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)

The objective of this pilot study was to compare the cytokine profile as well as cell-mediated and antibody responses of foals infected with a low inoculum of virulent Rhodococcus equi resulting in subclinical pneumonia to that of foals infected with a high inoculum resulting in severe clinical pneumonia. The mean (+/-SD) ratio of post-infection to pre-infection anti-R. equi IgG(T) concentration was significantly (P=0.002) higher in foals infected with the high inoculum (195+/-145; range 62-328) compared to foals infected with the low inoculum (3.9+/-4.5; range 0.5-11). Similarly, mean (+/-SD) ratio of post-infection to pre-infection IgM concentration was significantly (P=0.002) higher in foals infected with the high inoculum (12+/-4.0; range 7.4-14) compared to foals infected with the low inoculum (2.5+/-1.5; range 1.2-4.7). Proliferative responses to R. equi antigens as well as expression of mRNA for IL-2, IL-4, IL-10, and IFN-gamma in BLN were not significantly different between the two groups. There was a tendency (P=0.073) towards a higher IFN-gamma/IL-4 ratio in the low inoculum group. This study demonstrates that the size of inoculum modulates the IgG subisotype response and possibly the cytokine profile of foals.
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PMID:Effects of inoculum size on cell-mediated and humoral immune responses of foals experimentally infected with Rhodococcus equi: a pilot study. 1972 Apr 2

Epilepsy is a common health problem. Although variety of factors influence the incidence and prevalence of seizures, cytokines are considered to play an important role in seizures. Cytokines are also known to be involved in other neurodegenerative disorders. Proinflammatory cytokines like IL-1, IL-6, TNF-alpha and growth factor vascular endothelial growth factor (VEGF) as well as anti-inflammatory cytokine IL-10 and related molecules have been described in CNS and plasma of experimental models of seizures and clinical cases of epilepsy. There are reports suggesting more predispositions to seizures during inflammatory conditions like colitis, pneumonia and rheumatoid arthritis. These inflammatory cytokines and growth factors are also known to have dual roles in affecting seizure susceptibility. It remains to be seen if cytokine modulators can be therapeutically exploited for patients with inflammatory disorder and suffering from epilepsy.
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PMID:Role of different cytokines and seizure susceptibility: a new dimension towards epilepsy research. 1977 68

The mammalian target of rapamycin (mTOR) is an evolutionary conserved serine-threonine kinase that senses various environmental stimuli in most cells primarily to control cell growth. Restriction of cellular proliferation by mTOR inhibition led to the use of mTOR inhibitors as immunosuppressants in allogeneic transplantation as well as novel anticancer agents. However, distinct inflammatory side effects such as fever, pneumonitis, glomerulonephritis or anemia of chronic disease have been observed under this treatment regime. Apart from the mere cell-cycle regulatory effect of mTOR in dividing cells, recent data revealed a master regulatory role of mTOR in the innate immune system. Hence, inhibition of mTOR promotes proinflammatory cytokines such as IL-12 and IL-1beta, inhibits the anti-inflammatory cytokine IL-10 and boosts MHC antigen presentation via autophagy in monocytes/macrophages and dendritic cells. Moreover, mTOR regulates type I interferon production and the expression of chemokine receptors and costimulatory molecules. These results place mTOR in a complex immunoregulatory context by controlling innate and adaptive immune responses. In this review, we discuss the clinical consequences of mTOR-inhibitor therapy and aim to integrate this recent data into our current view of the molecular mechanisms of clinically employed mTOR inhibitors and discuss their relevance with special emphasis to transplantation.
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PMID:The multifunctional role of mTOR in innate immunity: implications for transplant immunity. 1978

Eleven papers on trauma published in Critical Care during 2008 addressed traumatic brain injury (TBI), burns, diagnostic concerns and immunosuppression. In regard to TBI, preliminary results indicate the utility of either magnetic resonance imaging (MRI) or ultrasound in measuring optic nerve sheath diameter to identify elevated intracranial pressure (ICP) as well as the potential benefit of thiopental for refractory ICP. Another investigation demonstrated that early extubation of TBI patients whose Glasgow Coma Scale score was 8 or less did not result in additional incidence of nosocomial pneumonia. Another study indicated that strict glucose control resulted in worse outcomes during the first week after TBI, but improved outcomes after the second week. Another paper showed the prolonged neuroprotective advantages of progesterone administration in TBI patients. There was also guidance on improved classifications of renal complications in burn patients. Another study found that patients with inhalation injuries and increased interleukin-6 (IL-6) and IL-10 and decreased IL-7 had increased mortality rates. One literature review described the disadvantages of prolonged immobilization or additional use of MRI for ruling out cervical spine injuries in obtunded TBI patients already cleared by computerized tomography scans. Other investigators found that higher N-terminal pro B-type natriuretic peptide (NT-proBNP) levels may be useful markers for post-traumatic cardiac impairment. Finally, an experimental model showed that both splenic apoptosis and lymphocytopenia may occur shortly after severe hemorrhage, thus increasing the threat of immunosuppression in those with severe blood loss.
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PMID:Year in review 2008: Critical Care--trauma. 1986 66

