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

Mortality after influenza is often due to secondary bacterial pneumonia with Streptococcus pneumoniae, particularly in the elderly. The reasons for the high fatality rate seen with this disease are unclear. To further characterize the pathogenesis of pneumonia after influenza in a mouse model, we examined the pathology and immunology that leads to fatal infection. Influenza-infected mice were either euthanized 24 h after secondary infection with S. pneumoniae for determination of pathology, bacterial cultures, and levels of immune effectors or were followed by use of a live imaging system for development of pneumonia. Influenza-infected mice challenged with each of 3 serotypes of pneumococcus developed a severe, necrotic pneumonia and met endpoints for euthanasia in 24 to 60 h. Strikingly elevated levels of both pro- and anti-inflammatory molecules including interleukins 6 and 10, macrophage inflammatory protein 1alpha, and chemokine KC were present in the blood. High levels of these cytokines and chemokines as well as tumor necrosis factor alpha, interleukin 1beta, and heme oxygenase 1 were present in the lungs, accompanied by a massive influx of neutrophils. Mortality correlated with the development of pneumonia and lung inflammation but not with bacteremia. This model has the potential to help us understand the pathogenesis of severe lung infections.
 ...
PMID:Induction of pro- and anti-inflammatory molecules in a mouse model of pneumococcal pneumonia after influenza. 1734 95

The host immune/inflammatory response following CNS infection by Klebsiella pneumoniae remains poorly understood. Using a rat model of K. pneumoniae meningoencephalitis, we investigated the temporal profiles of brain proinflammatory cytokines and their cellular sources. Leukocyte counts significantly increased in cerebrospinal fluid (CSF) at 2 h after K. pneumoniae inoculation into the rat brain but were still much lower than blood leukocyte counts. However, concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in CSF were much higher than the simultaneously collected serum levels. The rapid increase in brain expression of these cytokines at the messenger RNA (mRNA) and protein levels occurred earlier than the onset of leukocytosis. Double immunofluorescence staining revealed the presence of TNF-alpha, IL-1beta, and IL-6 in astrocytes and microglia. Exposure of primary culture of glial cells to K. pneumoniae also resulted in time-dependent increases in the concentration of these cytokines in the culture media. Taken together, our results suggest that glial cells are an important early source of proinflammatory cytokines during K. pneumonia infection of CNS.
 ...
PMID:Rapid glia expression and release of proinflammatory cytokines in experimental Klebsiella pneumoniae meningoencephalitis. 1739 34

Numerous studies have described that an initial injury alters immune function, disposing the injured subject to infectious complications. The mechanisms by which an initial injury primes the subject, exacerbating the responses to a second injury, remain unclear; however, inflammatory cytokines have been implicated. The development of "2-hit" models has allowed investigators to determine the role of inflammatory mediators in susceptibility to infection after injury. A high incidence rate of pneumonia after burn injury and a significant increase in postburn mortality led us to develop models of either Gram-positive (Streptococcus pneumoniae) or Gram-negative (Klebsiella pneumoniae) sepsis after burn injury on 40% of total body surface area in rodents. In this present model, we used adult Sprague-Dawley rats to evaluate cardiac function in vitro (using Langendorff method) and myocardial inflammation (myocyte secretion of cytokines measured using enzyme-linked immunosorbent assay) after burn complicated by sepsis. Either burn injury alone or sepsis alone produced myocardial inflammatory responses and contractile dysfunction. Either Gram-negative or Gram-positive infection exacerbated the myocardial inflammation (increased myocyte secretion of tumor necrosis factor alpha, interleukin 1beta, and interleukin 6) above that which occurred with burn alone or with infection alone. Burn complicated by sepsis exacerbated the myocardial contraction and relaxation defects observed with either sepsis alone or burn alone. Inasmuch as sepsis, which occurs after a previous injury, increases myocardial inflammation/dysfunction and mortality, the development of therapeutic strategies that either decrease inflammatory response to the initial injury or provide cardiac support during the postinjury period may improve the outcome in injured patients who are at risk for developing sepsis.
 ...
PMID:A model of myocardial inflammation and dysfunction in burn complicated by sepsis. 1752 9

