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)

Serum interleukin 15 (IL-15) levels were measured in 77 patients who were consecutively admitted to our intensive care unit. Postoperative enterocolitis occurred in four patients and Methicillin-resistant Staphylococcus aureus (MRSA), but not Clostridium difficile, was identified in the faecal specimens from these patients. The IL-15 levels in the patients with MRSA enterocolitis were significantly elevated compared with those of other MRSA infections without enterocolitis including pneumonia (n=6) and cholangitis (n=1), and other MRSA non-colonized patients (n=66) (21.2+/-5.2 pg/ml vs 4.3+/-0.2, 4.3+/-0.5). Notably, an increase in serum IL-15 was observed just before clinical manifestation of severe diarrhoea. Our findings suggest that IL-15 may be associated in the pathogenesis of postoperative enterocolitis and its serum level may be a severity indicator of the disease.
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PMID:IL-15 is elevated in the patients of postoperative enterocolitis. 1054 78

IL-15 shares several biological activities with IL-2 and uses the b and g chain of the IL-2 receptor. In addition to its T-cell stimulating capacity, IL-15 exhibits regulatory properties on macrophage proinflammatory cytokine release. IL-15 is released by non-lymphoid cells, e.g. muscle cells, fibroblasts and monocytes/macrophages. In many lung diseases alveolar macrophages (AM) are activated and release pro- inflammatory cytokines. We asked whether IL-15 is released ex vivo by AM and peripheral blood mononuclear cells (PBMC) from patients with inactive sarcoidosis (PSi), active sarcoidosis (PSa), tuberculosis (TB), hypersensitivity pneumonitis (HSP), cryptogenic fibrosing alveolitis (CFA) and pneumonia (PN). Additionally, we examined the kinetics of the IL-15 release of these cells. During 24 hours of culture, AM from controls (CO) released 3.8 +/- 1.9 pg/ml (mean +/- SD) of IL-15, which was significantly lower than in most of the patient groups (PSa: 8.7 +/- 3.9 pg/ml, TB: 8.4 +/- 1.9 pg/ml, CFA: 5.7 +/- 1.5 pg/ml, and PN: 7. 8 +/- 2.6 pg/ml) except PSi (4.0 +/- 2.6 pg/ml) and HSP (9.3 +/- 9.5 pg/ml). PBMC from patients with PSa released significantly more IL-15 than PBMC from CO (10.8 +/- 8.9 pg/ml versus 6.9 +/- 2.2 pg/ml) whereas PBMC IL-15 release of the other groups did not differ from CO (TB: 5.7 +/- 1.4 pg/ml; CFA: 4.6 +/- 1.6 pg/ml; HSP: 4.9 +/- 3.8 pg/ml). Kinetic studies revealed a minor peak after 5 hours and a major peak from 12 hours to 35 hours for AM and PBMC. In summary, AM from all patient groups but the PSi and the HSP group released increased levels of IL-15, although the total amount of this cytokine is very low.
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PMID:In vitro release of interleukin-15 by broncho-alveolar lavage cells and peripheral blood mononuclear cells from patients with different lung diseases. 1070 7

The corticosteroid-treated animal is well established as an experimental model for the study of Pneumocystis carinii pneumonitis (PCP). Latent or acquired infection with P. carinii in the murine lung progresses to fatal pneumonitis when the host is profoundly immunocompromized. In this study the effects of five immunomodulators; recombinant CD40 ligand (CD40L), bryostatin 1, recombinant FLT3 ligand (FLT3L), recombinant granulocyte colony-stimulating factor (G-CSF) and recombinant interleukin-15 (IL-15) were investigated against PCP in a dexamethasone immunosuppressed Sprague-Dawley rat model. The majority of rats (70%) treated with CD40L at the onset of dexamethasone immunosuppression were protected against PCP. When CD40L was given after 10 days of immunosuppression, only 40% of the rats resolved the infection. However, 95% of the control animals developed PCP. Immunosuppressed rats treated with bryostatin 1, an immune activator had a partial (50%) protection against P. carinii infection. In contrast, daily administration of FLT3L, IL-15 or G-CSF provided no protection against P. carinii infection.
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PMID:Effect of CD40 ligand and other immunomodulators on Pneumocystis carinii infection in rat model. 1096 50