Intense host immune response to infection contributes significantly to the pathology of pneumococcal pneumonia. Therefore, the regulation of host immune response is critical for the successful outcome of pneumonia in such patients. The aim of the present study was to investigate the effect of n-3 PUFA, i.e. flaxseed oil supplementation for short (4 weeks) as well as long (9 weeks) term, on the course of S. pneumoniae D39 serotype 2 infection in mice. The efficacy of flaxseed oil supplementation was investigated in terms of survival of animals and production of various inflammatory molecules (malondialdehyde, myeloperoxidase, nitric oxide) in the lung homogenate of animals. This was correlated with bacteriological and histopathological parameters. The immunomodulation was studied in terms of cytokines in the lungs following infection with Streptococcus pneumoniae. Results suggest that long-term flaxseed supplementation protected the mice against bacterial colonization of lungs with Streptococcus pneumoniae with reduced histopathological involvement of lung tissue. Moderate pneumonia was observed in supplemented, infected mice compared to severe pneumonia seen in control mice. This was accompanied by decreased inflammatory markers (malondialdehyde, myeloperoxidase, nitric oxide) as the disease progressed. In addition, difference in the levels of pro-inflammatory (TNF-alpha and IL-1beta) and anti-inflammatory (IL-10) cytokines was observed in the flaxseed fed animals. On the contrary, short-term supplementation did not show such an effect on lung colonization.
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PMID:Long-term flaxseed oil supplementation diet protects BALB/c mice against Streptococcus pneumoniae infection. 1992 Dec 54

Whereas pneumonia is the most common cause of death and disability worldwide, most cases of pneumonia spontaneously resolve. Mechanisms that promote pneumonia resolution remain to be determined. Resolvin E1 (RvE1) is an endogenous mediator that displays proresolving actions in sterile inflammation. In this study, we developed a new model of aspiration pneumonia to evaluate the effect of RvE1 on acute lung injury caused by acid aspiration and subsequent bacterial challenge. Mice received hydrochloric acid into the left lung followed by the enteric pathogen Escherichia coli. I.v. administration of RvE1 (approximately 0.005 mg/kg) prior to acid injury selectively decreased lung neutrophil accumulation by 55% and enhanced clearance of E. coli. RvE1 significantly decreased lung tissue levels of several proinflammatory chemokines and cytokines, including IL-1beta, IL-6, HMGB-1, MIP-1alpha, MIP-1beta, keratinocyte-derived chemokine, and MCP-1, in a manner independent of the anti-inflammatory mediators IL-10 and lipoxin A4. In addition, animals treated with RvE1 had a marked improvement in survival. These findings in experimental aspiration pneumonia have uncovered protective roles for RvE1 in pathogen-mediated inflammation that are both anti-inflammatory for neutrophils and protective for host defense, suggesting that RvE1 represents the first candidate for a novel therapeutic strategy for acute lung injury and pneumonia that harnesses natural resolution mechanisms.
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PMID:The anti-inflammatory and proresolving mediator resolvin E1 protects mice from bacterial pneumonia and acute lung injury. 2000 39

Cigarette smoke exposure increases the risk of pulmonary and invasive infections caused by Streptococcus pneumoniae, the most commonly isolated organism from patients with community-acquired pneumonia. Despite this association, the mechanisms by which cigarette smoke exposure diminishes host defense against S. pneumoniae infections are poorly understood. In this study, we compared the responses of BALB/c mice following an intratracheal challenge with S. pneumoniae after 5 weeks of exposure to room air or cigarette smoke in a whole-body exposure chamber in vivo and the effects of cigarette smoke on alveolar macrophage phagocytosis of S. pneumoniae in vitro. Bacterial burdens in cigarette smoke-exposed mice were increased at 24 and 48 h postinfection, and this was accompanied by a more pronounced clinical appearance of illness, hypothermia, and increased lung homogenate cytokines interleukin-1beta (IL-1beta), IL-6, IL-10, and tumor necrosis factor alpha (TNF-alpha). We also found greater numbers of neutrophils in bronchoalveolar lavage fluid recovered from cigarette smoke-exposed mice following a challenge with heat-killed S. pneumoniae. Interestingly, overnight culture of alveolar macrophages with 1% cigarette smoke extract, a level that did not affect alveolar macrophage viability, reduced complement-mediated phagocytosis of S. pneumoniae, while the ingestion of unopsonized bacteria or IgG-coated microspheres was not affected. This murine model provides robust additional support to the hypothesis that cigarette smoke exposure increases the risk of pneumococcal pneumonia and defines a novel cellular mechanism to help explain this immunosuppressive effect.
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PMID:Cigarette smoke exposure impairs pulmonary bacterial clearance and alveolar macrophage complement-mediated phagocytosis of Streptococcus pneumoniae. 2000 40