Acinetobacter baumannii has emerged as a major cause of both community-associated and nosocomial pneumonia, but little is known about the cellular and molecular mechanisms of host defense against respiratory infection with this bacterial pathogen. In this study, we examined the role of neutrophils in host resistance to pulmonary A. baumannii infection in a mouse model of intranasal (i.n.) infection. We found that neutrophils were rapidly recruited to the lungs following i.n. inoculation of the pathogen and declined to baseline level upon clearance of the infection. Depletion of neutrophils using monoclonal antibody RB6-8C5 prior to infection resulted in an acute lethal infection that was associated with enhanced bacterial burdens in the lung (P < 0.05) and extrapulmonary dissemination to the spleen. The increased susceptibility to A. baumannii in neutropenic mice was associated with a delay in the mRNA expression and production of early proinflammatory cytokines such as tumor necrosis factor alpha, interleukin-6, keratinocyte chemoattractant protein, monocyte chemoattractant protein 1, and macrophage inflammatory protein 2 (MIP-2) in the lungs and development of severe bronchopneumonia and lymphoid tissue destruction in the spleen. Moreover, i.n. administration of the neutrophil-inducing chemokine MIP-2 to normal mice induced a pulmonary influx of neutrophils and significantly enhanced the clearance of A. baumannii from the lungs (P < 0.01). These results imply that neutrophils play a critical role in host resistance to respiratory A. baumannii infection.
 ...
PMID:Neutrophils play an important role in host resistance to respiratory infection with Acinetobacter baumannii in mice. 1790 7

Mycoplasma pneumoniae is a leading cause of pneumonia and is associated with asthma. Evidence links M. pneumoniae respiratory disease severity with interleukin-12 (IL-12) concentrations in respiratory secretions. We evaluated the effects of IL-12 therapy on microbiologic, inflammatory, and pulmonary function indices of M. pneumoniae pneumonia in mice. BALB/c mice were inoculated with M. pneumoniae or SP4 broth. Mice were treated with intranasal IL-12 or placebo daily for 8 days, starting on day 1 after inoculation. Mice were evaluated at baseline and on days 1, 3, 6, and 8 after therapy. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic score (HPS), BAL cytokine concentrations determined by enzyme-linked immunosorbent assay (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, and granulocyte-macrophage colony-stimulating factor), and plethysmography, both before and after methacholine treatment. M. pneumoniae-infected mice treated with IL-12 (MpIL12 mice) were found to have significantly higher BAL M. pneumoniae concentrations than those of M. pneumoniae-infected mice treated with placebo (MpP mice) (P < 0.001). MpIL12 mice had higher BAL concentrations of IL-12, IFN-gamma, TNF-alpha, and IL-6, with differences in IL-12 and IFN-gamma concentrations reaching statistical significance (P < 0.001). Airway obstruction was statistically elevated in MpIL12 mice compared to that in MpP mice (P = 0.048), while airway hyperreactivity was also elevated in MpIL12 mice but did not reach statistical significance (P = 0.081). Lung parenchymal pneumonia subscores were significantly higher in MpIL12 mice (P < 0.001), but no difference was found for overall HPS, even though a strong trend was noticed (P = 0.051). Treatment of experimental M. pneumoniae pneumonia with intranasal IL-12 was associated with more severe pulmonary disease and less rapid microbiologic and histological resolution.
 ...
PMID:Intranasal interleukin-12 therapy inhibits Mycoplasma pneumoniae clearance and sustains airway obstruction in murine pneumonia. 1803 33

