Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandin E2 (PGE2) has been implicated in the suppression of T cell IL-2 production and proliferation during burn and sepsis. The present study evaluated the potential intracellular mechanism of suppressed T cell responses by assessing the activation of p59fyn kinase in T cells from septic rats as well as the T cells incubated with PGE2. p59fyn is known to regulate T cell functions. Sepsis was induced in rats by implanting fecal pellets containing Escherichia coli (150 CFU) and Bacteroides fragilis (10(4) CFU) into the abdominal cavity. For the assessment of PGE2 role in sepsis, a group of septic rats were treated with indomethacin, which inhibits endogenous PGE2 synthesis. As assessed by immunoblotting or in vitro kinase assay, a more than 40% inhibition of p59fyn phosphorylation and kinase activity was observed in septic rat T cells compared with the T cells from sterile or control rats. A similar inhibition in p59fyn phosphorylation and kinase activity was observed in PGE2-treated T cells compared with the T cells incubated in the absence of PGE2. The septic-related suppression in p59fyn phosphorylation and kinase activity in T cells was prevented in rats treated with indomethacin. We observed that the inhibition in p59fyn activation in septic or PGE2-treated T cells was due primarily to a suppression in p59fyn phosphorylation and not due to alterations in p59fyn protein expression. These findings suggest that PGE2 released during sepsis could contribute to the sepsis-related suppression in T cell proliferation by attenuating p59fyn phosphorylation and its kinase activity.
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PMID:Prostaglandin E2 modulation of p59fyn tyrosine kinase in T lymphocytes during sepsis. 955 31

The objective of the investigation was to evaluate the possible use of selected cytokines and cytokine receptors in the early diagnosis of postoperative intraabdominal sepsis. The investigation was focused on the dynamics of plasma levels of tumour necrotizing factor-alfa (TNFalfa), interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, soluble receptors IL-2 and IL-6 (sIL-2R and sIL-6R) and the receptor antagonist IL-1 (IL-1ra). The investigated parameters were tested on model operations (resection of large bowel and resection of pancreas). These two groups were compared with values recorded in patients with sepsis and with healthy subjects. Based on the assembled results the authors recommend to use for postoperative investigations the first 48 hours and to follow up the following parameters: IL-6, IL-ra or sIL-2R. During the first 48 hours these indicators differentiate sufficiently specifically incipient sepsis from an uncomplicated postoperative condition. During the subsequent period, i.e. more than 48 hours after surgery, it is useful to include in the examination pattern also some acute stage proteins (C reactive protein, alfa1-antitrypsin and haptalobin) which differentiate sepsis between the 3rd and 5th day after surgery.
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PMID:[The significance of cytokines in the early diagnosis of postoperative intraabdominal sepsis]. 965 57

Studies indicate that lymphoid tissue (e.g., thymus, bone marrow, and Peyer's patches) shows evidence of increase apoptosis (Ao, a form of nonnecrotic cell death) during sepsis. However, it is not known if mucosal lymphoid tissue, such as lamina propria (LP), also shows evidence of increased Ao and if so, is this associated with functional changes, i.e., cytokine gene expression in the LP. To examine this, male C3H/HeN mice were subjected to cecal ligation and puncture (CLP) and lamina propria mononuclear cells (LPMC) were harvested at 4 h (early sepsis) or 24 h (late sepsis). Alterations in the cell phenotype as well as Ao (Tunel assay) were determined by three-color flow cytometry. Cytokine gene expression was assessed by multiprobe RNase protection assay. Sham LPMC preparations were found to be 34.4 +/- 2.4% B220(+) (B-cells), while 12.4 +/- 2.1% were CD8(+) (cytotoxic T-cells), 22.0 +/- 0.8% were CD4(+) (helper T-cells), and 6.4 +/- 0.7% were F4/80(+) (macrophages). The frequency of B220(+) (9%* upward arrow) and CD8 (6%* upward arrow) populations increased markedly at 4 h after CLP; however, this increase was not seen at 24 h. The percentage of Ao+ in CD8(+), B220(+), and F4/80(+) cells increased markedly at both 4 and 24 h. CD4(+) cells showed a marked increase in Ao only at 24 h after CLP. When LPMC mRNA expression was examined, a significant increase in IL-2, -10, and -15 gene expression was observed only at 24 h but not 4 h after CLP. Thus, the early phenotypic changes associated with increased Ao may be a reflection of localized immune cell activation in early sepsis contributing to the increased cytokine gene expression seen in late sepsis. This localized activation may contribute to gastrointestinal inflammation and/or immune dysfunction in sepsis.
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PMID:Sepsis induces increased apoptosis in lamina propria mononuclear cells which is associated with altered cytokine gene expression. 969 35

