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)

We investigated plasma levels of cytokines and endotoxin in septic shock to clarify the roles of various cytokines in this type of shock. Endotoxemia was observed in 16 of 22 septic shock patients. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta) IL-2, and IL-6 were significantly higher in septic shock than in sepsis without shock. Strong correlations were noted between TNF-alpha and IL-2 levels and between IL-1 beta and IL-6 levels. Patients with high TNF-alpha and IL-2 levels also showed endotoxemia. We defined two types of septic shock from these data, i.e., endotoxin+TNF-alpha + IL-2 shock and IL-beta + IL-6 shock. In the former type, high TNF-alpha and IL-2 levels were present before the onset of shock, and shock itself was associated with endotoxemia. The second type showed simultaneous elevation of IL-1 beta and IL-6 levels at the onset of septic shock, and endotoxin was detected in some of them. These results suggest that endotoxin and extremely high levels of TNF-alpha and IL-2, or the simultaneous elevation of IL-1 beta and IL-6, are related to the onset of septic shock.
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PMID:Two types of septic shock classified by the plasma levels of cytokines and endotoxin. 129 90

Twenty-four patients with histologically proven metastatic malignant melanoma were included in a phase II trial of recombinant IL-2 (rIL-2, RU 49637). Twenty million international units (IU)/m2/day were given by continuous intravenous infusion on days 1 to 5, 15 to 18, and 29 to 31, and then monthly for 5 days until disease progression or major intolerance developed. All patients were evaluable for response and toxicity. Toxicity was consistent with one case of myocardial ischemia, 13 cases of grade III and IV hypotension, and 15 cases of proven sepsis. There were 8 objective responses: 4 of them were of short duration as they were observed on day 31 only. An activation of the immune system was detected in all patients. It was demonstrated by an increase in lymphocyte populations, especially in activated NK cells. A tendency for higher numbers of cytotoxic cells was found in patients with objective tumor responses. These results indicate a role for rIL-2 RU 49637 in treating patients with metastatic malignant melanoma. However, further trials are required to determine its optimal dosage and schedule of administration.
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PMID:IL-2 phase II trial in metastatic melanoma: analysis of clinical and immunological parameters. 130 93

Various beneficial effects of calcium channel blockers on cell and organ function following endotoxic shock, organ ischemia, and reperfusion have been reported; however, it is not known whether these agents have any salutary or deleterious effects on immune responses after low-flow conditions. Therefore, the aim of this study was to determine (a) the effect of hemorrhage on lymphocyte IL-2, IL-3, IL-6, and IFN-gamma synthesis, and (b) whether diltiazem has any salutary or adverse effects on these parameters when administered following hemorrhage and resuscitation. To study this, C3H/HeN mice were bled to a mean blood pressure of 35 mm Hg, maintained at that level for 60 min, and resuscitated with shed blood plus twice that volume of Ringer's lactate. Immediately following resuscitation mice received either diltiazem (2400, 800, or 400 micrograms/kg body wt), or an equivalent volume of saline. The mice were sacrificed 24 hr later, splenic lymphocytes were obtained, and their capacity to produce lymphokines was assessed. The results indicated that in the vehicle-treated animals, hemorrhage significantly decreased (P less than 0.05) IL-2, IL-3, IL-6, and IFN-gamma synthesis by 82 +/- 19%, 64 +/- 28%, 71 +/- 11%, and 86 +/- 14%, respectively. However, diltiazem (400 but not 2400 micrograms/kg) treatment after hemorrhage restored lymphocyte capacity to produce IL-2, IL-3, IL-6, and IFN-gamma (P less than 0.05). Additional groups of animals were subjected to sepsis by cecal ligation and puncture 3 days following hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diltiazem restores IL-2, IL-3, IL-6, and IFN-gamma synthesis and decreases host susceptibility to sepsis following hemorrhage. 190 99

Administration of rIL-2 to BALB/c mice induces a rapid, cell-mediated response that is sufficient to protect mice from a lethal i.p. dose of Escherichia coli. Mice were protected from septic death if IL-2 was administered i.p. within 1 h after the bacterial challenge. Optimal protection was provided by treating the lethally challenged mice with rIL-2 at 1 and 5 h or 1, 5, and 10 h after the bacterial challenge and was dose-dependent (greater than or equal to 5.0 x 10(5) U/kg). Furthermore, treatment of mice with anti-IL-2R antibody abolished the protective effect induced by rIL-2 administration. These data suggest that the rIL-2-induced protection against septic death in mice is mediated by a cell type expressing a functional IL-2R. One potentially important therapeutic application of rIL-2 may be to modulate the course of sepsis once the host has been exposed to potentially lethal microbial pathogens.
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PMID:Enhanced cell-mediated protection against fatal Escherichia coli septicemia induced by treatment with recombinant IL-2. 264 49

