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

Interleukin-2 (IL-2) is secreted during the immune response to trauma, sepsis, and transplant rejection. Its role in the development of the metabolic abnormalities observed in these circumstances is not well defined. We studied the clinical, hormonal, and metabolic response to a 5-day IL-2 infusion (3 x 10(6) U/m2/day) of nine patients with metastatic renal carcinoma. IL-2 induced systemic manifestations after a latent period of 4 h (fever, tachycardia) or 8 h (hypotension). These manifestations persisted until the end of the infusion. Insulin levels were not modified. Among the stress hormones, cortisol increased at the onset of fever and tachycardia, whereas the rise in catecholamines occurred later (24 h) and appeared more as a response to the development of hypotension. The only metabolic effects observed were a late (third day) rise of lactate and a late and transient (third to fourth day) decrease of glycerol and nonesterified fatty acids. These metabolic modifications were temporally related to the development of hypotension and result more likely from low tissue perfusion rather than from a direct or hormone-mediated effect of IL-2.
 ...
PMID:Hormonal and metabolic effects of chronic interleukin-2 infusion in cancer patients. 234 64

During a 15-month period, 92 patients undergoing 129 treatment episodes of immunotherapy with interleukin-2 (IL-2) alone or with immune cells underwent insertion of central venous catheters (CVCs) in the Surgery Branch, National Cancer Institute. Before each catheter insertion patients were prospectively randomized into one of three treatment groups; therapy with intravenous (IV) placebo using D5W, IV oxacillin, or change of the catheter to a new site every 72 hours. The mean duration of catheterization was 3.8 +/- 1.1 days. No patient in the oxacillin arm developed catheter-related sepsis, while eight patients in the control arms (five, line change, three, placebo) developed catheter-related sepsis (P2 = .050). Seven episodes of catheter-related sepsis were due to Staphylococcus aureus and one was due to Staphylococcus epidermidis. Catheter colonization was reduced significantly in the oxacillin arm versus control arms (P = .0001). Staphylococcus aureus, Staphylococcus epidermidis, and other coagulase-negative Staphylococci were sensitive to oxacillin in 89%, 60%, and 50% of cultures, respectively. No evidence of bacterial overgrowth, candida colonization, or candidemia was observed in these patients. Thus this trial demonstrates that treatment with prophylactic oxacillin can decrease the incidence of catheter-related sepsis in patients undergoing immunotherapy with interleukin-2 (IL-2). To our knowledge this is the first prospective randomized trial to evaluate the prophylactic use of systemic antibiotics in the prophylaxis of CVC sepsis.
 ...
PMID:A prospective randomized trial evaluating prophylactic antibiotics to prevent triple-lumen catheter-related sepsis in patients treated with immunotherapy. 221 10

Activation of T-lymphocytes is accompanied by the release of interleukin-2 receptors (IL-2R) in a soluble form that can be measured as an index of the activation process. We performed a prospective, blinded study of the dynamic changes in soluble IL-2R levels in serum in 12 patients undergoing lung or heart-lung transplantation. The levels of soluble IL-2R were markedly elevated during episodes of rejection (geometric mean value X divided by SEM = 3,770 X divided by 1.06 versus 411 X divided by 1.08 U/ml for normal controls, p less than 0.0001). Levels of soluble IL-2R were 2,105 X divided by 1.16 U/ml with rejection episodes in single lung recipients versus 5,560 X divided by 1.30 in recipients of two lungs (p = 0.005). Soluble IL-2R levels were 1,468 X divided by 1.05 during episodes of nonbacterial infections, 1,879 X divided by 1.34 with bacterial infections, and 5,056 X divided by 1.08 with sepsis (p less than 0.001 for each category compared to normals). Levels of soluble IL-2R exceeded 6,750 U/ml only with rejection episodes and were greater than 4,100 U/ml either with rejection, clinical sepsis, or overwhelming bacterial infection. We conclude that marked elevations of soluble IL-2R are associated with rejection, intermediate elevations with either rejection or infection, and that low levels of soluble IL-2R exclude rejection.
 ...
PMID:Dynamic changes in soluble interleukin-2 receptor levels after lung or heart-lung transplantation. 250 85