Paired immunoglobulin-like type 2 receptors (PILRs) inhibitory PILRalpha and activating PILRbeta are predominantly expressed on myeloid cells. Their functions in host defense and inflammation are largely unknown, and in this study, we evaluated their roles in an acute Staphylococcus aureus pneumonia model. Compared to their respective controls, Pilrb(-/-) mice or mice in which PILRalpha was activated with an agonistic antibody showed improved clearance of pulmonary staphylococci and improved survival. These mice had reduced serum or bronchoalveolar lavage fluid levels of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and IL-6 and elevated levels of gamma interferon (IFN-gamma), IL-12, and IL-10. In contrast, mice in which PILRbeta was activated had increased lung bacterial burdens and higher mortality coupled with an intense proinflammatory response with highly elevated levels of IL-1beta, TNF-alpha, and IL-6. Treatment groups with reduced bacterial burdens had higher levels of Keratinocyte-derived chemokine (KC), macrophage inflammatory protein 2 (MIP-2), and MIP-1alpha in bronchoalveolar lavage fluid and an increased influx of neutrophils and macrophages to the lungs. Consistent with our in vivo findings, bone marrow-derived macrophages from Pilrb(-/-) mice released significantly less IL-1beta and TNF-alpha and more IFN-gamma and IL-12 than did the wild-type macrophages when directly stimulated with heat-killed S. aureus. To our knowledge, this is the first evidence that S. aureus directly interacts with PILRbeta. It provides a mechanism by which manipulating the balance in favor of an inhibitory PILR signal, by activation of PILRalpha or deletion of PILRbeta, helps to control acute S. aureus-mediated pneumonia and attenuate the inflammatory response. These results highlight the importance of PILRs in innate immunity and the control of inflammation.
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PMID:Modulation of paired immunoglobulin-like type 2 receptor signaling alters the host response to Staphylococcus aureus-induced pneumonia. 2006 29

Conventional vaccines to prevent the pneumonia caused by Rhodococcus equi have not been successful. We have recently demonstrated that immunization with Salmonella enterica Typhimurium expressing the VapA antigen protects mice against R. equi infection. We now report that oral vaccination of mice with this recombinant strain results in high and persistent fecal levels of antigen-specific IgA, and specific proliferation of the spleen cells of immunized mice in response to the in vitro stimulation with R. equi antigen. After in vitro stimulation, spleen cells of immunized mice produce high levels of Th1 cytokines and show a prominent mRNA expression of the Th1 transcription factor T-bet, in detriment of the Th2 transcription factor GATA-3. Following R. equi challenge, a high H2O2, NO, IL-12, and IFN-gamma content is detected in the organs of immunized mice. On the other hand, TNF-alpha and IL-4 levels are markedly lower in the organs of vaccinated mice, compared with the non-vaccinated ones. The IL-10 content and the mRNA transcription level of TGF-beta are also higher in the organs of immunized mice. A greater incidence of CD4+ and CD8+ T cells and B lymphocytes is verified in vaccinated mice. However, there is no difference between vaccinated and non-vaccinated mice in terms of the frequency of CD4+CD25+Foxp3+ T cells. Finally, we show that the vaccination confers a long-term protection against R. equi infection. Altogether, these data indicate that the oral vaccination of mice with S. enterica Typhimurium expressing VapA induces specific and long-lasting humoral and cellular responses against the pathogen, which are appropriately regulated and allow tissue integrity after challenge.
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PMID:Vaccination of mice with salmonella expressing VapA: mucosal and systemic Th1 responses provide protection against Rhodococcus equi infection. 2007 23

Effects of the brominated flame retardants (BFRs), decabrominated diphenyl ether (DBDE), hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA), on host immunity of mice were evaluated using respiratory syncytial virus (RSV) infection. Five-week-old female mice were fed a diet containing 1% BFRs for 28days, and subsequently infected with RSV. No toxicological sign was observed in BFR-treated mice before infection. TBBPA significantly increased the pulmonary viral titer in the infected mice on day 5 post-infection, but DBDE and HBCD did not. Slight histological changes were observed in lung tissues of TBBPA-treated mice with mock infection. These changes due to TBBPA were much exacerbated by RSV infection. Cytokine analysis of bronchoalveolar lavage fluid (BALF) from RSV-infected mice treated with or without TBBPA revealed that TBBPA significantly increased the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and interferon (IFN)-gamma at each time point after virus infection, but no change was observed for IL-1beta and IL-12. The levels of IL-4 and IL-10, Th2 cytokines, significantly decreased. Thus, TBBPA caused unusual production of the various cytokines in RSV-infected mice. Flow cytometry revealed that the percentage of double-positive CD4+CD8+ cells, immature T lymphocytes, in the cell populations in BALF from RSV-infected mice increased due to TBBPA treatment. The change was not observed in spleen cells of TBBPA-treated mice. The response to RSV infection verified that TBBPA treatment affected the host immunity of mice. Irregular changes in cytokine production and immune cell populations due to TBBPA treatment were suggested to cause exacerbation of pneumonia in RSV-infected mice.
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PMID:Effects of tetrabromobisphenol A, a brominated flame retardant, on the immune response to respiratory syncytial virus infection in mice. 2007 68


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