Bacterial alveolar invasion is followed by an inflammatory response. A systemic extension of the compartmentalized immune response has been described in patients with severe pneumonia. The data suggest that some antimicrobials may induce a differential release of cytokines. We conducted a prospective, randomized study in adult patients with severe pneumococcal pneumonia to measure the effects of ceftriaxone and levofloxacin in the systemic cytokine expression over time. Demographic, clinical characteristics, and severity scores were recorded. The serum concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8, IL-10, and IL-1 receptor agonist were measured at 0, 24, 72, and 120 h. A total of 32 patients were included in the study. Both groups were homogeneous in terms of age, comorbidities, severity of disease, and corticosteroid or statin use. With the single exception of IL-1beta, all cytokines were detected in venous blood. All of the cytokines studied showed a similar pattern of progressive decrease over time. No significant differences in the concentrations of any of the cytokines studied were found, with the exception of TNF-alpha, for which lower concentrations were obtained at 120 h in the levofloxacin group (P = 0.014). Basal oxygen saturation (P = 0.034) and heart rate (P = 0.029) returned to normal values earlier in the levofloxacin arm. We demonstrated that in patients with severe pneumococcal pneumonia pro- and anti-inflammatory responses could be detected in venous blood, representing a systemic extension of the compartmentalized response. Treatment with a beta-lactam agent or a fluoroquinolone has different effects on cytokine production and its systemic expression, impacting the clinical course of the disease.
 ...
PMID:Systemic expression of cytokine production in patients with severe pneumococcal pneumonia: effects of treatment with a beta-lactam versus a fluoroquinolone. 1842 93

Infection of mice with pneumonia virus of mice (PVM) is used as a natural host experimental model for studying the pathogenesis of infection with the closely related human respiratory syncytial virus. We analyzed the contribution of T cells to virus control and pathology after PVM infection. Control of a sublethal infection with PVM strain 15 in C57BL/6 mice was accompanied by a 100-fold increase in pulmonary cytotoxic T lymphocytes, 20% of which were specific for PVM. T-cell-deficient mice failed to eliminate PVM and became virus carriers in the absence of the clinical or histopathological signs of pneumonia that occurred after infection of control mice. Mice with limited T-cell numbers did not achieve virus control without weight loss, indicating that T-cell-mediated virus control was closely linked to immunopathology. Both CD4 and CD8 T cells independently contributed to virus elimination and disease. Virus control and disease were similar in the absence of perforin, gamma interferon, or tumor necrosis factor alpha. Interestingly, disease and mortality after lethal high-dose PVM infection were independent of T cells. These data illustrate a key role for T cells in control of PVM infection and demonstrate that both T-cell-dependent and -independent pathways contribute to disease in a viral dose-dependent fashion.
 ...
PMID:Role of T cells in virus control and disease after infection with pneumonia virus of mice. 1881 8

Rhodococcus equi is an intracellular pathogen of macrophages that causes rhodococcal pneumonia in foals and immunocompromised people. Evidence exists that neutrophils play a vital role in resistance to infection with R. equi; however, the means by which neutrophils exert their effects have not been clearly defined. In addition to directly killing bacteria, neutrophils also may exert a protective effect by linking innate and adaptive immune responses. In the present study we evaluated the cytokine expression profiles of adult equine neutrophils in response to stimulation with isogenic strains of virulent and avirulent R. equi in vitro. After 2 and 4h incubation with virulent or avirulent R. equi, adult equine neutrophils expressed significantly (P<0.05) greater tumor necrosis factor alpha (TNFalpha), interleukin (IL)-12p40, IL-6, IL-8 and IL-23p19 mRNA, but not interferon gamma (IFNgamma) or IL-12p35 mRNA than unstimulated neutrophils. Furthermore, virulent R. equi induced significantly greater IL-23p19 mRNA than avirulent R. equi. These results demonstrate that R. equi-stimulated neutrophils are a source of many proinflammatory cytokines. Furthermore, these results suggest that IL-23 may be preferentially expressed over IL-12 in response to exposure with R. equi, and that this response may be more strongly induced by virulent R. equi than avirulent R. equi. Collectively, the data presented herein suggest a non-phagocytic role for neutrophils that may influence the type of adaptive immune response to R. equi.
 ...
PMID:Cytokine expression by neutrophils of adult horses stimulated with virulent and avirulent Rhodococcus equi in vitro. 1901 57