In the burn patient, the mechanisms leading to impaired T lymphocyte activity are unclear. The capacity for T cell proliferation and the expression of Tac antigen (IL-2 receptor) was assessed during the post-burn period in patients with injuries ranging from 5-68% total body surface area. T cell-dependent (polyclonal) immunoglobulin synthesis, mixed lymphocyte reaction and Interleukin-2 production were also determined in these patients and correlated with survival. Surviving patients demonstrated a transient reduction while terminal patients exhibited a permanent reduction in the number of Tac (+) lymphocytes, unrelated to the absolute number of T cells, during the post-burn period. The reduced percentage of IL-2 receptor-expressing T cells coincided with the suppressed antibody response and reduced alloreactivity. Although the concentration of IL-2 was decreased in all patients throughout the hospitalization period, surviving patients showed a gradual increase in its production while terminal patients gradually decreased to undetectable levels. Exogenous recombinant IL-2 induced a significant enhancement of in-vitro polyclonal immunoglobulin production and blastogenesis in the mixed lymphocyte reaction in immunosuppressed patients who demonstrated up to 50% reduction in the percentage of IL-2 receptor positive cells. Thus, the reduced capacity for production of and response to IL-2 after thermal injury may lead to the immunosuppression due to a lack of T lymphocyte clonal expansion. The permanent nature of this defect in patients who died from fatal sepsis may suggest a causative relationship.
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PMID:Impairment of T cell activation in burn patients: a possible mechanism of thermal injury-induced immunosuppression. 294 98

Post-trauma immunosuppression is characterized by T-cell subpopulation changes and the presence of a low molecular weight suppressive active peptide (SAP), which suppresses T-cell blastogenesis and neutrophil chemotaxis. This study evaluated post-trauma T-cell antigens and suppressive active peptide/T-cell interactions to determine if the suppressive active peptide concentrations predictive of sepsis can cause changes in antigen expression predictive of sepsis. Human lymphocyte markers and differentiation antigens were analyzed post-trauma using flow cytometry for markers predictive of sepsis. Changes induced by purified suppressive active peptide incubated with normal human lymphocytes were similarly analyzed by flow cytometry. SAP concentrations for incubation were chosen which correlated with concentrations in patients developing clinical sepsis. Significant T-cell changes in patients who developed sepsis include: decreased total T-cells, decreased helper cells, decreased natural killer cells, increased Ia expressing mononuclear cells, increased activated T-cells, (L22) and increased IL-2 expressing cells (TAC). Suppressive active peptide can activate T-cells and cause significant increased expression of IL-2 receptors and natural killer cells. Other T-cell changes following trauma predictive of sepsis seem to occur independent of in vitro incubation with suppressive active peptides. IL-2 expressing cells are known to be more readily suppressed by the suppressive peptide. Suppressive peptide activation and subsequent inhibition of T-cells suggests a potential way to explain suppressive peptide-induced immunosuppression following trauma.
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PMID:Trauma peptide induction of lymphocyte changes predictive of sepsis. 326 88

In this brief review a description of changes in specific immune response with regard to surgical trauma is presented. The effect of anesthesia on these responses appears to be minimal. The mechanisms underlying functional abnormalities include serum inhibitory factors, suppressor monocytes, deficiency of lymphocyte-monocyte-associated fibronectin, and deficiency of IL-2 production. The factor of stress should be taken into consideration when interpreting the effect of surgery, because stress is known to influence various immune responses. The reason for various discrepancies among investigators appear to be due to technical differences, type of surgery, duration of surgery, temperature at which surgery was done (both hypothermia and hyperthermia modify the immune response), blood or plasma infusion (they appear to activate T-cells in vivo), underlying disease, and baseline immunologic status (for example, patients with malignancy with depressed preoperative immunologic status might be more or less susceptible to the effects of surgical trauma), nutritional status, drugs used, etc. Quantitative analysis should be done using monoclonal antibodies and FACS. In none of the studies published was FACS used. More detailed studies are required to understand non-T- and non-B-cell and macrophage functions in patients undergoing surgical trauma. Specific antibody responses should be studied to explain the high frequency of sepsis in the postoperative period.
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PMID:Immune response following surgical trauma. 333 6

