Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031154 (peritonitis)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intact peritoneal macrophage (M phi) function is critical to successful localization of intra-abdominal infection. Peritoneal macrophage antigen presentation capacity (APC), interleukin-1 (IL-1) expression, and immune-associated (Ia) antigen expression and abscess formation were determined following cecal ligation and puncture. APC and IL-1 expression were measured by coculture with a T-helper cell clone and by measuring subsequent proliferation. Ia expression was determined in blood, peritoneal M phi, and splenocytes using anti-Ia monoclonal antibody stain and flow cytometric analysis. Significant reductions in both Ia expression and APC were found 1 and 4 days after CLP with no change in IL-1 expression. Muramyl dipeptide, which enhances M phi phagocytosis, partially abrogated the depression in antigen presentation but did not affect Ia expression. Peritoneal M phi Ia expression and APC, but not IL-1 expression, were depressed after experimental peritonitis. The recovery of M phi function by day 14 coincides with clinical recovery and abscess formation, and restoration of early M phi depression may improve outcome.
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PMID:Alteration of mononuclear cell immune-associated antigen expression, interleukin-1 expression, and antigen presentation during intra-abdominal infection. 774 31

Hepatic dysfunction is a major contributor to death in multiple organ system failure. To evaluate whether this dysfunction increases with the length of sepsis, we studied the effect of fulminant CLP peritonitis with hyperoxia on mixed-function oxidase-MFO (cytochrome P450 content and activity) and lipid peroxidation in rat livers. Livers were harvested at 18, 21, 24, and 27 hr, homogenized, and microsomal fractions prepared. Cytochrome P450 concentration was determined by assay and P450 activity was determined by the metabolism of ethoxyresorufin and ethoxycoumarin. Lipid peroxidation was estimated by measuring malondialdehyde content. Septic rats showed decreases in P450 levels and activity, which worsened with duration of sepsis. These decreases were partially lessened by hyperoxia. Although there was a trend toward increased lipid peroxidation, this effect was not statistically significant. This study suggests that while MFO content and activity decrease with sepsis, these decreases do not appear to be related to the production of oxygen-derived free radicals. Furthermore, hyperoxia actually appears to have a protective role in this instance.
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PMID:Mixed-function oxidase activity in sepsis. 853 82

The hemodynamic effects of sepsis have been attributed in part to increased nitric oxide (NO) production and activation of guanylate cyclase, resulting in increased cGMP and relaxation of vascular smooth muscle. Heme oxygenase-1 (HO-1), a heat shock protein, has been shown to increase intracellular cGMP levels by formation of carbon monoxide (CO). We hypothesized that HO may be an important mediator of the hepatic response to infection. Male Swiss Webster mice underwent standard cecal ligation and puncture (CLP, 18 gauge 2X) or sham operation, and received either normal saline (NS) or Zn protoporphyrin IX (ZN PP IX), a competitive HO inhibitor (n = 6-8/group). Hepatic tissue samples were collected at 3, 6, 12, and 24 hr from separate mice. Serum was collected at 3 and 24 hr. A semiquantitative reverse transcriptase polymerase chain reaction method was used to measure HO-1 mRNA levels. Hepatic cGMP levels were measured by ELISA. Groups were repeated (n = 10/group) to assess mortality. Serum was collected at 3 and 24 hr to measure serum aspartate aminotransferase (AST) levels. HO-1 mRNA expression increased significantly by 3 hr after CLP and with HO inhibition alone (P < 0.05 vs sham + NS). HO-1 mRNA remained elevated through 24 hr. CLP animals with HO inhibition showed a significant reduction of hepatic cGMP following CLP compared with CLP + saline at 24 hr (P < 0.05). Mortality was significantly increased in the CLP + ZN PP group at 24 hr (P < 0.05 CLP NS vs CLP ZN PP). CLP caused a marked increase in AST activity, which was increased further with HO inhibition. HO-1 mRNA expression was induced by CLP. AST levels following CLP were markedly increased with HO inhibition. HO-1 function appeared to contribute to elevation of hepatic cGMP during peritonitis and may be an important hepatic adaptive response to infection.
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PMID:Heme oxygenase-dependent carbon monoxide production is a hepatic adaptive response to sepsis. 927 Dec 71

