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)

A 3-yr-old female patient exhibited interleukin 12 (IL-12) deficiency that was associated with recurrent episodes of pneumococcal pneumonia with sepsis and other infections in the absence of fevers. The patient's peripheral blood mononuclear cells (PBMCs) exhibited normal proliferative responses to antigens. Immune responses, including in vivo production of antibodies to diphtheria, tetanus, or pneumococcal antigens, were normal. Ig levels and B cell and T cell phenotypes were also normal. In contrast, IL-12 p70 heterodimer production was undetectable by using supernatants of the patient's stimulated PBMCs when compared with control cells treated similarly. Although present, interferon gamma (IFN-gamma) was reduced. The addition of recombinant IFN-gamma to control cells enhanced the production of IL-12 by up to sixfold. By contrast, IL-12 was undetectable in supernatants of the patient's cells in the presence of recombinant IFN-gamma. IL-12 p40 subunit mRNA by using the patient's PBMCs after stimulation with Staphylococcus aureus Cowan strain 1 or lipopolysaccharide was also undetectable by reverse transcription-PCR when compared with control cells. Production of IL-2, IL-6, tumor necrosis factor alpha, or IFN-gamma of the patient's PBMCs after appropriate stimulation was observed. This patient has either a defect in Staphylococcus aureus Cowan strain 1-lipopolysaccharide- or staphylococcal enterotoxin A-induced signaling pathways for the activation of IL-12 p40 gene expression, or an abnormality in the IL-12 p40 gene itself.
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PMID:Interleukin 12 deficiency associated with recurrent infections. 978 52

Pseudomonas aeruginosa, an opportunistic human pathogen, causes acute pneumonia in patients with hospital-acquired infections and is commonly associated with chronic lung disease in individuals with cystic fibrosis (CF). Evidence suggests that the pathophysiological effects of P. aeruginosa are mediated in part by virulence factors secreted by the bacterium. Among these factors is pyocyanin, a redox active compound that increases intracellular oxidant stress. We find that pyocyanin increases release of interleukin-8 (IL-8) by both normal and CF airway epithelial cell lines and by primary airway epithelial cells. Moreover, pyocyanin synergizes with the inflammatory cytokines tumor necrosis factor alpha and IL-1alpha. RNase protection assays indicate that increased IL-8 release is accompanied by increased levels of IL-8 mRNA. The antioxidant n-acetyl cysteine, general inhibitors of protein tyrosine kinases, and specific inhibitors of mitogen-activated protein kinases diminish pyocyanin-dependent increases in IL-8 release. Conversely, inhibitors of protein kinases C (PKC) and PKA have no effect. In contrast to its effects on IL-8 expression, pyocyanin inhibits cytokine-dependent expression of the monocyte/macrophage/T-cell chemokine RANTES. Increased release of IL-8, a potent neutrophil chemoattractant, in response to pyocyanin could contribute to the marked infiltration of neutrophils and subsequent neutrophil-mediated tissue damage that are observed in Pseudomonas-associated lung disease.
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PMID:Pseudomonas pyocyanin increases interleukin-8 expression by human airway epithelial cells. 982 54

The molecular mechanisms of resistance to genital infection with the mouse pneumonitis (MoPn) strain of Chlamydia trachomatis are unknown. A role for major histocompatibility complex class II-restricted, interleukin-12-dependent CD4(+) T cells has been established, but the functional activity of these cells does not depend on secretion of gamma interferon. Here we examined the potential contribution of T-cell-mediated cytotoxicity and apoptosis to mucosal clearance of MoPn by using mice deficient in the molecular mediators of target cell lysis. Animals lacking perforin, Fas, Fas ligand, or both perforin and Fas ligand were infected genitally with C. trachomatis MoPn and monitored for expression of immunity to chlamydial antigens and clearance of MoPn from the genital mucosa. In each case, the profile of spleen cytokine production, the magnitude of the host antibody response, and the kinetics of chlamydial clearance were similar to those of genetically intact controls. Compensatory overproduction of tumor necrosis factor alpha, an alternate mediator of apoptosis in certain cell types, did not appear to account for the ability of mutant mice to resolve Chlamydia infections. These results fail to support CD4(+) T-cell-mediated apoptosis or CD8(+) T-cell-mediated cytotoxicity as being critical to the clearance of C. trachomatis MoPn urogenital infections.
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PMID:Clearance of Chlamydia trachomatis from the murine genital mucosa does not require perforin-mediated cytolysis or Fas-mediated apoptosis. 1002 85

