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

We prospectively measured soluble interleukin-2 receptor levels in 56 premature infants with suspected sepsis and demonstrated significant differences between those with positive results on blood, urine, or cerebrospinal fluid cultures, and those with negative results. Soluble interleukin-2 receptor levels can be used to facilitate the diagnosis of sepsis in premature infants with negative blood culture results.
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PMID:Soluble interleukin-2 receptor as a predictor of neonatal sepsis. 877 29

To investigate the pathogenesis of liver dysfunction accompanying intra-abdominal sepsis, we used rats with cecal ligation and punctures (CLP) and examined the expression of the inflammatory cytokines IL-1-alpha, IL-1-beta, and TNF-alpha, as well as the expression of a cell adhesion molecule, ICAM-1, in the liver. We also examined the expression of Ia antigen and interleukin-2 receptor (IL-2R) on hepatic macrophages. Hepatic macrophages isolated from rats 24 hours after CLP exhibited significantly higher IL-1 and TNF activity than those from control rats. Hepatic macrophages isolated from rats 72 hours after CLP exhibited the maximal IL-1 and TNF activity. In the hepatic nonparenchymal cells, IL-1-alpha mRNA was induced 1 hour after CLP, increasing to the maximal level 3 hours after CLP, whereas IL-1-beta mRNA was induced gradually, reaching a peak 6 hours after CLP. ICAM-1 mRNA reached a peak 3 hours after CLP. Induction of TNF-alpha mRNA was not detected by the present Northern blot analysis. Seventy-two hours after CLP, the proportions of hepatic macrophages expressing Ia antigens and IL-2R were increased significantly, as revealed by the flow cytometric analysis. In conclusion, the present study showed that hepatic macrophages are in an activated state in sepsis as indicated by their increased production of inflammatory monokines and their increased expression of immunomodulatory surface molecules. Further, we demonstrated the sequential induction of the mRNA of the various inflammatory cytokines and ICAM-1. These findings strengthen the notion that these cytokines are relevant to the pathogenesis of liver injury associated with sepsis.
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PMID:Immunologic activation of hepatic macrophages in septic rats: a possible mechanism of sepsis-associated liver injury. 813 56

Sepsis, the major cause of morbidity and mortality after burn injury, is related to multiple immune derangements. Using monoclonal antibodies and two-colour flow cytometry to identify surface antigens, peripheral blood mononuclear cell (PBMC) populations were analysed and correlated with lymphocyte proliferation assays for 21 days postinjury. In addition, in vitro expression of activation antigens by mitogen-stimulated PBMCs was analysed during the time period. Twenty-nine burn patients were studied, with burn injuries ranging from 19 to 97 per cent TBSA; PBMCs from human volunteers were used for control cells. Patients received aggressive enteral nutritional support starting day 1 postburn and underwent early excision and grafting of wounds; no patients developed sepsis during the study period. The most consistent changes in PBMCs after thermal injury were decreased percentages of total T cells (CD3+), T helper/inducer cells (CD4+), and T suppressor/cytotoxic cells (CD8+); the percentages of natural killer (CD16+) cells were not altered. Expression of surface 'activation' antigens on CD4+ and CD8+ cells (HLA-DR, interleukin-2 receptor and transferrin receptor) after mitogen stimulation was significantly depressed as early as 1 day postburn. An early monocytosis was seen on day 1 postburn, but decreases were found on days 4 and 7. Monocyte expression of HLA-DR antigen was suppressed throughout the study. Lymphocyte proliferation after mitogen stimulation and the responses of lymphocytes in mixed lymphocyte culture were suppressed postburn. Neutrophil respiratory burst responses were supranormal on days 1 and 7 postburn, but the differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Temporal analysis of human leucocyte surface antigen expression and neutrophil respiratory burst activity after thermal injury. 843 16

