Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0341503 (bacterial peritonitis)
 1,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) is produced by various cell types, and it is an important mediator in many biological processes, including macrophage-mediated cellular host defense. The relevance and amount of NO production in peritonitis during peritoneal dialysis (PD) treatment is still not clear. We studied whether human peritoneal macrophages (PMphi) isolated from healthy PD patients or PD patients with peritonitis showed different spontaneous or lipopolysaccharide (LPS)/interferon gamma (IFN-gamma)-induced NO production (LPS, 1 ng/mL-10 microg/mL; IFN-gamma, 10-1000 U/mL; incubation between 6-48 hours; measured by Griess reagent). Results were compared with human blood monocytes (HBM) isolated from buffy coats. Inducible nitric oxide synthetase (iNOS) mRNA expression was looked for in PMphi by reverse transcriptase polymerase chain reaction (RT-PCR). Furthermore, plasma (P) and peritoneal dialysate effluent (D) nitrite concentrations were measured in vivo. The dialysate-to-plasma ratio (D/P) of nitrite concentration was inverse in the case of peritonitis compared to infection-free patients (peritonitis D/P = 1.3, non peritonitis D/P = 0.4; p < 0.01). PMphi from peritonitis patients produced higher amounts of NO than did those from infection-free patients (0.040+/-0.044 nmol per microgram cell protein versus 0.018+/-0.015 nmol per microgram cell protein, p < 0.05). NO release could not be further enhanced by stimulation with LPS plus IFN-gamma (1 ng/mL, 250 U/mL, respectively). However, NO production in PMphi from infection-free patients increased during in vitro stimulation (0.044+/-0.031 nmol per microgram cell protein versus 0.018+/-0.015 nmol per microgram cell protein, p < 0.01). An increase of iNOS mRNA expression could be demonstrated by RT-PCR. Blood monocytes from healthy donors also increased NO release during cytokine stimulation (0.032+/-0.015 nmol per microgram cell protein versus 0.019+/-0.009 nmol per microgram cell protein, p < 0.05). Our results indicate that significant amounts of NO are released intraperitoneally in the case of bacterial peritonitis. PMphi represent a site of NO production, though the absolute amounts released in vitro are only moderate. NO production can be induced in PMphi and HBM by LPS/IFN-gamma stimulation in vitro.
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PMID:Nitric oxide production in peritoneal macrophages from peritoneal dialysis patients with bacterial peritonitis. 1040 50

Identification of new therapeutic targets for the management of septic shock remains imperative as all investigational therapies, including anti-tumor necrosis factor (TNF) and anti-interleukin (IL)-1 agents, have uniformly failed to lower the mortality of critically ill patients with severe sepsis. We report here that macrophage migration inhibitory factor (MIF) is a critical mediator of septic shock. High concentrations of MIF were detected in the peritoneal exudate fluid and in the systemic circulation of mice with bacterial peritonitis. Experiments performed in TNFalpha knockout mice allowed a direct evaluation of the part played by MIF in sepsis in the absence of this pivotal cytokine of inflammation. Anti-MIF antibody protected TNFalpha knockout from lethal peritonitis induced by cecal ligation and puncture (CLP), providing evidence of an intrinsic contribution of MIF to the pathogenesis of sepsis. Anti-MIF antibody also protected normal mice from lethal peritonitis induced by both CLP and Escherichia coli, even when treatment was started up to 8 hours after CLP. Conversely, co-injection of recombinant MIF and E. coli markedly increased the lethality of peritonitis. Finally, high concentrations of MIF were detected in the plasma of patients with severe sepsis or septic shock. These studies define a critical part for MIF in the pathogenesis of septic shock and identify a new target for therapeutic intervention.
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PMID:Protection from septic shock by neutralization of macrophage migration inhibitory factor. 1065 4