Suppressor of cytokine signaling-1 (SOCS-1) is an essential regulator of cytokine signaling. SOCS-1-/- mice die before weaning with a complex disease characterized by fatty degeneration and necrosis of the liver. This disease is mediated by interferon (IFN) gamma as neonatal mortality fails to occur in SOCS-1-/-IFNgamma-/- mice. However, the immune system of healthy SOCS-1-/-IFNgamma-/- mice is dysregulated with a reduced ratio of CD4:CD8 T cells and increases in some aspects of T cell activation. SOCS-1-/-IFNgamma-/- mice also die before their wild type and IFNgamma-/- counterparts with a range of inflammatory conditions including pneumonia, gut infiltration, and skin ulceration, suggesting that SOCS-1 controls not only IFNgamma signaling, but also other immunoregulatory factors. This study shows that T cells from SOCS-1-deficient mice display hypersensitivity to cytokines that act through the gammac receptor. SOCS-1 expression is induced by interleukin (IL) 2, IL-4, IL-7, and IL-15, and SOCS-1-deficient T cells show increased proliferation and prolonged survival in response to IL-2 and IL-4. Furthermore, IL-2 induced increased STAT5 phosphorylation and CD44 expression in SOCS-1-deficient T cells compared with controls. Hypersensitivity to gammac-dependent cytokines may contribute to abnormal T cell function, as well as the pathology observed in mice lacking SOCS-1.
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PMID:Suppressor of cytokine signaling-1 regulates signaling in response to interleukin-2 and other gamma c-dependent cytokines in peripheral T cells. 1266 16

Patients with large burn injuries are susceptible to opportunistic infections due to impaired functions of multiple effector cells of innate immunity and acquired immunity, including macrophages, dendritic cells (DC), natural killer (NK) cells, and T cells. The ability of a host to produce Th1 cytokines, such as gamma interferon (IFN-gamma) and interleukin-12 (IL-12), upon infectious challenge is also impaired after burn injury. Stimulation of hematopoiesis, to regenerate new immune cells, may be an effective strategy for improving resistance to infections after severe burn trauma. Fms-like tyrosine kinase 3 ligand (Flt3L) is a hematopoietic cytokine that stimulates the expansion and differentiation of NK cells and DC. Using a mouse model, we tested the hypothesis that Flt3L treatments after burn injury stimulate the production of functional effector cells of innate immunity and restore appropriate Th1 cytokine responses to Pseudomonas aeruginosa, a common source of pneumonia and wound infections in burn victims. Flt3L increased splenic cellularity in sham (uninjured) and burned mice and increased the numbers of NK cells (DX5(+)) and DC (CD11c(+)). In response to P. aeruginosa, significant increases in the serum IFN-gamma levels and the numbers of splenic IFN-gamma-producing DC, NK cells, and T cells were observed in Flt3L-treated burned mice compared to the values obtained for untreated burned mice. The splenic levels of IL-12 and IL-15 mRNAs and the IL-12 and IL-15 receptors were also increased. In addition, Flt3L treatment restored the ability of splenic cultures prepared from burned mice to produce IFN-gamma and IL-12 after in vitro challenge with P. aeruginosa. Flt3L may have potential for restoring NK cell and DC functions and improving immunity after burn injury.
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PMID:Stimulation of hematopoiesis by the Fms-like tyrosine kinase 3 ligand restores bacterial induction of Th1 cytokines in thermally injured mice. 1276 Oct 83

Loss of T cell number and function during HIV infection or secondary to pharmacologic immunosuppression renders individuals susceptible to opportunistic infections, including Pneumocystis carinii pneumonia. Because costimulatory receptors are critical for optimal T cell function, we hypothesized that these proteins would regulate susceptibility to opportunistic infections. We found that despite normal T cell numbers, mice deficient in the costimulatory molecules CD2 and CD28 spontaneously developed P. carinii pneumonia. In experiments using intratracheal injection of P. carinii organisms to induce infection, the loss of CD28 alone was sufficient to render mice susceptible to acute infection; however, the organism was eventually cleared. Examination of inflammatory responses to P. carinii revealed that mice deficient in both CD2 and CD28 accumulated CD8(+) T cells in their lungs in response to infection and demonstrated markedly reduced specific Ab titers. Analysis of cytokine profiles suggested that regulation of IL-10 and IL-15 may be important elements of the response to this pathogen. Thus, costimulatory molecule function is critical in determining the initial susceptibility to infection with P. carinii. Analysis of immunologic responses in these mice may provide important insights into the defects that render individuals susceptible to opportunistic infection, and provide opportunities for novel immunologically based therapies.
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PMID:T cell costimulatory molecule function determines susceptibility to infection with Pneumocystis carinii in mice. 1290

Interleukin (IL)-15 has critical impact on the homeostasis and activation of natural killer cells, natural killer T cells, gammadeltaT cells, and CD8(+)T cells, and contributes to antimicrobial defenses particularly at mucosal sites. The respiratory tract comprises a large mucosal surface and harbors significant amounts of lymphocytes, however the expression pattern of IL-15 in the lung and its role in local immune responses are largely unknown. We therefore analyzed the differential expression of IL-15 and the IL-15 receptor (IL-15R) complex in the lungs of mice and demonstrated substantial constitutive expression in bronchial and alveolar epithelial cells, alveolar macrophages, and vascular smooth muscle cells, implicating contribution to pulmonary immune cell homeostasis already under normal conditions. The induction of pneumococcal pneumonia but not the infection with Chlamydophila pneumoniae evoked a significant up-regulation of IL-15 on alveolar macrophages and bronchial epithelial cells, with the latter presenting de-novo expression of IL-15 on their basolateral surface and additional up-regulation of IL-15Ralpha. Moreover, transcriptome analysis as well as semi-quantitative PCR indicated at least partial transcriptional regulation in mice lungs. In conclusion IL-15 is suggested being of functional importance in the pulmonary immune response against pneumococcal pneumonia.
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PMID:Cell-specific interleukin-15 and interleukin-15 receptor subunit expression and regulation in pneumococcal pneumonia--comparison to chlamydial lung infection. 1761 Nov 21