A number of clinical studies have shown that multiple and severe trauma causes immunosuppression and increases the susceptibility to sepsis. However, because there is a close temporal relationship between trauma and hemorrhage in humans, it is difficult to dissociate the effects of tissue trauma versus hemorrhage on immunity in the clinical setting. Studies in mice have shown that simple hemorrhage per se as well as laparotomy alone produces a marked depression in cellular immunity and no difference was seen in the extent of depression at 2 h if these two insults were combined. Nonetheless, it remains unknown whether the combined model of trauma-hemorrhage produces a more protracted depression in immune function. To study this, 5 days after either sham operation, laparotomy (i.e. trauma), hemorrhage alone (35 mmHg for 1 h, followed by resuscitation), or the combination of laparotomy and hemorrhage, mice (C3H/HeN) were sacrificed, after which splenocyte and peritoneal macrophage cultures were established. The proliferative capacity of the splenocytes, as well as their ability to release IL-2 and IL-3, was markedly decreased in the trauma-hemorrhage animals but was normal in the other groups. Furthermore, the release of IL-6 by peritoneal macrophages from animals that underwent trauma-hemorrhage was also significantly depressed. These results support the concept that traumatic injury in the form of a midline laparotomy combined with hemorrhage produces a more protracted impairment in cell-mediated immunity than laparotomy or hemorrhage alone.
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PMID:Trauma-hemorrhage causes prolonged depression in cellular immunity. 749 1

Cytokine-inducible nitric oxide (NO) production has been implicated in the pathogenesis of septic shock. The present study was designed to determine which cytokines induce expression of the NO synthase gene in rat aortic vascular smooth muscle cells (VSMC) in vitro and whether NO synthase gene expression is inducible in vivo. NO synthase mRNA appeared after 4-h exposure to interleukin-1 beta (IL-1 beta), and levels continued to increase up to 24 h. Levels of NO synthase transcripts were greatest in VSMC treated with IL-1 beta (1 nM), lower in VSMC treated with Escherichia coli lipopolysaccharide (LPS; 100 micrograms/ml), and just detectable in VSMC treated with tumor necrosis factor-alpha (TNF-alpha; 1 nM). IL-1 beta, TNF-alpha, and LPS each induced NO synthase activity, assessed by release of nitrite, conversion of L-arginine to L-citrulline, and increased levels of guanosine 3',5'-cyclic monophosphate, whereas IL-2, IL-6, and interferon-gamma were ineffective. IL-1 beta was more potent and effective than TNF-alpha; however, submaximal concentrations of TNF-alpha acted synergistically with IL-1 beta to induce NO synthase gene expression and activity. Inducible NO synthase mRNA was present in aorta from rats 6 h after treatment with LPS (5 mg/kg), but not at 24 h. Synergistic activation of NO synthase gene expression in VSMC by IL-1 beta and TNF-alpha may contribute to hypotension in sepsis.
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PMID:Interleukin-1 beta and tumor necrosis factor-alpha synergistically induce NO synthase in rat vascular smooth muscle cells. 751 63

Thermal injury is associated with reduced colony-stimulating activity, which correlates with increased susceptibility to infection. To assess the effect of therapeutic administration of granulocyte-macrophage colony-stimulating factor (GM-CSF), 8-week old anaesthetized mice were subjected to either a 20 per cent body surface burn or a sham burn. Animals were subsequently treated with either vehicle or a range of doses of GM-CSF (10-1000 ng) with or without indomethacin (5 micrograms). Sepsis was induced by caecal ligation and puncture on day 10 after injury. Survival was significantly better in animals treated with 200 ng GM-CSF on days 5-9 after the burn. Concanavalin A-stimulated T cell proliferation and interleukin (IL) 2 production were significantly depressed after burn injury. In vivo therapy with 200 ng GM-CSF, however, led to a significant improvement in both of these parameters of T cell function. These data suggest that GM-CSF has a potential therapeutic role in the prevention of death from burn sepsis and appears to act, at least in part, by restoring defective T cell proliferation and IL-2 production.
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PMID:Granulocyte-macrophage colony-stimulating factor modulates immune function and improves survival after experimental thermal injury. 762 8


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