Weight loss in elderly patients is a common clinical problem. Wasting and cachexia are associated with severe physiologic, psychologic, and immunologic consequences, regardless of the underlying causes. Cachexia has been associated with infections, decubitus ulcers, and even death. Multivariate analyses of risk and prognostic factors in community-acquired pneumonia in the elderly have found that age by itself is not a significant factor related to prognosis. Among the significant risk factors, only nutritional status is amenable to medical intervention. Cachexia in the elderly may have profound consequences: medical, cognitive, and psychiatric disorders may diminish self-reliance in activities of daily living, thus reducing quality of life and increasing the frequency of secondary procedures, hospitalizations, and the need for skilled care. Cachexia is associated with higher-than-normal concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 1, IL-6, serotonin, and interferon gamma. The role of these proinflammatory cytokines has been established in the cachexia seen in cancer and AIDS patients. Reduction in the concentrations of these cytokines is associated with weight gain. Drugs that promote appetite stimulation and weight gain, such as progestational agents, cyproheptadines, pentoxifylline, and thalidomide may work by down-regulating these proinflammatory cytokines. An understanding of the relation between cachexia and negative regulatory cytokines may point to effective treatment of geriatric cachexia as well.
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PMID:Geriatric cachexia: the role of cytokines. 1070 92

It has recently become apparent that inflammatory reactions including nitric oxide (NO) release contribute to the outcome of pulmonary infections. To investigate the effect of N(G)-monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor, on the pathogenesis of pneumococcal pneumonia, we inoculated CD(1) Swiss mice with 10(7) CFU of Streptococcus pneumoniae. Treatment with two daily subcutaneous injections of 3 mg of L-NMMA per kg of body weight (over a 5-day period) reproducibly delayed mortality, as the number of surviving mice 72, 84, and 96 h after infection was increased by 16.8% (P < 0.05), 25.0% (P < 0.005), and 11.5% (P < 0. 05), respectively. In fact, the following chronology of events was noted in L-NMMA-treated infected animals, compared to the untreated infected controls. (i) At 12 to 24 h after infection, larger amounts of leukotriene B(4) in bronchoalveolar lavage (BAL) fluid associated with greater neutrophilia in lung tissue and alveolar spaces and more persistent release of tumor necrosis factor alpha, interleukin-1 alpha (IL-1alpha), and IL-6 were observed. (ii) At 24 to 72 h, there was better preservation of lung ultrastructure, including reduction of edema in the interstitium and protection of alveolar spaces, despite identical bacterial growth in lungs, in L-NMMA-treated infected animals than in untreated animals. (iii) At 72 to 96 h, the death rate was delayed, despite the absence of antibiotic therapy. In our experiment, partial blockade of NO release was achieved. These data indicate that NO plays an important role in the induction of tissue injury and death during pneumococcal pneumonia and that L-NMMA is helpful for host protection.
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PMID:Immunomodulation of pneumococcal pulmonary infection with N(G)-monomethyl-L-arginine. 1047 80

Encapsulated Klebsiella pneumoniae strains frequently induce fatal nosocomial pneumonia. Cefodizime (CEF) as an antibiotic is suspected to enhance host resistance against various microbial invasions through interactions with bacteria and host cells. To investigate the influence of CEF on the pulmonary response to Klebsiella that does not merely result from direct bacterial clearance by the drug, we inoculated mice with heat-killed fluorescein isothiocyanate-labeled K. pneumoniae. CEF upregulated (P < 0.01) the early Klebsiella-induced secretion of tumor necrosis factor alpha, as well as the number (P < 0.01) and phagocytic efficacy (P < 0.001) of alveolar macrophages. By contrast, the late polymorphonuclear neutrophil recruitment (P < 0.05) and levels of interleukin-1 alpha (IL-1alpha) (P < 0.05) and IL-6 (P < 0.05) were reduced. The stimulation of an early immune response by CEF followed by late reduction in inflammation may be beneficial against bacterial pneumonia.
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PMID:Influence of cefodizime on pulmonary inflammatory response to heat-killed Klebsiella pneumoniae in mice. 1047 81

The ability of Rhodococcus equi to induce pneumonia in foals depends on the presence of an 85- to 90-kb plasmid. In this study, we evaluated whether plasmid-encoded products mediate virulence by modulating the cytokine response of foals. Foals infected intrabronchially with a virulence plasmid-containing strain of R. equi had similar gamma interferon (IFN-gamma) and interleukin-12 (IL-12) p35 but significantly higher IL-1beta, IL-10, IL-12 p40, and tumor necrosis factor alpha (TNF-alpha) mRNA expression in lung tissue compared to foals infected with the plasmid-cured derivative. IFN-gamma mRNA expression levels in CD4+ T lymphocytes isolated from bronchial lymph nodes (BLN) were similar for the two groups of R. equi-infected foals on day 3 postinfection. However, on day 14, in association with pneumonia and marked multiplication of virulent R. equi but with complete clearance of the plasmid-cured derivative, IFN-gamma mRNA expression in BLN CD4+ T lymphocytes was significantly (P < 0.001) higher in foals infected with the plasmid-cured derivative. These results suggests an immunomodulating role for R. equi virulence plasmid-encoded products in downregulating IFN-gamma mRNA expression by CD4+ T lymphocytes.
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PMID:Modulation of cytokine response of pneumonic foals by virulent Rhodococcus equi. 1049 76