Respiratory syncytial virus (RSV) is a common cause of infection that is associated with a range of respiratory illnesses, from common cold-like symptoms to serious lower respiratory tract illnesses such as pneumonia and bronchiolitis. RSV is the single most important cause of serious lower respiratory tract illness in children <1 year of age. Host innate and acquired immune responses activated following RSV infection have been suspected to contribute to RSV disease. Toll-like receptors (TLRs) activate innate and acquired immunity and are candidates for playing key roles in the host immune response to RSV. Leukocytes express TLRs, including TLR2, TLR6, TLR3, TLR4, and TLR7, that can interact with RSV and promote immune responses following infection. Using knockout mice, we have demonstrated that TLR2 and TLR6 signaling in leukocytes can activate innate immunity against RSV by promoting tumor necrosis factor alpha, interleukin-6, CCL2 (monocyte chemoattractant protein 1), and CCL5 (RANTES). As previously noted, TLR4 also contributes to cytokine activation (L. M. Haynes, D. D. Moore, E. A. Kurt-Jones, R. W. Finberg, L. J. Anderson, and R. A. Tripp, J. Virol. 75:10730-10737, 2001, and E. A. Kurt-Jones, L. Popova, L. Kwinn, L. M. Haynes, L. P. Jones, R. A. Tripp, E. E. Walsh, M. W. Freeman, D. T. Golenbock, L. J. Anderson, and R. W. Finberg, Nat. Immunol. 1:398-401, 2000). Furthermore, we demonstrated that signals generated following TLR2 and TLR6 activation were important for controlling viral replication in vivo. Additionally, TLR2 interactions with RSV promoted neutrophil migration and dendritic cell activation within the lung. Collectively, these studies indicate that TLR2 is involved in RSV recognition and subsequent innate immune activation.
 ...
PMID:Respiratory syncytial virus activates innate immunity through Toll-like receptor 2. 1901 63

Mycoplasma pneumoniae is one of the causative agents of atypical community-acquired pneumonia. Tigecycline belongs to a new class of glycylcycline antimicrobials that have activity against a wide range of microorganisms, including in vitro activity against M. pneumoniae. We investigated the effect of tigecycline on microbiologic, histologic, and immunologic indices in a murine model of M. pneumoniae pneumonia. BALB/c mice were inoculated intranasally with M. pneumoniae and treated subcutaneously with tigecycline or placebo for 6 days. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic score (HPS), BAL cytokine and chemokine concentrations (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], interleukin 1beta [IL-1beta], IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 [p40/p70], granulocyte-macrophage colony-stimulating factor, MIP-1alpha, MIG, KC, MCP-1, and IP-10). BAL M. pneumoniae concentrations in mice treated with tigecycline (MpTige) tended to be reduced compared with mice treated with placebo (MpPl); however this did not reach statistical significance. The lung HPS was significantly lower, as well as the parenchymal-pneumonia subscore, in the MpTige mice than in the MpPl mice. MpTige mice had significantly lower BAL cytokine concentrations of IL-1beta, IL-12 (p40/p70), IFN-gamma, and TNF-alpha; of the chemokines, MIG, MIP-1alpha, and IP-10 were statistically lower in MpTige mice. While tigecycline treatment demonstrated a modest microbiologic effect, it significantly improved lung histologic inflammation and reduced pulmonary cytokines and chemokines.
 ...
PMID:Tigecycline therapy significantly reduces the concentrations of inflammatory pulmonary cytokines and chemokines in a murine model of Mycoplasma pneumoniae pneumonia. 1913 87


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>