Fever, a nonspecific acute-phase response, has been associated with improved survival and shortened disease duration in infections, but the mechanisms of these beneficial responses are poorly understood. We previously reported that increasing core temperature of bacterial endotoxin (LPS)-challenged mice to the normal febrile range modified expression of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-6, three cytokines critical to mounting an initial defense against microbial pathogens, but survival was not improved in the warmer animals. We speculated that our inability to show a survival benefit of optimized cytokine expression in the warmer animals reflected our use of LPS, a nonreplicating agonist, rather than an infection with viable pathogens. The objective of this study was to determine if increasing murine core temperature altered cytokine expression and improved survival in an experimental bacterial peritonitis model. We showed that housing mice at 35.5 degrees C rather than 23 degrees C increased core temperature from 36.5 to 37.5 degrees C to 39.2 to 39.7 degrees C, suppressed plasma TNF-alpha expression for the initial 48 h, delayed gamma interferon expression, improved survival, and reduced the bacterial load in mice infected with Klebsiella pneumoniae peritonitis. We showed that the reduced bacterial load was not caused by a direct effect on bacterial proliferation and probably reflected enhanced host defense. These data suggest that the increase in core temperature that occurs during bacterial infections is essential for optimal antimicrobial host defense.
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PMID:Febrile core temperature is essential for optimal host defense in bacterial peritonitis. 1067 36

Continuous ambulatory peritoneal dialysis (CAPD) has emerged as an important dialysis treatment modality worldwide. One of the major complications is bacterial peritonitis, which may result in subsequent technique failure because of loss of peritoneal clearance or peritoneal fibrosis. Bacterial peritonitis leads to the release of proinflammatory cytokines from resident and infiltrating cells in the peritoneal cavity. We studied 35 patients undergoing CAPD with acute bacterial peritonitis. All patients treated with antibiotics for 2 weeks after the clinical diagnosis of peritonitis had a good recovery. Peritoneal dialysate effluent (PDE) was collected on days 1, 3, 5, 10, 21, and 42 after the start of treatment. Cell populations were monitored by flow cytometry. PDE levels of interleukin-1beta (IL-1), IL-6, transforming growth factor-beta (TGF-beta), and basic fibroblast growth factor (FGF) were measured by enzyme-linked immunosorbent assay. Gene transcription of TGF-beta in macrophages from PDE was measured by quantitative polymerase chain reaction. Bacterial peritonitis was associated with a sharp increase in total cell and neutrophil counts (400-fold) in PDE up to 3 weeks after peritonitis despite clinical remission (P < 0.0001). There was an increased absolute number of macrophages during the first 3 weeks despite the reduced percentage of macrophages among total cells in PDE compared with noninfective PDE. There was a progressive increase in the percentage of mesothelial cells or dead cells in the total cell population in PDE over the entire 6-week period. PDE levels of IL-1, IL-6, TGF-beta, and FGF increased markedly on day 1 before their levels decreased gradually. PDE levels of these cytokines or growth factors were significantly greater than those in noninfective PDE (n = 76) throughout the study period (P < 0.01). Similarly, TGF-beta complementary DNA (cDNA) molecules per macrophage were significantly greater than those of macrophages in noninfective PDE throughout this period (P < 0.01). There was no significant correlation between PDE levels of TGF-beta and TGF-beta cDNA molecules per macrophage, suggesting that peritoneal macrophages are not the only source of TGF-beta in PDE. We conclude there is an active release of proinflammatory cytokines and sclerogenic growth factors through at least 6 weeks despite apparent clinical remission of peritonitis. The peritoneal cytokine networks after peritonitis may potentially affect the physiological properties of the peritoneal membrane.
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PMID:Changes of cytokine profiles during peritonitis in patients on continuous ambulatory peritoneal dialysis. 1073 85

