Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper discusses the evaluation of new macrolides and new quinolones for the treatment of Legionnaires' disease in in vitro susceptibility test, penetration to polynuclear leukocytes and treatment in an animal model. Some kinds of biological response modifier (BRMs) such as granulocyte colony stimulating factor (GCSF), monocyte CSF (M-CSF), GM-CSF, recombinant interleukin-1 (IL-1) and IL-2 were also evaluated. The antimicrobial activity (MIC) of new macrolides to Legionella pneumophila (45 strains) showed the highest activity in TE-031 (Taisho Pharmaceutical Co., Tokyo, Japan) and then rokitamycin (RKM), RU-28965 (Roussel, France), erythromycin (EM), josamycin (JM) in decreasing order of activity. According to the results of the data of cell-penetration and survival rate after treatment of guinea pigs with experimental Legionella pneumonia, the new macrolides such as TE-031, RKM and RU-28965 are expected to be more effective in the treatment of Legionnaires' disease than EM. New quinolones such as ciprofloxatin (CPFX), NY-198 (Hokuriku Pharmaceutical Co., Japan) or T-3262 (Toyama Kagaku Pharmaceutical Co., Toyama Japan) were compared to ofloxacin (OFLX), enoxacin (ENX) or rifampin (RFP) for evaluation. These drugs showed excellent activity against L. pneumophila and good penetration to polynuclear leukocytes. Regarding the treatment of guinea pig with legionella pneumonia, OFLX was the most effective, and NY-198 or T-3262 were more effective than EM treatment. The highest survival rate was obtained with IL-2 in infected guinea pigs. We also observed the efficacy of combined use of IL-2 and HR-8 10 (Horchst FRG) which is a newly developed cephem antibiotic.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of severe respiratory infection. Legionella pneumonia]. 261 84

The inflammatory response and influence of T cell depletion on the pathogenesis of an experimental Legionella infection were studied. A/J mice were infected with 10(6) CFU of Legionella pneumophila intratracheally. With this dose all infected animals survived the infection and bacteria were cleared from lung, spleen, liver, and kidney within 10 to 11 days, leaving no residual changes in the affected organs. Inflammatory cells were recruited into the lung on the second day of infection, reaching a maximum on the third day and filling out predominantly the interstitial areas. During the first 3 days after inoculation, mainly macrophages, B cells, NK cells, and large mononuclear cells of an unknown phenotype were attracted into the lung interstitium, whereas T lymphocytes infiltrated subsequently. During the early phase of infection, serum concentrations of IFN-gamma, TNF-alpha, IL-1beta, IL-4, and IL-6 but not IL-2 increased dramatically. The cytokine secretion decreased on the third day after infection although bacteria were still present in the lung or even disseminated in different organs. Successful clearance of bacteria from the lung was not observed before recruitment of T cells into the lung. In mice depleted of both CD4+ and CD8+ T cells, control of infection was impaired and lethality of infection increased. Depletion of either subset left residual antibacterial mechanisms, which, however, were not sufficient to clear the Legionella as rapidly as in undepleted mice.
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PMID:Legionella pneumophila infection in intratracheally inoculated T cell-depleted or -nondepleted A/J mice. 955 86

Legionella pneumophila causes community-acquired pneumonia with high mortality, but little is known about its interaction with the alveolar epithelium. The aim of this study was to investigate whether L. pneumophila infection of lung epithelial cells (A549) resulted in pro-inflammatory activation. L. pneumophila infection induced liberation of interleukin (IL)-2, -4, -6, -8 and -17, monocyte chemoattractant protein-1, tumour necrosis factor-alpha, IL-1beta, interferon-gamma and granulocyte colony-stimulating factor, but not of IL-5, -7, -10, -12 (p70) or -13 or granulocyte-macrophage colony-stimulating factor. The present study focused on IL-8 and found induction by L. pneumophila strains 130b, Philadelphia 1, Corby and, to a lesser extent, JR32. Knockout of dotA, a central gene involved in type IVB secretion, did not alter IL-8 induction, whereas lack of flagellin significantly reduced IL-8 release by Legionella. Moreover, p38 mitogen-activated protein kinase (MAPK) was activated and kinase inhibition reduced secretion of induced cytokines, with the exception of IL-2 and granulocyte colony-stimulating factor. In contrast, inhibition of the MAPK kinase 1/extracellular signal-regulated kinase pathway only reduced the expression of a few cytokines. L. pneumophila also induced binding of nuclear factor-kappaB subunit RelA/p65 and RNA polymerase II to the il8 promoter, and a specific inhibitor of the inhibitor of nuclear factor-kappaB complex dose-dependently lowered IL-8 expression. Taken together, Legionella pneumophila activated p38 mitogen-activated protein kinase- and nuclear factor-kappaB/RelA pathway-dependent expression of a complex pattern of cytokines by human alveolar epithelial cells, presumably contributing to the immune response in legionellosis.
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PMID:Legionella pneumophila-induced NF-kappaB- and MAPK-dependent cytokine release by lung epithelial cells. 1697 6

Soluble MHC antigens are detected in body fluids but their role and origin are still unclear. This study examined whether serum IA antigens, isolated from BALB/c mice (sIA(d)), could modulate the immune response. Specific purification procedures isolated intact IA molecules, which were thereafter applied to functional assays. Thus, sIA(d) were shown to stimulate spleen cell proliferation and the major target was identified to be the CD4(+) cell population. Inhibition of the CD4 co-receptor using specific neutralizing antibodies destroyed the sIA(d)-mediated proliferative activity, while sIA(d) successfully antagonized surface IA(d) antigens for binding to anti-IA(d) antibody. Serum-IA(d) stimulated BALB/c versus C3H/HeN but not C3H/HeN versus BALB/c mixed lymphocyte reactions, while increasing responsiveness to Legionella pneumophila. However, sIA(d) displayed an inhibitory activity during the effector phase of the humoral response, since they inhibited the anti-DNP-specific IgM production to a DNP-HSA hapten-carrier system. Furthermore, sIA(d) molecules increased Th1/Th2 cytokines during the L. pneumophila stimulus, while decreasing IL-2, GM-CSF and increasing IL-4, IL-15 during the DNP-HSA stimulus. These results suggest that sIA(d), following steps similar to surface class II antigen binding mechanisms, stimulate the initiation of a humoral or cellular immune response but rather inhibit the effector phase of the reactions, attributing thus soluble class II MHC antigens important immunomodulatory roles.
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PMID:Serum-derived MHC class II molecules: potent regulators of the cellular and humoral immune response. 1945 70