A 3-yr-old female patient exhibited interleukin 12 (IL-12) deficiency that was associated with recurrent episodes of pneumococcal pneumonia with sepsis and other infections in the absence of fevers. The patient's peripheral blood mononuclear cells (PBMCs) exhibited normal proliferative responses to antigens. Immune responses, including in vivo production of antibodies to diphtheria, tetanus, or pneumococcal antigens, were normal. Ig levels and B cell and T cell phenotypes were also normal. In contrast, IL-12 p70 heterodimer production was undetectable by using supernatants of the patient's stimulated PBMCs when compared with control cells treated similarly. Although present, interferon gamma (IFN-gamma) was reduced. The addition of recombinant IFN-gamma to control cells enhanced the production of IL-12 by up to sixfold. By contrast, IL-12 was undetectable in supernatants of the patient's cells in the presence of recombinant IFN-gamma. IL-12 p40 subunit mRNA by using the patient's PBMCs after stimulation with Staphylococcus aureus Cowan strain 1 or lipopolysaccharide was also undetectable by reverse transcription-PCR when compared with control cells. Production of IL-2, IL-6, tumor necrosis factor alpha, or IFN-gamma of the patient's PBMCs after appropriate stimulation was observed. This patient has either a defect in Staphylococcus aureus Cowan strain 1-lipopolysaccharide- or staphylococcal enterotoxin A-induced signaling pathways for the activation of IL-12 p40 gene expression, or an abnormality in the IL-12 p40 gene itself.
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PMID:Interleukin 12 deficiency associated with recurrent infections. 978 52

Leukocytes activated by endotoxin or enterotoxins release proinflammatory cytokines, thereby contributing to the cascade of events leading to septic shock. In the present studies, we analyzed the effects of in vivo administration of a soluble immunomodulator, beta-(1,6)-branched beta-(1,3)-glucan (soluble beta-glucan), on toxin-stimulated cytokine production in monocytes and lymphocytes isolated from treated mice. In vitro stimulation of lymphocytes isolated from soluble beta-glucan-treated mice with lipopolysaccharide (LPS) resulted in enhanced production of interleukin-6 (IL-6) and suppressed production of tumor necrosis factor alpha (TNF-alpha), while stimulation of these cells with staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin 1 (TSST-1) resulted in enhanced production of gamma interferon (IFN-gamma) and suppressed production of IL-2 and TNF-alpha compared to that in cells isolated from untreated mice. In vitro stimulation of monocytes isolated from soluble beta-glucan-treated mice with LPS also resulted in suppressed TNF-alpha production, while stimulation of these cells with SEB or TSST-1 resulted in suppressed IL-6 and TNF-alpha production compared to that in cells isolated from untreated mice. Thus, the overall cytokine pattern of leukocytes from soluble beta-glucan-treated mice reflects suppressed production of proinflammatory cytokines, especially TNF-alpha. Taken together, our results suggest that treatment with soluble beta-glucan can modulate the induction cytokines during sepsis, resulting in an overall decrease in host mortality.
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PMID:Modulation of endotoxin- and enterotoxin-induced cytokine release by in vivo treatment with beta-(1,6)-branched beta-(1,3)-glucan. 986 22

Emergent or elective surgical procedures may be complicated by sepsis, resulting in critical illness that can lead to organ failure and death. The opioid drug, morphine is widely used to alleviate pain in post-surgical patients; however, it is well documented that chronic treatment of mice with morphine affects the proliferation, differentiation and function of immune cells. Thus, morphine might be expected to exacerbate the effects of sepsis, which also compromises the immune system. To test this notion, we investigated the effect on several immune functions of a clinical dose of morphine (4 mg/kg) superimposed upon a lipopolysaccharide (LPS)-induced infection model. Our results show that this relatively low dose of morphine, though generally having no effects on immune parameters by itself, significantly augmented LPS responses. A clinical dose of morphine (4 mg/kg body weight) superimposed upon an animal model of sepsis resulted in a significant increase in mortality at 48 h. In the absence of the drug, most septic animals died after 96 h. Phenotypic responses such as, decreased thymic cellularity, compromised mitogenic response and inhibition of IL-2 synthesis that are evident at 48-72 h after LPS injection appear as early as 24 h in animals that receive morphine in addition to LPS. In addition, our results show that in T cells there is a shift from TH1 type cytokine elaboration to a TH2 type cytokine elaboration in animals that receive both LPS and morphine.
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PMID:Morphine synergizes with lipopolysaccharide in a chronic endotoxemia model. 1022 20