The occurrence of peritoneal adhesions in surgical patients is positively correlated with tumor necrosis factor (TNF) levels. In a model of septic peritonitis-cecal ligation and puncture-TNF neutralization prevented formation of peritoneal adhesions and increased mortality, most likely because localization of the septic focus was prevented. To discriminate between the coagulation-independent protective TNF effect and a potential protective procoagulant TNF effect, formation of peritoneal adhesions after CLP was inhibited with heparin, hirudin, or urokinase. Each treatment increased mortality and increased the number of bacteria in the peritoneal lavage fluid, kidney, and liver to various degrees. Under these experimental conditions, antibiotics prevented death. In coagulation-compromised mice, lethality was further enhanced by additional TNF neutralization. These findings demonstrate that peritoneal adhesions early in septic peritonitis are an important mechanism of innate immunity that prevents increased spread of bacteria and reduces mortality.
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PMID:Tumor necrosis factor-dependent adhesions as a major protective mechanism early in septic peritonitis in mice. 1134 12

Cardiac myocytes isolated from rats with peritonitis (cecal ligation and perforation; CLP) promote PMN transendothelial migration. Herein, we assessed (1) the mechanisms involved in cardiac myocyte activation during peritonitis and (2) the means by which these activated myocytes promote PMN transendothelial migration. Plasma obtained from mice subjected to CLP (septic plasma) activated isolated cardiac myocytes as evidenced by (1) increased nuclear levels of nuclear factor-kappaB (NF-kappaB) and (2) their ability to promote PMN migration across endothelial cell monolayers. Pretreatment of septic plasma with an antibody against tumor necrosis factor-alpha (TNF-alpha), but not interleukin-1beta (IL-1beta), blunted the ability of septic plasma to activate the myocytes. However, septic plasma obtained from TNF-alpha-deficient mice could still activate the myocytes; an effect attenuated by an antibody against IL-1beta. If the myocytes were pretreated with a proteasome inhibitor (MG 132) to prevent NF-kappaB activation, the myocyte-induced PMN transendothelial migration was compromised. The activated myocytes released platelet-activating factor (PAF), and myocyte-induced PMN migration was abrogated by a PAF receptor antagonist (WEB 2086). These myocytes also released the CXC chemokines LIX and KC; an event prevented by MG 132. Antibodies against LIX and KC abrogated the myocyte-induced PMN migration. However, LIX and KC, but not PAF, could promote PMN migration when used at concentrations produced by activated myocytes. These observations indicate that TNF-alpha and IL-1beta are, in part, responsible for the ability of septic plasma to activate cardiac myocytes. The activated myocytes promote PMN transendothelial migration, an effect attributable to LIX and KC, and possibly, PAF.
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PMID:Cardiac myocytes activated by septic plasma promote neutrophil transendothelial migration: role of platelet-activating factor and the chemokines LIX and KC. 1498 31

In an isolated perfused lung model, bradykinin induced pulmonary vasoconstriction in rats made septic by the injection of lipopolysaccharide (LPS). To mimic the pathophysiology of sepsis in humans more closely, we investigated pulmonary endothelial injury in a peritonitis model (cecal ligation and perforation; CLP). Male Sprague-Dawley rats were randomly divided into nine groups (n = 6-8). LPS and CLP rats were compared after 6 h with and without treatment with a selective inhibitor of inducible nitric oxide synthase (iNOS), L-N(6)-(1-iminoethyl)-lysine. Time dependency was investigated in CLP-treated rats at 24 h. The pulmonary circulation was isolated and perfused with a constant flow after the rats' tracheas were intubated and ventilated. Bradykinin (1, 3, and 6 microg) was injected, and changes in perfusion pressure were measured. Lungs were harvested for Western blot analysis to determine the role of iNOS in pulmonary endothelial dysfunction. In contrast to CLP 24 h rats, dose-dependent bradykinin-induced pulmonary vasoconstriction was observed in LPS and CLP 6 h rats. Concomitant administration of L-N(6)-(1-iminoethyl)-lysine significantly attenuated this vasoconstriction in both groups. The iNOS protein was expressed in lung homogenates from LPS 6 h and CLP 6 h but not from CLP 24 h rats. Both sepsis models caused bradykinin-induced pulmonary vasoconstriction, with the CLP groups demonstrating a time dependency of this effect. In conjunction with the time-dependent decrease in iNOS protein, the attenuated bradykinin-induced vasoconstriction due to selective iNOS inhibition suggests an important role for iNOS in pulmonary endothelial injury for both sepsis models.
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PMID:Bradykinin-induced pulmonary vasoconstriction is time and inducible nitric oxide synthase dependent in a peritonitis sepsis model. 1533 23

