Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bronchiolitis obliterans (BO), a common complication in lung transplant recipients, is a fibrotic process probably related to acute rejection (AR) and cytomegalovirus pneumonitis (CMVP). Because the pathogenesis of pulmonary fibrotic diseases involves activation of alveolar macrophages (AM), the present study was carried out to determine if AM were activated during AR, CMVP, and BO. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured in 157 AM supernatants obtained from 29 transplant recipients by immunoradiometric assay. Five groups were analyzed: AR (n = 21), CMVP (n = 12), BO (n = 15), bacterial pneumonia (BP) (n = 8), and control subjects (n = 70). Cytokines were also assayed 15 d (n = 15) and 30 d (n = 9) after AR and 30 d (n = 9) after CMVP. Cytokine secretion was elevated during AR (TNF-alpha = 3,709 +/- 1,409 pg/10(6) cells, IL-6 = 5,482 +/- 2,058 pg/10(6) cells, p < 0.005), and they returned to control values within 15 d. A similar pattern was observed during CMVP (TNF-alpha = 5,000 +/- 2,773 pg/10(6) cells, IL-6 = 12,280 +/- 3,939 pg/10(6) cells, p < 0.005), and values returned to control levels within 30 d. During BP, cytokine production values were higher than control values, but to a lesser extent than in AR and CMVP (TNF-alpha = 2,502 +/- 1,072, p < 0.05; IL-6 = 3,734 +/- 1,440, p < 0.005). In contrast, cytokine secretion during BO was not statistically different from that of control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monitoring of alveolar macrophage production of tumor necrosis factor-alpha and interleukin-6 in lung transplant recipients. Marseille and Montreal Lung Transplantation Group. 808 38

Chronic ethanol ingestion predisposes to tuberculosis and bacterial pneumonia. Mycobacterium avium complex organisms cause bacteremia in patients with AIDS. Human macrophages and murine Kupffer cells exposed to ethanol are more permissive towards intracellular growth of M. avium than control mononuclear phagocytes. Ethanol also has been shown to impair the ability of human macrophages and murine Kupffer cells to respond to stimulation with tumor necrosis factor (TNF) and granulocyte macrophage colony stimulating factor (GM-CSF), and to produce cytokines such as interleukin-1, interleukin-6, and TNF when properly stimulated. The impairment is dependent in part on a downregulation in the number of TNF receptors on the macrophage's membrane. Recent evidence suggests that ethanol in nonlethal concentrations induces stress-related proteins in M. avium, leading to the inhibition of intracellular pathways in the macrophage and, consequently, impairing some of its functions. In summary, ethanol acts both on the host and on the mycobacterium in a complex sequence of events that influence the outcome of the infection.
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PMID:Effect of ethanol on the interaction between the macrophage and Mycobacterium avium. 820 5

C-reactive protein (CRP) in the patients with eosinophilic pneumonia was examined compared with that of bacterial pneumonia. While no difference between erythrocyte sedimentation rate (ESR) in eosinophilic pneumonia (mean +/- SE: 74.5 +/- 10.6 mm/hr) and that in bacterial pneumonia (86.2 + 7.7 mm/hr) was observed, serum CRP level (3.87 +/- 1.24 mg/dL) and alpha 2-macroglobulin level (182.53 +/- 13.00 mg/dL) in eosinophilic pneumonia were lower in comparison with those in bacterial pneumonia (14.89 +/- 1.34 mg/dL, 315.65 +/- 11.54 mg/dL, respectively), suggesting that the pathogenesis of eosinophilic pneumonia might involve defective secretion of certain cytokine related to the production of acute-phase reactant proteins such as interleukin-6.
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PMID:Possible low response of C-reactive protein production in eosinophilic pneumonia. 873 34

We investigated the influence of HMR 3004, a new ketolide antibiotic, on the pulmonary inflammation induced by heat-killed fluorescein isothiocyanate-labeled Streptococcus pneumoniae. HMR 3004 downregulated (P < 0.05) the pneumococcus-induced release of interleukin-6 (IL-6), IL-1beta, and nitric oxide in bronchoalveolar lavage fluid. The drug limited (P < 0.05) neutrophil recruitment to lung tissues and alveoli but did not interfere with phagocytosis. HMR 3004 totally abrogated lung edema. By reducing inflammation in addition to possessing antimicrobial properties, HMR 3004 may participate in improving the outcome of bacterial pneumonia.
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PMID:Immunomodulating effects of HMR 3004 on pulmonary inflammation caused by heat-killed Streptococcus pneumoniae in mice. 983 35

