Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro functions of stimulated peripheral T cells and monocytes were investigate in patients experiencing sepsis following major visceral surgery. Cell culture supernatants were analyzed by ELISA for IL-2, IFN-gamma, IL-4, IL-10, TNF-alpha, IL-1 beta, and IL-12p40. In addition, monocyte HLA class II expression was determined by flow cytometry. T cell secretion of IL-2, TNF-alpha, and in part IFN-gamma (but not IL-4) was significantly diminished in non-survivors throughout the entire course of sepsis, compared to controls and sepsis survivors. Production of IL-1 beta and IL-12 p40 by monocytes was strongly reduced in both survivors and non-survivors at the onset of sepsis. Persistence of depressed monocyte cytokine secretion correlated with lethality. Thus, overall suppression of cytokine production by T cells and monocytes was already observed at the beginning of postoperative sepsis. HLA class II expression by monocytes exhibited a strong and sustained down-regulation with no significant differences between sepsis survivors and non-survivors. In summary, suppression of both T cell and monocyte functions develops early during postoperative sepsis. Recovery of immune functions and severity of immune defects are associated with outcome.
 ...
PMID:[Immune paralysis of T-lymphocytes and monocytes in postoperative abdominal sepsis. Correlation of immune function with survival]. 1073 84

Gram-negative bacteria acquired through gastrointestinal infection can be a serious cause for the development of septic shock especially in immunosuppressed patients. Thus, the aim of this study was to examine the early events of the immune reaction against S. typhimurium. Bacteria were injected into mice at different concentrations. Four animals from each group were killed at five different points of time. Liver cytokine mRNA expression was determined by semiquantitative rt-PCR and liver histology was examined. Serum cytokine levels of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-4 and IL-10 were determined. intravenous (i.v.) infection with 109 bacteria led to lethal septic shock within 24 h. A delayed production of IFN-gamma, TNF-alpha, IL-18 and IL-10 and milder histological alterations in the liver were observed in these animals. The highest expression of cytokines in the liver and the strongest histological alterations were seen after infection with 107 bacteria. Here, an increased mRNA expression of all proinflammatory cytokines began 1 h after infection. Animals infected with 1 x 102 bacteria had the highest detectable serum levels of IL-6 and IL-10. These data indicate that the immediate events in the immune reaction within the liver after infection with S. typhimurium are associated with the outcome of the subsequent sepsis.
 ...
PMID:The early immune response in the liver of BALB/c mice infected with S. typhimurium. 1079 38

The interleukins (IL)-1beta and IL-18 represent potent players in the proinflammatory cytokine cascade. Their activation is regulated predominantly through the IL-1-converting enzyme (ICE)/caspase-1. The role of caspases in the secretion of IL-1beta and IL-18, as well as in the release of the secondary-induced cytokines IL-12 and interferon (IFN)-gamma in whole blood from septic patients compared to healthy controls, was studied. Inhibition of caspase activity by Z-VAD significantly reduced lipopolysaccharide (LPS) and Staphylococcus aureus (SAC) induced release of mature IL-1beta in septic patients and controls. In contrast, in whole blood from septic patients significantly elevated basal level of IL-18 were found, which could neither be further increased by LPS or SAC, nor be inhibited by Z-VAD. Release of IL-12 p40 was significantly lower in septic patients compared to controls and was not affected by Z-VAD. Despite high levels of IL-18, IFN-gamma was not detected in whole blood from septic patients even after stimulation with SAC or LPS. Thus, during sepsis, caspases participate in the processing of IL-1beta, whereas maturation of IL-18 during sepsis appears to be independent of caspases. The lack of IFN-gamma release seen in septic patients could be attributed to low IL-12 release rather than to diminished IL-18 release.
 ...
PMID:Differential effect of caspase inhibition on proinflammatory cytokine release in septic patients. 1102 39