Acute graft-versus-host disease (GVHD) is effected by donor T lymphocytes which have been stimulated by host antigens. Activated donor T lymphocytes express interleukin-2 receptor (IL-2R), which is comprised of three subunits (alpha, beta, gamma). During activation, the a IL-2R subunit (CD25) is shed from the receptor complex and can be measured in the circulation. Soluble IL-2Ralpha (sIL-2R) levels are increased in states of immune activation including GVHD, and could theoretically be used as a guide to therapy. Since IL-2Ralpha expression is an early marker of T cell activation, we investigated: (1) if an increase in sIL-2R is specific for acute GVHD; and (2) if serial sIL-2R levels can identify patients with early GVHD, prior to the onset of clinical tissue damage (effector function). Weekly sIL-2R levels were monitored in 36 patients undergoing matched related (n=23) or matched unrelated (n=13) allogeneic bone marrow transplantation (BMT). There was no significant difference in sIL-2R levels between matched related and matched unrelated recipients. Patients with acute GVHD (n=19, 53%) demonstrated higher sIL-2R levels, than those without during weeks 2 and 3 post-BMT (P=0.02 and 0.04, Mann-Whitney U test, two-tailed). In patients with acute GVHD, the rise in sIL-2R preceded the clinical signs of GVHD (16/19 patients). However, patients with sepsis demonstrated a trend towards higher sIL-2R levels at week 1 and significantly greater levels by week 4 (P=0.02). Furthermore, patients with veno-occlusive disease (VOD) (25%) also had significantly higher sIL-2R levels at week 2 (P=0.03). We conclude that although sIL-2R levels increase in patients with acute GVHD, similar increases are seen in patients with VOD and/or sepsis and therefore, as a single biochemical marker, we find that serial measurements of sIL-2R lacks sufficient specificity to guide GVHD therapy.
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PMID:Monitoring soluble interleukin-2 receptor levels in related and unrelated donor allogenic bone marrow transplantation. 960 99

The introduction of quadruple induction therapy after liver transplantation with the murine anti-interleukin-2 receptor (IL-2R) antibody (BT563) has decreased the incidence of serious side effects, such as tachycardia, hypertension, rash, fever and nausea since it does not lyse its target cell. To investigate the immunosuppressive efficacy of BT563, a placebo-controlled trial was performed and BT563 was added to the standard triple induction after liver transplantation. Forty consecutive recipients of primary orthotopic liver transplants (OLT) (median age 47 yr [range 18-65]) were randomized. All patients received triple immunosuppression with cyclosporine A (CyA), prednisolone (PRED) and azathioprine (AZA). In addition, 19 patients received BT563 (Biotest, Dreieich, Germany) at a dose of 10 mg/d from day 0 until day 12. The remaining 21 patients received a placebo infusion at the same days after transplantation. Minimal follow-up for all patients was 3 yr. Patient survival at 3 yr was 74% in the BT563 group and 90% in placebo group. Similar results were observed for graft survival. Two acute rejection episodes were detected in the BT563 group and 9 acute rejections (5 steroid-resistant) were observed in the placebo group (p < 0.034). The incidences of sepsis, pneumonia, cholangitis, urinary tract infections as well as cytomegalo-virus (CMV) infections were similar in both groups. Side effects of the BT563 therapy and/or post-transplant lymphoproliferative disease (PTLD) were not detected. Quadruple induction therapy with BT563 significantly reduces the incidence of rejection episodes after liver transplantation, while infectious complications and/or PTLD is not increased. Therefore, the anti-IL2 receptor antibody BT563 constitutes a safe and efficient addition to the immunosuppressive induction regimen following OLT.
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PMID:A randomized, placebo-controlled trial with anti-interleukin-2 receptor antibody for immunosuppressive induction therapy after liver transplantation. 968 24

To evaluate the change of perioperative cell mediated immunity after cardiac operation with cardiopulmonary bypass (CPB), so as to provide some information for timely prevention and treatment against postoperative immunological disorder, 40 patients were studied. By searching for the effects of CPB and anesthesia, interleukin-2 receptor (IL-2R) expression upon the surface of peripheral blood mononuclear cells (PBMC), as well as interleukin-2 (IL-2) production in vitro was traced 55 min after anesthesia, at end of CPB, on postoperative 1, 7, and 14 day versus preanesthesia control. Our data demonstrated that expression of IL-2R on PBMC was significantly suppressed in all comparing with the baseline value, meanwhile, IL-2 production in vitro also statistically dropped. However, no statistical difference was found on perioperative IL-2R expression and IL-2 synthesis in the cholecystectomy group. We conclude that postoperative immunological disorder seems to be the main factor, which could be denoted as reduced IL-2R expression on PBMC and IL-2 synthesis in vitro for sepsis, even multiple system organ failure developed after cardiac surgery.
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PMID:Changes on receptor expression and production of interleukin-2 in circulating lymphocyte population after open heart surgery. 1136 May 54