Pneumonia is a common cause of hospitalization and is associated with high morbidity in children. Tumor necrosis factor-alpha (TNF-alpha) and Interleukin-6 (IL-6) are primary mediators of inflammation, and have been implicated in a large number of infectious and non-infectious inflammatory diseases. The serum concentrations of TNF-alpha and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) in 27 patients with bacterial pneumonia (n = 12) or respiratory syncytial virus (RSV) pneumonia (n = 15) and in 15 healthy control subjects. TNF-alpha concentrations of patients with bacterial pneumonia in acute stage (16.94 +/- 5.70 ng/L) were significantly higher than those in convalescent stage (5.80 +/- 0.75 ng/L), in patients with RSV pneumonia (5.06 +/- 0.44 ng/L) and in healthy control subjects (5.39 +/- 0.68 ng/L) (p < 0.005). TNF-alpha concentrations of patients with RSV pneumonia were not significantly different from those of the control group. IL-6 concentrations of patients with bacterial pneumonia in acute stage (465.94 +/- 290.30 ng/L) were significantly higher than those in convalescent stage (22.04 +/- 15.08 ng/L), in patients with RSV pneumonia (7.65 +/- 2.58 ng/L), and in healthy control subjects (0.84 +/- 0.08 ng/L) (p < 0.0005). There was significant difference between patients with RSV pneumonia and the healthy control group (p < 0.005). In summary, there were significant differences in TNF-alpha and IL-6 concentrations between acute stage and convalescent stage in patients with bacterial pneumonia, making them useful as markers for bacterial pneumonia. Further studies are needed to establish the potential diagnostic and prognostic value of TNF-alpha and IL-6.
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PMID:Tumor necrosis factor-alpha and interleukin-6 profiles in children with pneumonia. 1065 Apr 87

Patients still die from Streptococcus pneumoniae pneumonia after initiation of antibiotic therapy, when tissues are sterile and the pneumonia is clearing. There is growing evidence that overwhelming inflammation resulting from toxin release contributes to tissue injury, shock, and death. Monitoring host response may help us understand the consequences of antibiotic therapy for the inflammatory processes that occur in bacterial pneumonia. HMR 3004 is a ketolide that displays excellent in vitro activity against S. pneumoniae. In the present experiment, we investigated the chronology of inflammatory events that occur during pneumococcal pneumonia in mice treated with HMR 3004. Infection of mice with 10(7) CFU of living S. pneumoniae resulted in 100% mortality within 5 days. HMR 3004 given at 12.5 mg/kg of body weight/dose twice daily from 48 h postinfection achieved complete bacterial clearance from lungs and blood within 36 h and ensured survival of mice. Recruitment of neutrophils and monocytes from blood to lungs was significantly reduced, and nitric oxide release was totally prevented. Interleukin-6 secretion in lungs and blood became rapidly undetectable after initiation of therapy. Histological examination of lung tissue showed protection of interstitium against edema. By controlling bacterial invasion, HMR 3004 led to rapid and profound modifications of the host response in lungs, which may protect mice from deleterious inflammatory reactions.
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PMID:Kinetic study of the inflammatory response in Streptococcus pneumoniae experimental pneumonia treated with the ketolide HMR 3004. 1112 Sep 74

Eighteen cases of human influenza A H5N1 infection were identified in Hong Kong from May to December 1997. Two of the six fatal cases had undergone a full post-mortem which showed reactive hemophagocytic syndrome as the most prominent feature. Other findings included organizing diffuse alveolar damage with interstitial fibrosis, extensive hepatic central lobular necrosis, acute renal tubular necrosis and lymphoid depletion. Elevation of soluble interleukin-2 receptor, interleukin-6 and interferon-gamma was demonstrated in both patients, whereas secondary bacterial pneumonia was not observed. Virus detection using isolation, reverse transcription-polymerase chain reaction and immunostaining were all negative. It is postulated that in fatal human infections with this avian subtype, initial virus replication in the respiratory tract triggers hypercytokinemia complicated by the reactive hemophagocytic syndrome. These findings suggest that the pathogenesis of influenza A H5N1 infection might be different from that of the usual human subtypes H1-H3.
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PMID:Pathology of fatal human infection associated with avian influenza A H5N1 virus. 1117 64