Studies have shown that immune responses are depressed in male mice, but not in proestrus females after trauma-hemorrhage (TH), resulting in increased mortality from subsequent sepsis in male mice compared with female mice. These gender-specific alterations in immune function are believed to be due to differences in sex steroid levels. Aromatase is a key enzyme in the sex steroid biosynthesis. Although earlier studies have shown that aromatase inhibitors prevent thymic atrophy in aged male rats, it remains unknown whether the use of 4-hydroxy-androstenedione (4-OHA) after TH in male mice has any salutary effects on the depressed immune responses. Male C3H/HeN mice were sham operated or subjected to trauma (i.e., midline laparotomy) and hemorrhagic shock (30+/-5 mmHg for 90 min) followed by adequate fluid resuscitation. 4-OHA (5 mg/kg) or vehicle was administrated s.c. just before resuscitation. At 2 h after resuscitation, the mice were killed, and spleens were harvested. Splenocyte proliferation, interleukin (IL-2), interferon (IFN-gamma), and IL-10 release and expression of androgen (AR) and estrogen receptors (ER)-alpha and -beta by immunoblot and reverse transcription-polymerase chain reaction (RT-PCR) were assessed. In another group, sepsis was induced by cecal ligation and puncture (CLP) 3 days after resuscitation, and survival was measured over a period of 10 days. A significant decrease in splenocyte proliferation, IL-2, and IFN-gamma release and increased release of IL-10 were observed in vehicle-treated mice. Animals treated with 4-OHA showed increased splenocyte proliferation, IL-2, and IFN-gamma release, and decreased IL-10 release. Immunoblot analysis showed decreased expression of the cytosolic AR, but no significant difference in the cytosolic and nuclear ER-alpha and -beta expression was observed in the vehicle-treated group after TH. In addition, AR and ER-beta mRNA expression was increased, whereas ER-alpha expression decreased in the vehicle-treated group after TH. ER-alpha expression decreased and ER-beta expression increased in the nucleus of 4-OHA treated mice as determined by immunoblot. There was no difference in the cytosolic AR expression in the 4-OHA-treated group after TH. AR and ER-beta mRNA expression was unaffected, whereas ER-alpha expression increased under such conditions. In additional groups, the increased mortality rate after TH and subsequent sepsis was significantly reduced by 4-OHA treatment. Thus, 4-OHA seems to be a novel and useful adjunct for restoring the depressed immune functions in males after TH and for decreasing mortality rates from subsequent sepsis.
 ...
PMID:The aromatase inhibitor, 4-hydroxyandrostenedione, restores immune responses following trauma-hemorrhage in males and decreases mortality from subsequent sepsis. 1102 55

Recent experimental studies have found gender differences in the immune response after hemorrhagic shock with an enhanced immune function and lower mortality after subsequent sepsis in females than in males. Interleukin-10 (IL-10) has been shown to play a potential role in the treatment of early proinflammatory state after hemorrhagic shock. Although studies showed beneficial effects of the treatment with IL-10, it remains unclear whether the effects are gender related. To study this, male and female CBA/J mice were subjected to hemorrhage (35+/-5 mmHg for 90 min and fluid resuscitation) or sham operation. At resuscitation, each received either recombinant murine IL-10 (rmIL-10) or placebo i.p. At 48 h after resuscitation, peritoneal macrophages (pMphi) and splenocytes were harvested. IL-1beta and IL-12 release by pMphi and splenocyte proliferation and splenocyte IL-2 and interferon (IFN)-gamma release capacity were assessed. Interleukin-10 plasma levels were not increased after rmIL-10 treatment. The results indicate that rmIL-10 treatment restores depressed immune response (splenocyte proliferation, IFN-gamma, IL-1beta in males after hemorrhagic shock. In contrast, the immune responses after shock in females were not influenced by rmIL-10, with the exception of depressed splenocyte proliferation. In addition, sham-operated male mice treated with rmIL-10 showed immune depression compared with the placebo group. Thus, administration of rmIL-10 during resuscitation after hemorrhage produces salutary effects on the depressed immune responses in males but did not further enhance the immune functions in females under those conditions.
 ...
PMID:Gender-related therapy: early IL-10 administration after hemorrhage restores immune function in males but not in females. 1102 56