Human peritoneal mesothelial cells (HMCs) have a critical role in maintaining the intraperitoneal balance between fibrinolysis and coagulation by expressing the fibrinolytic enzyme, tissue-type plasminogen activator (tPA), as well as a specific plasminogen activator inhibitor (type 1; PAI-1). During bacterial peritonitis, the balance between intraperitoneal generation and degradation of fibrin is disturbed. As a consequence, severe peritoneal damage occurs, which is one of the leading causes of patient dropout from continuous ambulatory peritoneal dialysis (CAPD) therapy. Cultured HMCs isolated from omental biopsy specimens were used to study the effect of heat-killed strains (2 x 10(8)/mL) of Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli on the synthesis of tPA and PAI-1. Conditioned media were obtained by incubating cells with the different bacterial strains. tPA and PAI-1 antigen concentrations were measured in the cell supernatants by enzyme-linked immunosorbent assay. Each of the three heat-killed microorganisms induced a time-dependent increase in PAI-1 synthesis. After a 48-hour incubation period, the strongest effect was seen in the presence of S aureus (3.5-fold versus control), followed by S epidermidis (2.5-fold versus control) and E coli (1.5-fold versus control). Under the same conditions, tPA antigen levels did not change after exposure to S aureus or E coli, whereas the addition of S epidermidis resulted in enhanced tPA antigen production (2-fold versus control). The increase in PAI-1 synthesis in the presence of the heat-killed microorganisms was preceded by similar changes in interleukin-1alpha (IL-1alpha) levels. Inhibiting the activity of IL-1alpha with a neutralizing antibody significantly reduced bacterial-induced PAI-1 production. Our results indicate that the fibrinolytic imbalance during bacterial peritonitis depends on the bacterial species. The increase in PAI-1 synthesis, not the decrease in the production of tPA, alters mesothelial fibrinolytic activity. Because the increase in PAI-1 expression is significantly quenched by blocking the activity of IL-1alpha, the mesothelial release of this cytokine is involved in bacterial-induced changes in the fibrinolytic system.
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PMID:Heat-killed microorganisms induce PAI-1 expression in human peritoneal mesothelial cells: role of interleukin-1alpha. 1127 82

Discovered in the early 1960s as a T-cell cytokine, MIF has emerged to be an important mediator of the innate immune system. MIF was identified recently to be released by a vast array of cells, including monocytes/macrophages, T-cells, B-cells, endocrine cells and epithelial cells in response to infection and stress. Bacteria, microbial toxins and cytokines have been shown to be powerful inducers of MIF secretion by macrophages. MIF stimulates the expression of pro-inflammatory mediators by immune cells and functions to counterbalance the anti-inflammatory and immunosuppressive effects of glucocorticoids. Like TNF and IL-1, MIF plays an important role in host responses to infection. Recombinant MIF was found to exacerbate lethal endotoxemia or bacterial sepsis when co-injected with LPS or Escherichia coli in mice. Conversely, MIF knockout mice or mice treated with anti-MIF antibodies were protected from shock induced by LPS, staphylococcal exotoxins or bacterial peritonitis, even when anti-MIF therapy was started after the onset of infection. Given the central role played by MIF in innate immune responses against microbial pathogens and in the regulation of inflammatory responses, pharmacological modulation of MIF production or neutralization of MIF activity could have broad clinical applications and may offer new treatment options for the management of patients with severe sepsis or septic shock.
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PMID:Macrophage migration inhibitory factor (MIF) modulates innate immune responses induced by endotoxin and Gram-negative bacteria. 1175 17

The aim was to study in vitro regulation of the IL-5 receptor alpha (IL-5R alpha) on purified peripheral blood eosinophils from healthy subjects. The IL-5R alpha was down-regulated, in a dose-dependent manner, by recombinant IL-5 and GM-CSF, with IL-5 being most potent. This down-regulation was not induced by autocrine release of GM-CSF or IL-5, respectively. Incubation of eosinophils with cell-free peritoneal dialysis fluid (PF) collected from a patient with peritoneal fluid eosinophilia (PFE), induced up-regulation of the proportion of CD69 positive eosinophils, in parallel with down-regulation of the proportion of IL-5R alpha positive eosinophils. Experiments with neutralizing antibodies against IL-5 and GM-CSF, revealed that IL-5 was the principal cytokine responsible for the down-regulation of the IL-5R alpha. When eosinophils were incubated with PF collected from the same patient in remission or with PF collected from a newly started patient or a patient with bacterial peritonitis, less down-regulation of the IL-5R alpha was observed. In conclusion our data indicate that IL-5, as opposed to its proposed action on eosinophil progenitors, down-regulates the IL-5R alpha chain on mature eosinophils. We therefore suggest that an IL-5 driven inflammation generates an eosinophil tissue phenotype that is characterized by a low IL-5R alpha expression. These aspects of IL-5 action on IL-5R alpha expression could gain new insights into the mechanisms of specific immuno-modulatory therapies, such as anti-IL-5.
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PMID:Regulation of the interleukin-5 receptor alpha-subunit on peripheral blood eosinophils from healthy subjects. 1251 89