Highly activated neutrophils play a critical role in mediating organ injury in sepsis by releasing neutrophil elastase (NE). Toll-like receptors (TLRs) play an important role in the host defense against invading microbes, and their signaling pathway is critical to the activation of the proinflammatory response. However, the relationship between TLR expression and the host defense mechanism during sepsis has not been fully elucidated. In this paper, we investigated the relationships among chemokine (MIP-2), TLR-4, and NE expression in human sepsis and murine peritonitis (CLP). TLR-4 expression on monocytes/macrophages was examined in patients with sepsis and in murine peritonitis and was markedly increased in both populations. LPS-induced MIP-2 production by bronchoalveolar cells and liver mononuclear cells in mice with peritonitis was also significantly increased compared with sham-operated mice. Pretreatment of the macrophage cell line, RAW 264.7 cells, with a NE inhibitor before their exposure to LPS resulted in a significant dose-dependent decrease in MIP-2 production, which was comparable to that seen following pretreatment with TLR-4 antibody. Furthermore, NE and LPS both up-regulated TLR-4 expression on human peripheral blood monocytes. Thus, chemokine-induced recruitment of neutrophils in sepsis may result in further increased chemokine production and increased expression of TLR-4. Neutrophil-derived NE may be associated with increased expression of monocyte/macrophage TLR-4, thereby serving as a positive feedback loop for the inflammatory response among the different cell populations.
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PMID:Neutrophil elastase, MIP-2, and TLR-4 expression during human and experimental sepsis. 1561 30

Central nervous system dopaminergic mechanisms have been implicated in the cytokine response to stress and sepsis. We here describe the effects of haloperidol or clozapine in the treatment of sepsis induced by cecal ligation and puncture. Male Wistar rats were subjected to the CLP procedure were treated with haloperidol or clozapine and plasma cytokines, myeloperoxidase activity, markers of organ injury and survival was analyzed. The addition of haloperidol or clozapine to basic support did not diminished hepatic, renal, pancreatic or muscular damage observed after sepsis. Neither haloperidol, nor clozapine, modulates pro and antiinflammatory cytokines after sepsis induction. In addition, haloperidol treatment did not diminished myeloperoxidase activity in the kidney, lung or liver, or altered BALF markers of lung damage or inflammatory infiltration. Our data did not support a role of haloperidol or clozapine as an immunomodulator agent in the treatment of sepsis in an animal model of peritonitis.
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PMID:Lack of effect of dopaminergic antagonists in a rodent model of peritoneal sepsis. 1746 5

HSA preparations for i.v. use are administered in critically ill patients. Although increasing intravascular osmotic pressure seems to be a pathophysiologically orientated treatment, clinical trials do not indicate a benefit for mortality in HSA-treated patients. Instead, there is evidence for inflammatory reactions upon infusion of different HSA batches. A neglected issue concerning the safety and quality of these therapeutics is processing-related post-transcriptional protein modifications, such as AGEs. We therefore tested the hypothesis that commercially available infusion solutions contain AGEs and studied whether these protein modifications influence outcome and inflammation in a murine model of sepsis induced by CLP. Screening of different HSA and Ig preparations in this study revealed an up to approximate tenfold difference in the amount of AGE modifications. Application of clinically relevant concentrations of CML-modified HSA in CLP led to increased inflammation and enhanced mortality in wild-type mice but not in mice lacking the RAGE. Lethality was paralleled by increased activation of the proinflammatory transcription factor NF-kappaB, NF-kappaB-dependent gene expression, and infiltration of inflammatory cells in the peritoneal cavity. This study implies that infusion solutions containing a high load of the AGE-modified protein have the potential to activate RAGE/NF-kappaB-mediated inflammatory reactions, causing increased mortality in experimental peritonitis.
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PMID:AGE-modified albumin containing infusion solutions boosts septicaemia and inflammation in experimental peritonitis. 1972 Jun 16

Septic peritonitis remains a major cause of death. Neutrophils and inflammatory monocytes are principal components of the innate immune system and are essential for defense against a range of microbial pathogens. Their role and interaction in polymicrobial sepsis have not been defined clearly. Using a murine model of CLP to induce moderate sepsis, we found that neutrophil depletion did not alter survival, whereas depletion of neutrophils and inflammatory monocytes markedly reduced survival. After neutrophil depletion, inflammatory monocytes had greater phagocytic capacity and oxidative burst, and increased expression of costimulatory molecules, TNF, and iNOS. Notably, peritoneal neutrophils produced IL-10 following CLP. Adoptive i.p. transfer of WT but not IL-10(-/-) neutrophils into septic mice reduced monocyte expression of TNF. In vitro experiments confirmed that monocyte suppression was mediated by neutrophil-derived IL-10. Thus, during septic peritonitis, neutrophils suppress peritoneal inflammatory monocytes through IL-10 and are dispensable for survival.
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PMID:Neutrophil IL-10 suppresses peritoneal inflammatory monocytes during polymicrobial sepsis. 2110 42


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