Recent reports support the concept that the major defect in polymicrobial sepsis is an impaired immunologic response to infection. Oligodeoxynucleotides containing CpG sequence motifs (CpG-ODN) were previously shown to induce immune protection in models of chronic infection with intracellular bacteria, parasites, and viruses due to their ability to augment IFN-gamma-dependent Th1 responses. Here, we demonstrate that challenging mice with CpG-ODN substantially increases the resistance against acute polymicrobial sepsis. Systemic levels of IL-12, IL-18, and IL-10 were not altered in CpG-ODN-treated mice as compared with controls. In contrast, administration of CpG-ODN resulted in a strongly enhanced accumulation of neutrophils at the primary site of infection. Neutrophils of CpG-ODN-treated mice exhibited an up-regulation of phagocytic receptors, an increased phagocytic activity, and an elevated production of reactive oxygen metabolites. These results suggest that the protective effects of CpG-ODNs in acute polymicrobial sepsis are related to an enhanced effector cell response of innate immunity. CpG-ODN may therefore represent potent agents for the treatment of sepsis-associated immunoparalysis.
 ...
PMID:Increased resistance against acute polymicrobial sepsis in mice challenged with immunostimulatory CpG oligodeoxynucleotides is related to an enhanced innate effector cell response. 1103 94

In this study we investigated the capacity of morphine to modulate expression of cytokines in peritoneal macrophages. Mice were implanted subcutaneously with a 75-mg morphine slow-release pellet, and 48 h later resident peritoneal macrophages were harvested. Control groups received placebo pellets, naltrexone pellets, or morphine plus naltrexone pellets. Adherent cells were stimulated with lipopolysaccharide (LPS: 10 microg/mL) plus interferon-gamma (IFN-gamma: 100 units/mL) to induce cytokine production. After 24 h RNA was extracted for analysis of cytokine mRNA levels by reverse transcriptase-polymerase chain reaction, or supernatants were collected after 48 h for determination of cytokine production by enzyme-linked immunosorbent assay (ELISA). Morphine enhanced mRNA expression of interleukin (IL)-12 p40 and tumor necrosis factor alpha (TNF-alpha) compared with controls, whereas IL-10 levels were unchanged by drug treatment. ELISA data showed that both IL-12 p40 and p70 were increased by morphine. The enhancement of IL-12 at both the mRNA and protein levels was antagonized by naltrexone, indicating that the modulation of this cytokine by morphine is via a classic opioid receptor. These results are particularly interesting in light of our previous observation that 48 h after morphine pellet implantation, the peritoneal cavity is colonized with gram-negative and other enteric bacteria. The enhancement of IL-12 by morphine might be related to morphine-induced sepsis.
 ...
PMID:Morphine enhances interleukin-12 and the production of other pro-inflammatory cytokines in mouse peritoneal macrophages. 1107 13

Gram-negative sepsis is mediated by the actions of proinflammatory genes induced in response to microbes and their products. We report that flagellin, the monomeric subunit of flagella, is a potent proinflammatory species released by Salmonella. Flagellin (1 microgram/ml) induces IkappaBalpha degradation, NF-kappaB nuclear translocation, and inducible NO synthase expression in cultured intestinal epithelial cells (IEC). Aflagellic Salmonella mutants do not induce NF-kappaB activation or NO production by cultured IEC. Antiserum to flagellin blocks NO production in IEC induced by medium conditioned by a variety of motile Gram-negative enteric pathogens (Escherichia coli, Salmonella muenchen, Serratia marcescens, Proteus mirabilis, and Proteus vulgaris). Flagellin, when injected systemically (approximately 10 microgram/mouse), induces systemic inflammation characterized by the systemic expression of a range of proinflammatory cytokines and chemokines and of inducible NO synthase. At higher doses (approximately 300 microgram/mouse), flagellin induces shock, characterized by hypotension, reduced vascular contractility in mice, and death. The effects of flagellin do not diminish in C3H/HeJ LPS-resistant mice, indicating that the Toll-like receptor-4 receptor is not involved in flagellin's actions. In LPS-resistant mice, i.p. injection of S. dublin flagellin or medium conditioned by wild-type S. dublin induces serum IFN-gamma and TNF-alpha, whereas medium conditioned by aflagellic mutants has no effect. Flagellin can be detected in the blood of rats with septic shock induced by live bacteria at approximately 1 microg/ml. We propose that flagellin released by Gram-negative pathogens may contribute to the inflammatory response by an LPS- and Toll-like receptor-4-independent pathway.
 ...
PMID:Flagellin, a novel mediator of Salmonella-induced epithelial activation and systemic inflammation: I kappa B alpha degradation, induction of nitric oxide synthase, induction of proinflammatory mediators, and cardiovascular dysfunction. 1114 8

