. 1049 9


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