The present study ascertained the role of PGE2 in sepsis associated modulation of IL-2 and IL-10 production by T cells. Sepsis was induced in 225-250 g male rats (Sprague Dawley) by implanting fecal pellets containing Escherichia coli (100-150 CFU) and Bacteroides fragilis (10(4) CFU) into the abdominal cavity. Animals implanted with fecal pellets without the bacteria were designated as sterile. For the assessment of PGE2 role in sepsis, a group of septic and sterile rats were pretreated with indomethacin to inhibit endogenous PGE2 synthesis. Splenic T cells were obtained 48 h after septic or sterile implantations, and their IL-2 and IL-10 production was measured. A significant suppression in the levels of IL-2 production and mRNA expression was observed in T cells from septic rats compared with the T cells from sterile and control rats. IL-10 protein and mRNA expression was found to be significantly higher in septic rat T cell compared to sterile and control rat T cells. Although, treatment of animals with indomethacin significantly prevented the sepsis-related suppression of IL-2 production, such treatment of animals was associated with a further upregulation of IL-10 production. These data suggest that although PGE2 released during sepsis can cause T cell IL-2 down-regulation, it may not mediate the T cell IL-10 upregulation. The IL-2 down-regulation may not be an effect of IL-10 upregulation.
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PMID:Prostaglandin E2 down-regulation of T cell IL-2 production is independent of IL-10 during gram-negative sepsis. 1023 94

Procalcitonin (PCT), the precursor of calcitonin, was recently put forward as a diagnostic marker of systemic bacterial infection and sepsis. The major PCT production site in sepsis still remains unclear. Because of a certain association between increased levels of PCT and leukocyte-derived cytokines during sepsis, we assessed the possible expression of PCT in human peripheral blood mononuclear cells (PBMCs) and the modulation of PCT by lipopolysaccharides (LPS) and various sepsis-related cytokines by reverse transcriptase-polymerase chain reaction (RT-PCR) by using a novel primer set and flow cytometric analysis with intracellular staining with antibodies to the PCT components calcitonin and katacalcin. RT-PCR and flow cytometric analysis demonstrated that PBMCs express PCT both on mRNA and on protein levels. LPS and various proinflammatory cytokines (interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), IL-2) had pronounced stimulatory effects on the expression of PCT mRNA. Under identical experimental conditions the anti-inflammatory cytokine IL-10 had no effect on the expression of mRNA for PCT. Flow cytometric analysis demonstrated increased intracellular amounts of PCT components after LPS stimulation. Thus we demonstrate for the first time that PCT is expressed in PBMCs. This expression is modulated by bacterial LPS and sepsis-related cytokines. Therefore PBMCs may be among the sources of elevated PCT levels in patients with sepsis.
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PMID:Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro. 1040 59

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.
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PMID:[Immune paralysis of T-lymphocytes and monocytes in postoperative abdominal sepsis. Correlation of immune function with survival]. 1073 84

Our objectives were to study the value of different proteins in the serum and ascitic fluid and assess their potential in discriminating between malignant and nonmalignant ascites in a model that could be developed to aid clinical diagnosis. In all, 57 different measurements (30 in serum and 27 in ascitic fluid) including erythrocyte sedimentation rate, number of white blood cells, cytokines, interleukin-1a (IL-1a), IL-1b, IL-2, IL-6, IL-8, tumor necrosis factor-alpha, immunoglobulins (IgG, IgA, IgM), complement factors C3 and C4, acute-phase proteins such as alpha1-acid glycoprotein, alpha2-macroglobulin, alpha1-antitrypsin, haptoglobin, C-reactive protein, ferritin, ceruloplasmin and transferin, were performed in 61 patients with ascites (25 with malignant exudates, 13 with nonmalignant exudates, and 23 with transudates). Patients with sepsis were excluded. Correlation tests and one-way ANOVAs were used for comparisons between different groups. Discriminant analyses were used to assess the significance of each parameter in the differentiation process. Correct classification of 100% of cases required the use of all 57 ascitic fluid measurements in the model, which was not considered practical in clinical diagnosis. Discriminant analysis showed that five ascitic fluid measurements-total protein, LDH, TNF-alpha, C4, and haptoglobin-were sufficient for a model to correctly classify 89% of cases. Cross-validation showed that 70% of unknown cases were correctly classified using this model. In conclusion, we have shown that five easily taken protein measurements in the ascitic fluid can differentiate to a large extent between cases with ascites and have proposed a relatively simple statistical model with these parameters that could be developed to be extremely useful in the clinical setting.
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PMID:Discrimination between malignant and nonmalignant ascites using serum and ascitic fluid proteins in a multivariate analysis model. 1074 24


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