Toll-like receptor (TLR) 4 has been identified as the primary receptor for enteric LPS, whereas TLR2 has been implicated as the receptor for Gram-positive and fungal cell wall components and for bacterial, mycobacterial, and spirochetal lipoproteins. Vascular endothelial cell (EC) activation or injury by microbial cell wall components such as LPS is of critical importance in the development of sepsis and septic shock. We have previously shown that EC express predominantly TLR4, and have very little TLR2. These cells respond vigorously to LPS via TLR4, but are unresponsive to lipoproteins and other TLR2 ligands. Here we show that LPS, TNF-alpha, or IFN-gamma induce TLR2 expression in both human dermal microvessel EC and HUVEC. Furthermore, LPS and IFN-gamma act synergistically to induce TLR2 expression in EC, and LPS-induced TLR2 expression is NF-kappaB dependent. LPS and IFN-gamma also up-regulate TLR4 mRNA expression in EC. These data indicate that TLR2 and TLR4 expression in ECs is regulated by inflammatory molecules such as LPS, TNF-alpha, or IFN-gamma. TLR2 and TLR4 molecules may render EC responsive to TLR2 ligands and may help to explain the synergy between LPS and lipoproteins, and between LPS and IFN-gamma, in inducing shock associated with Gram-negative sepsis.
 ...
PMID:Bacterial lipopolysaccharide and IFN-gamma induce Toll-like receptor 2 and Toll-like receptor 4 expression in human endothelial cells: role of NF-kappa B activation. 1116 Feb 51

It has been proposed that interferon-gamma (IFN) inhibits collagen synthesis in myeloproliferative disorders through an inhibitory effect on PDGF and TGF-beta. We therefore evaluated the role of IFN-gamma on bone marrow fibrosis in idiopathic myelofibrosis (IMF). After a 3-month observation period, nine patients (five female, four male), median age 64 years (range 43-72 years), received 3 x 3 mU IFN-gamma/week over 6 months and were monitored after withdrawal of IFN-gamma for further 3 months. Three out of nine patients have completed the study according to the protocol. Six patients had to be withdrawn from IFN-gamma due to the following reasons: bacterial infection (three patients), splenic infarction or deterioration of splenomegaly (one patient, each) and refusal to continue IFN-gamma (one patient). Results from seven patients treated for at least 8 weeks were considered measurable. Leukopenia, initially present in one of the evaluated patients, deteriorated during IFN-gamma treatment. This patient died during the observation period shortly after withdrawal of the therapy as a result of septicemia. Transfusion-dependent anemia, initially observed in two of the evaluated patients, deteriorated during the IFN-gamma treatment. Bone marrow fibrosis increased in three patients, whereas it remained unchanged in another and improved in a further patient. Splenomegaly improved in two patients but deteriorated markedly in one. Taking these observations together, four patients had disease progression during IFN-gamma treatment, two had stable disease and one could be qualified as a partial responder. According to these data IFN-gamma cannot be considered as a treatment option for patients with IMF.
 ...
PMID:Ineffectiveness of interferon-gamma in the treatment of idiopathic myelofibrosis: a pilot study. 1126 29


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>