Since 1996, our standard immunosuppressive protocol for simultaneous kidney-pancreas transplantation (SKPT) has been tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids without antibody induction. When basiliximab and daclizumab, monoclonal antibodies directed against the interleukin-2 receptor (IL-2R), became available, we selectively added these agents to our standard protocol. The purpose of this prospective, open-label study was to evaluate the safety and efficacy of IL-2 receptor antagonists in SKPT. From April 1998 to August 1999, 35 SKPTS were performed. One patient with delayed graft function received Thymoglobulin and was excluded; 17 received no induction, and 17 received IL-2R antagonists (9 basiliximab, 8 daclizumab) as induction. Demographic- and transplant characteristics were similar between the two groups. At 6 months, patient survival was 88 % (15/17) in the induction arm compared to 100 % (17/17) in the no-induction arm, P = NS. The 2 causes of death were sepsis and hemolytic uremic syndrome, and both patients died with functioning grafts. Death-censored pancreas and kidney graft survival rates in the induction and the no-induction groups were 88 % vs. 100 % respectively, in both groups. The incidence of acute rejection (kidney or pancreas) at 6 months did not differ between the two groups (35 % in both groups). Biopsy proven pancreas and kidney acute rejections were 35 % vs. 24 % and 12 % vs. 12 % in the induction- and no-induction groups, respectively. The incidences of major infection and readmission did not differ between groups. TAC trough levels and mean daily doses of TAC, MMF and steroids did not differ between the two groups at 1, 3, and 6 months. The incidence of event-free survival (no death, rejection, or graft loss) at 6 months was 59 % (10/17) in the induction and 65 % (11/17) in the no-induction group. Basiliximab and daclizumab appear to be safe in SKPT. However, the preliminary results of this study do not demonstrate a significant benefit in either reducing the incidence of acute rejection or improving outcomes at 6 months. Larger studies with longer follow-up are needed to confirm these findings.
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PMID:Initial clinical experience with interleukin-2 receptor antagonist induction in combination with tacrolimus, mycophenolate mofetil and steroids in simultaneous kidney-pancreas transplantation. 1179 37

The aim of our study was to assess the effect of methylene blue infusion on plasma levels of cytokines in severe sepsis. In a prospective, randomized, double-blind, placebo-controlled study, patients received either methylene blue 0.5 mg.kg-1.h-1 (MB group, n = 15) or similar volume of isotonic saline (control group, n = 15) i.v. for 6 hours. Plasma concentrations of tumour necrosis factor-alpha, interleukin-1, interleukin-2 receptor, interleukin-6, interleukin-8 were measured by sensitive immunoassays at basal (15 min before start of the study), immediately after, and at 24 and 48 hours after methylene blue infusion. We evaluated haemodynamic parameters (mean arterial pressure, heart rate), blood gases, methaemoglobin levels, and biochemical parameters at the same time. Methylene blue administration had no significant effect on plasma cytokine levels, blood gases and biochemical parameters. When compared to placebo infusion in controls, methylene blue administration resulted in significantly higher mean arterial pressure (85 +/- 14 mmHg vs 74.1 +/- 10.3 mmHg; P < 0.01), and methaemoglobin levels (1.06 +/- 0.22% vs 0.9 +/- 0.05%; P < 0.05). Furthermore, comparison with baseline levels revealed significantly increased both mean arterial pressure (85 +/- 14 mmHg and 74.1 +/- 10.2 mmHg; P < 0.05) and methaemoglobin levels (1.06 +/- 0.22% and 0.88 +/- 0.06%; P < 0.05) in MB group. There was no difference in mortality rates between the groups. We found that methylene blue infusion did not change cytokine levels or outcome in severe sepsis. The administration of methylene blue, however, resulted in a transient increase in arterial pressure. Because of the limited size of the present study, and the short period of observation, our findings need to be confirmed by larger clinical trials of methylene blue infused in a dose-titrated manner.
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PMID:The influence of methylene blue infusion on cytokine levels during severe sepsis. 1250 May 13