Polymorphonuclear leukocytes (PMNs) can be divided into Gr-1(high) and Gr-1(low) subpopulations, but the differences in the functions of these cells in the host are unknown. This study investigated the roles of these two cell populations in the clearance of an intracellular pathogen (Haemophilus influenzae) causing murine peritonitis and pneumonia. Microarray analysis and quantitative real-time PCR analysis of proteose peptone-elicited peritoneal murine PMNs showed that IL-15 mRNA levels were significantly higher in Gr-1(high) PMNs than in Gr-1(low) PMNs. In addition, IL-15 was produced only by Gr-1-positive PMNs, especially Gr-1(high) PMNs. IL-15 was required for efficient clearance of experimental murine H. influenzae pneumonia, as 4 days postinfection lungs from IL-15 knockout mice contained 50- to 100-fold more bacteria than did wild-type mouse lungs. Gr-1 PMN-depleted C57BL/6 mice were more susceptible to H. influenzae pneumonia than were Gr-1 PMN replete C57BL/6 mice or C57BL/6 nude mice, demonstrating that Gr-1 PMNs are important in the clearance of intracellular bacteria. IL-15-activated NK cells killed H. influenzae in PMNs. Flow cytometry confirmed the expression of CD69 on the cell membrane of IL-15-activated NK cells. Our results show that Gr-1(high) PMNs produce more IL-15 than Gr-1(low) PMNs, and that IL-15-activated NK cells protect against early infection by H. influenzae.
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PMID:Gr-1high polymorphonuclear leukocytes and NK cells act via IL-15 to clear intracellular Haemophilus influenzae in experimental murine peritonitis and pneumonia. 1791 27

IL-15 is a pluripotent antiapoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy. Sepsis is a lethal condition in which apoptosis-induced depletion of immune cells and subsequent immunosuppression are thought to contribute to morbidity and mortality. This study tested the ability of IL-15 to block apoptosis, prevent immunosuppression, and improve survival in sepsis. Mice were made septic using cecal ligation and puncture or Pseudomonas aeruginosa pneumonia. The experiments comprised a 2 x 2 full factorial design with surgical sepsis versus sham and IL-15 versus vehicle. In addition to survival studies, splenic cellularity, canonical markers of activation and proliferation, intracellular pro- and antiapoptotic Bcl-2 family protein expression, and markers of immune cell apoptosis were evaluated by flow cytometry. Cytokine production was examined both in plasma of treated mice and splenocytes that were stimulated ex vivo. IL-15 blocked sepsis-induced apoptosis of NK cells, dendritic cells, and CD8 T cells. IL-15 also decreased sepsis-induced gut epithelial apoptosis. IL-15 therapy increased the abundance of antiapoptotic Bcl-2 while decreasing proapoptotic Bim and PUMA. IL-15 increased both circulating IFN-gamma, as well as the percentage of NK cells that produced IFN-gamma. Finally, IL-15 increased survival in both cecal ligation and puncture and P. aeruginosa pneumonia. In conclusion, IL-15 prevents two immunopathologic hallmarks of sepsis, namely, apoptosis and immunosuppression, and improves survival in two different models of sepsis. IL-15 represents a potentially novel therapy of this highly lethal disorder.
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PMID:IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis. 2060 9

Highly pathogenic influenza A viruses cause acute severe pneumonia to which the occurrence of "cytokine storm" has been proposed to contribute. Here we show that interleukin-15 (IL-15) knockout (KO) mice exhibited reduced mortality after infection with influenza virus A/FM/1/47 (H1N1, a mouse-adapted strain) albeit the viral titers of these mice showed no difference from those of control mice. There were significantly fewer antigen-specific CD44(+) CD8(+) T cells in the lungs of infected IL-15 KO mice, and adoptive transfer of the CD8(+) T cells caused reduced survival of IL-15 KO mice following influenza virus infection. Mice deficient in beta(2)-microglobulin by gene targeting and those depleted of CD8(+) T cells by in vivo administration of anti-CD8 monoclonal antibody displayed a reduced mortality rate after infection. These results indicate that IL-15-dependent CD8(+) T cells are at least partly responsible for the pathogenesis of acute pneumonia caused by influenza A virus.
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PMID:Interleukin-15 is critical in the pathogenesis of influenza a virus-induced acute lung injury. 2033 67


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