Group B streptococci (GBS) are a major cause of severe infection in newborns, pregnant females, and other immunocompromised hosts. Infection often includes septicemia, shock, pneumonia, and respiratory failure. In previous studies, we have reported that GBS induce marked production of tumor necrosis factor alpha (TNF-alpha) by human mononuclear cells. The present study was designed to measure the production of TNF-alpha as well as additional cytokines, including interleukin 1beta (IL-1beta), IL-6, IL-8, IL-12, and gamma interferon (IFN-gamma) but also to determine from what cells and at what time point during incubation with GBS that these cytokines are produced. Mixed mononuclear cells were incubated with heat-killed GBS, media alone, or 1 microg of Escherichia coli lipopolysaccharide (LPS). Brefeldin A was added to each sample prior to staining, which prevented the export of cytokines by the Golgi apparatus. The cells were then stained with the appropriate conjugated antibodies and analyzed by using a flow cytometer. Results indicate that intracellular cytokines appear, in almost all cases, simultaneous to or before secreted proteins are detected. In contrast to the response to LPS, where TNF-alpha, IL-1beta, IL-6, and IL-8 appear almost simultaneously, the human monocyte response to GBS results in the production of TNF-alpha but delayed appearance of IL-1beta, IL-6, and IL-8. The lymphocyte response to GBS was also strikingly different from that to LPS in that both secreted IFN-gamma and IL-12 was detected, while LPS failed to induce production of these critical cytokines. This suggests an important role for TNF-alpha, IFN-gamma, and IL-12 in GBS pathogenesis and/or immunity.
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PMID:Intracellular and extracellular cytokine production by human mixed mononuclear cells in response to group B streptococci. 1060 4

Adaptive immune responses contribute to the resolution of Chlamydia trachomatis genital tract infection and protect against reinfection, but our understanding of the mechanisms of those protective responses is incomplete. In this study, we analyzed by in situ immunohistochemistry the progression of the inflammatory and cytokine responses in the genital tracts of mice vaginally infected with C. trachomatis strain mouse pneumonitis. The cellular inflammatory response was characterized by an initial elevation in myeloid cells in the vagina (day 3) and uterine horns (day 7), followed by a marked rise in the number of T cells, predominantly CD4(+) cells. CD8(+) T cells and CD45R(+) B cells were also detected but were much less numerous. Perivascular clusters of CD4(+) T cells, which resembled clusters of T cells seen in delayed-type hypersensitivity responses, were evident by 2 weeks postinfection. Following the resolution of infection, few CD8(+) T cells and CD45R(+) B cells remained, whereas numerous CD4(+) T cells and perivascular clusters of CD4(+) T cells persisted in genital tract tissues. Interleukin-12 (IL-12)- and tumor necrosis factor alpha (TNF-alpha)-producing cells were observed in vaginal tissue by day 3 of infection and in uterine tissues by day 7. Cells producing IL-4 or IL-10 were absent from vaginal tissues at day 3 of infection but were present in uterine tissues by day 7 and were consistently more numerous than IL-12- and TNF-alpha-producing cells. Thus, the evolution of the local inflammatory response was characterized by the accumulation of CD4(+) T cells into perivascular clusters and the presence of cells secreting both Th1- and Th2-type cytokines. The persistence of CD4(+)-T-cell clusters long after infection had resolved (day 70) may provide for a readily mobilizable T-cell response by which previously infected animals can quickly respond to and control a secondary infectious challenge.
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PMID:In situ analysis of the evolution of the primary immune response in murine Chlamydia trachomatis genital tract infection. 1120 23

The role of tumor necrosis factor alpha (TNF-alpha) in host defense against chlamydial infection remains unclear. In order to further evaluate the relevance of TNF-alpha to host resistance in chlamydial genital tract infection, we examined the effect of local inhibition of the TNF-alpha response in normal C57 mice and in interferon gamma gene-deficient C57 mice infected intravaginally with the mouse pneumonitis agent of Chlamydia trachomatis. Since the guinea pig model of female genital tract infection more closely approximates the human in terms of ascending infection and development of pathology, we also examined the effect of local inhibition of the TNF-alpha response in guinea pigs infected intravaginally with the guinea pig strain of Chlamydia psittaci. We successfully blocked the early TNF-alpha response in the respective animal models. This blockade had no effect on the numbers of organisms isolated from the genital tract during the time of TNF-alpha inhibition in mice or guinea pigs. Analysis of interleukin-1beta, macrophage inflammatory protein-2, and granulocyte macrophage-colony stimulating factor in the mouse model revealed that blockade of the TNF-alpha response did not alter the release of these proinflammatory proteins. Yet, in TNF-alpha-depleted mice, increased numbers of neutrophils were detected in the genital tract, and, in TNF-alpha-depleted guinea pigs, increased numbers of neutrophils as well as infiltrating lymphocytes were seen in the endocervix. Blockade of TNF-alpha does not affect the level of infection in mice or guinea pigs, but it may decrease TNF-alpha-induced apoptosis of infiltrating inflammatory cells.
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PMID:Does inhibition of tumor necrosis factor alpha affect chlamydial genital tract infection in mice and guinea pigs? 1094 58


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