Cyclosporin A (CsA) blocks T cell activation by interfering with the Ca2+-dependent phosphatase, calcineurin. Proinflammatory responses to bacteria that are activated by Ca2+-fluxes in airway cells are a potential target for CsA. Although local immunosuppression may be advantageous to control airway inflammation, it could also increase susceptibility to bacterial pneumonia and invasive infection. As aerosolized CsA is currently under study in lung transplantation, we examined its direct effects on airway cells as well as in a murine model of pneumonia. Epithelial interleukin-6 production was very effectively inhibited by CsA, whereas CXCL8 production, the major PMN chemokine, was only modestly diminished. Responses to a TLR2 agonist Pam3Cys were more sensitive to CsA inhibition than those activated by Pseudomonas aeruginosa. CsA substantially blocked activation of nuclear factor of activated T cells and cAMP-responsive element-binding protein (P<0.001), inhibited CCAAT/enhancer-binding protein by 50% (P<0.05), and minimally blocked activator protein-1 and nuclear factor-kappaB responses to bacteria in epithelial cells. The in vitro effects were confirmed in a mouse model of P. aeruginosa infection with similar rates of PMN recruitment, pneumonia and mortality in CsA treated and control mice. These studies indicate that airway epithelial signaling is a potential target for CsA, and such local immunosuppression may not increase susceptibility to invasive infection.
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PMID:The effect of cyclosporin A on airway cell proinflammatory signaling and pneumonia. 1587 61

Plasma levels of high mobility group box chromosomal protein-1 (HMGB-1), as well as of other inflammatory molecules such as interleukin-6 (IL-6), regulated on activation normal T-cell expressed and secreted (RANTES), and soluble intercellular adhesion molecule-1 (sICAM-1), were determined in patients with bacterial pneumonia coinfected with influenza virus. HMGB-1 levels were significantly elevated in these patients compared to patients undergoing mild bacterial pneumonia alone (p < 0.01). Among cases of coinfection, we found a significant correlation between the concentration of HMGB-1 and white blood cell counts (p < 0.05, r = 0.612). Levels of IL-6 were also higher in these patients than in patients with bacterial pneumonia alone (p < 0.05), despite similar levels of RANTES and sICAM-1 in the 2 groups. These data suggest that HMGB-1 is involved in the pathogenesis of severe bacterial pneumonia coinfected with influenza virus.
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PMID:Elevated levels of high mobility group box chromosomal protein-1 (HMGB-1) in sera from patients with severe bacterial pneumonia coinfected with influenza virus. 1791 13

The acute-phase response is characterized by increased circulating levels of acute-phase proteins (APPs) generated by the liver. During bacterial pneumonia, APPs correlate with the severity of disease, serve as biomarkers, and are functionally significant. The kinetics and regulatory mechanisms of APP induction in the liver during lung infection have yet to be defined. Here we show that APP mRNA transcription is induced in the livers of mice whose lungs are infected with either Escherichia coli or Streptococcus pneumoniae, and that in both cases this induction occurs in tandem with activation in the liver of the transcription factors signal transducer and activator of transcription 3 (STAT3) and NF-kappaB RelA. Interleukin-6 (IL-6) deficiency inhibited the activation of STAT3 and the induction of select APPs in the livers of pneumonic mice. Furthermore, liver RelA activation and APP induction were reduced for mice lacking all signaling receptors for tumor necrosis factor alpha and IL-1. In a murine hepatocyte cell line, knockdown of either STAT3 or RelA by small interfering RNA inhibited cytokine induction of the APP serum amyloid A-1, demonstrating that both transcription factors were independently essential for the expression of this gene. These data suggest that during pneumonia caused by gram-negative or gram-positive bacteria, the expression of APPs in the liver depends on STAT3 activation by IL-6 and on RelA activation by early-response cytokines. These signaling axes may be critical for integrating systemic responses to local infection, balancing antibacterial host defenses and inflammatory injury during acute bacterial pneumonia.
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PMID:Mechanisms of the hepatic acute-phase response during bacterial pneumonia. 1928 7


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