Islet transplantation offers patients with type 1 diabetes mellitus freedom from long-term insulin therapy and a degree of metabolic control that is far superior to injected insulin. The hope is that near-perfect glucose control sustained over time will prevent progression of secondary diabetic complications. The selection of optimal immunosuppressive agents for islet transplantation has been a formidable challenge, given the need to overcome both autoimmune and alloimmune barriers, as well as the potential toxicity of immunosuppressive agents on transplanted islets. Early strategies relied on protocols that had proven success in solid organ transplantation and consisted of azathioprine, cyclosporine and corticosteroids. Under these protocols, fewer than 10% of patients were able to achieve insulin independence. The development of the 'Edmonton Protocol' dramatically transformed clinical outcomes in islet transplantation in recent years through the introduction of a more potent, less diabetogenic, and corticosteroid-free immunosuppressive regimen consisting of sirolimus, low-dose tacrolimus, and induction anti-interleukin-2 receptor antibody. While insulin independence rates under this protocol have been highly successful, patients must be maintained on lifelong immunosuppression. While the risk of malignancy, post-transplant lymphoma and sepsis have been low and diminishing in transplanted patients to date, fears of these complications and a host of drug-related adverse effects have precluded broader application. Patients undergoing islet transplantation today must exchange insulin for chronic immunosuppressive therapy, and therefore the procedure can only be justified in patients with very unstable forms of diabetes, or in those with another solid organ allograft who already endure the risks of immunosuppression. Advances in more specific and less toxic immunosuppressive agents together with progress in better understanding the biology of diabetes will lead to more suitable strategies to control both alloimmune and recurrent autoimmune reactions. These protocols, ultimately aimed at establishing tolerance, are an essential pre-requisite to move towards providing islet transplantation earlier in the course of the disease, including transplantation in children. This review addresses the evolution of immunosuppressive strategies in islet transplantation, and highlights some novel agents in pre-clinical development or in early clinical trials that may offer considerable promise in facilitating the induction of tolerance.
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PMID:Islet transplantation in patients with diabetes mellitus: choice of immunosuppression. 1537 74

We prospectively monitored the postmortem course of interleukin-1beta (IL-1beta), soluble interleukin-2 receptor (sIL-2R) and lipopolysaccharide binding protein (LBP) in septic and non-septic fatalities to evaluate their potential as biochemical postmortem markers of sepsis. Serum concentrations were determined by chemiluminescent immunometric assays. In both the sepsis group and the control group a postmortem increase of IL-1beta levels with the progression of time after death was observed, in both groups mainly starting from the reference concentration of healthy individuals (5 pg/ml) and with no significant differences at later time points postmortem. SIL-2R (reference limit 1,000 U/ml) was highly elevated in all individuals included in the sepsis group at all time points postmortem with statistically significant differences between the sepsis and control groups (p<0.01). An excessive postmortem decrease of sIL-2R serum levels associated with progression of time after death was observed in all cases included in the sepsis group in contrast to just 1 out of 16 control cases. LBP (reference limit <10 g/ml) was elevated in all sepsis cases whereas in the control group LBP levels were below 10 microg/ml in 88%. The postmortem time course of LBP serum concentrations showed a continuous increase in both the sepsis and control groups. We conclude that sIL-2R and LBP seem to represent appropriate diagnostic tools for the postmortem diagnosis of sepsis in forensic autopsy practice. sIL-2R serum levels above 1,000 U/ml and LBP serum levels above 10 microg/ml in peripheral venous blood obtained in the early postmortem interval can be regarded as diagnostic hints for an underlying septic condition in a deceased person.
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PMID:Serial monitoring of interleukin-1beta, soluble interleukin-2 receptor and lipopolysaccharide binding protein levels after death A comparative evaluation of potential postmortem markers of sepsis. 1537 7


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