The reductive-oxidative status of tissues regulates the expression of many inflammatory genes that are induced during gram-negative bacterial infections. The cytokine gamma interferon (IFN-gamma) is a potent stimulus for host inflammatory gene expression, and oxidative stress has been shown to inhibit its production in mice challenged with Escherichia coli bacteria. The objective of the present study was to characterize the cells that produced IFN-gamma in a mouse bacterial peritonitis model and determine the effects of oxidative stress on their activation. The liver contained large numbers of IFN-gamma-expressing lymphocytes following challenge with viable E. coli bacteria. The surface phenotypes of IFN-gamma-expressing hepatic lymphocytes were those of natural killer (NK) cells (NK1.1(+) CD3(-)), conventional T cells (NK1.1(-) CD3(+)), and NK T cells (NK1.1(+) CD3(+)). Treating mice with diethyl maleate to deplete tissue thiols significantly impaired IFN-gamma production by NK cells, conventional T cells, and CD1d-restricted NK T cells in response to E. coli challenge. However, IFN-gamma expression by a subset of NK T cells, which did not bind alpha-galactosylceramide-CD1d tetramers, was resistant to the inhibitory effects of tissue oxidative stress. Stress-resistant IFN-gamma-expressing cells were also predominantly CD8(+) and bore gamma delta T-cell antigen receptors. The residual IFN-gamma response by NK T cells may explain previous reports of hepatic gene expression following gram-negative bacterial challenge in thiol-depleted mice. The finding also demonstrates that innate immune cells differ significantly in their responses to altered tissue redox status.
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PMID:Gamma interferon production by hepatic NK T cells during Escherichia coli infection is resistant to the inhibitory effects of oxidative stress. 1270 18

The cytokine macrophage migration inhibitory factor (MIF) has emerged recently as an important mediator of inflammation and innate immunity. MIF is rapidly released by macrophages after stimulation with microbial products and pro-inflammatory cytokines and, in turn, stimulates the production of pro-inflammatory mediators by immune cells. Immunoneutralization of MIF or deletion of the Mif gene was shown to protect animals from lethal endotoxemia, staphylococcal toxic shock and septic shock in experimental models of bacterial peritonitis. To investigate the function of MIF in innate immunity, we studied the response of macrophages expressing reduced levels of MIF to microbial products. These cells were generated by transduction of an antisense MIF adenovirus or by stable transfection with an antisense MIF plasmid or were obtained from MIF-knockout mice. MIF-deficient macrophages were shown to be hyporesponsive to stimulation with LPS and Gram-negative bacteria. The defect was associated with a down-regulation of Toll-like receptor 4 (TLR4), the signal transducing molecule of the LPS receptor complex. Immunoneutralization of extracellular MIF decreased TLR4 expression and responses of macrophages to LPS, indicating that MIF may exert autocrine effects. These findings identify an important role for MIF in innate immunity and provide a rationale for the development of anti-MIF strategy for the treatment of patients with Gram-negative septic shock.
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PMID:Macrophage migration inhibitory factor (MIF) regulates host responses to endotoxin through modulation of Toll-like receptor 4 (TLR4). 1280 86

Suppression of cellular immunity secondary to decreased immunocyte function is one of the surgical stress-induced biological responses. Monocytes/macrophages, natural killer (NK) cells, lymphocytes, and neutrophils play an important role in this immune system. These immunity charge cells are expressed through various surface antigens, such as major histocompatibility complex (MHC) class antigens, T cell receptors, and the cytokines interferon-gamma, interleukin (IL)-2, and IL-12. MHC class II antigen expression of monocytes and the cytokine production of CD4+ T cells are decreased after surgical stress. In this immune-suppressed condition, patients after surgical stress can easily experience infectious complications, and therefore the up-regulation of the immune system is necessary to avoid those complications. Recently, the role of natural immunity as a defense system against infection has received attention. The discovery of Toll-like receptor families revealed how the macrophage system cells recognize microorganisms. Furthermore, liver natural killer(NK) cells and NK T cells are important to induce the Th1 immune response in bacterial peritonitis. In this manuscript, we explain the mechanism of immune suppression after surgical stress and the host defense against infection by analyzing cytokine production and surface membrane molecules in mononuclear cells.
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PMID:[Mechanism of immune suppression after surgical stress and host defense against infection]. 1473 64


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