Interleukin-2 (IL-2)-based immunotherapy is associated with profound reversible cholestasis and hyperbilirubinemia. We performed a nonrandomized retrospective and prospective analysis to determine the incidence, characteristics, clinical course, and nature of the IL-2-induced liver dysfunction in patients with cancer. Patients received IL-2 at a dose of 20,000 to 100,000 units (U)/kg thrice daily for up to 5 days. Fifty-one patients on adjuvant treatment protocols received a mean of 10.18 +/- 2.38 IL-2 doses and 11.67 +/- 4.16 doses were delivered to 210 patients with advanced disease during this period. Retrospective analysis of all patients receiving this therapy revealed increases in the following liver function tests expressed as median, 25th percentile, and 75th percentile (range): bilirubin (mg/dL) 4.5, 2.6, 6.5 (.4 to 38.5); alkaline phosphatase (U/L) 256, 179, 378 (56-1680); SGOT (U/L) 80, 52, 117 (18 to 483); SGPT (U/L) 91, 64, 132 (20-540); prothrombin time 13.4, 12.8, 14.5 (10.8 to 35.4); and albumin (g/dL) values decreased (trough) slightly 3.0, 2.8, 3.2 (2.3 to 3.8). Multiple regression analysis revealed several factors that were significantly associated with the increase in bilirubin when jointly considered (model P2 less than or equal to .001) including total IL-2 dosage, increase in creatinine, alkaline phosphatase, weight, and SGOT. Similar increases were noted in a prospectively evaluated group of 10 patients. A return to normal levels of bilirubin was noted within 5.6 days of stopping IL-2. Fasting serum cholylglycine increased from a mean of 32.3 +/- 1.6 to a peak of 1556.0 +/- 625.0 mg/mL. Although conventional ultrasound examinations were unrevealing, tissue ultrasound examinations revealed a mean scatterer spacing (MSS) increase compared to baseline of .10 +/- .04 (P less than .02) suggesting hepatic edema or an infiltrative process. Further, computerized hepatobiliary nuclear medicine scans revealed a delay in uptake (2.2 +/- 0.5 fold greater) and excretion (8.0 +/- 5.9 fold greater) of technetium-99m labeled disofenin. These findings support the development of profound reversible cholestasis as the primary basis for the elevated bilirubin in patients undergoing IL-2 treatment and may have implications for understanding the jaundice observed in some patients postoperatively as well as that associated with sepsis and other inflammatory disorders. Specifically, the release of IL-2 or the induction of other factors similarly induced by IL-2 may be responsible for these findings. Tissue ultrasound and computerized hepatobiliary scans provide additional noninvasive assessments of liver function and physiology.
 ...
PMID:Interleukin-2 induces profound reversible cholestasis: a detailed analysis in treated cancer patients. 258 24

The mechanism by which simple hemorrhage profoundly impairs the proliferative response of T lymphocytes to mitogen and alloantigen, produces a defect in interleukin-2 generation, and increases the susceptibility to sepsis remains unknown. Since antigen presentation (AP) by the macrophage (M phi) plays a critical role in the antigen-specific activation of T-helper cells and lymphokine production, we investigated whether the function of the M phi as an AP cell is altered following hemorrhage. C3H/HEJ mice were bled to a mean BP of 35 mm Hg, maintained at that level for 1 hr, and then resuscitated. There was no mortality with this model. Control mice were not bled but otherwise treated identically. Immediately after resuscitation the mice were sacrificed and peritoneal M phi (PM phi) as well as splenic adherent cells (SAC) were harvested. AP function was tested by coculturing different numbers of PM phi and SAC with D10.G4.1 cells (2 x 10(4) cells/well) in the presence of conalbumin (300 micrograms/ml). This T-helper cell clone proliferates upon recognition of conalbumin in the context of Iak (a M phi surface membrane glycoprotein), thus directly reflecting M phi AP capability. After 72 hr of incubation, the cultures were pulsed with [3H]thymidine and harvested. D10.G4.1 proliferations induced via AP by PM phi and SAC from hemorrhaged-resuscitated mice were 29 and 24% of control, respectively (P less than 0.05). Thus, we conclude that AP by M phi following hemorrhage is defective despite adequate resuscitation, a mechanism which could explain the state of immunosuppression and enhanced susceptibility to sepsis.
 ...
PMID:Mechanism of immunosuppression following hemorrhage: defective antigen presentation by macrophages. 273 18

Levels of T lymphocytes were measured in 20 consecutive patients, 18 men and two women, supported with ventricular assist devices or an artificial heart. Indications for support were bridge to transplantation (n = 10), postcardiotomy cardiogenic shock (n = 8), and acute myocardial infarction shock (n = 2). Control levels were from healthy volunteers not undergoing cardiac operation. Preoperatively, numbers of total lymphocytes and subclasses CD3, CD4, and CD8, as well as the interleukin-2 receptors (IL2R), were the same as controls (cells/microliters): lymphocytes, 1,940; CD3, 1,413 +/- 410; CD4, 894 +/- 318; CD8, 490 +/- 185; IL2R, 96. From implant to postoperative day 5, levels were below control values (p less than 0.001), reaching a nadir on postoperative day 2 (lymphocytes, 896 +/- 599; CD3, 489 +/- 267; CD4, 309 +/- 207; CD8, 183 +/- 107; IL2R, 43 +/- 47). Data from 10 patients (group 1) who survived (four weaned from cardiopulmonary bypass, six transplanted) were compared with those from 10 patients (group 2) who died of multiorgan failure, sepsis, or both. From preimplant through postoperative day 6, levels did not differ between groups. However, from postoperative day 7 to the last day of ventricular support (group 1, 24-90 days; group 2, 7-29 days), group 1 levels (lymphocytes, 2,364 +/- 618; CD3, 1,825 +/- 553; CD4, 1,013 +/- 187; CD8, 796 +/- 402) were significantly above (p less than 0.01) group 2 levels (lymphocytes, 1,290 +/- 463; CD3, 746 +/- 295; CD4, 534 +/- 253; CD8, 221 +/- 106). These data indicate that lymphocytes and particularly T cells 1) decrease after ventricular assist device insertion, reaching a nadir at postoperative day 2, 2) return to control values after patients whose clinical status improves, and 3) remain low in severely ill patients. T-cell depression in ventricular assist device patients is related to the severity of the patient's condition rather than the presence of the device.
 ...
PMID:T cells in ventricular assist device patients. 280 99

Sepsis and endotoxaemia are common in fulminant hepatic failure (FHF) and may contribute to multisystem disease in such patients. Tumour necrosis factor (TNF) is a probable mediator of endotoxic shock and infusion of this monokine into animals causes multi-organ failure that shares features with FHF. In patients with FHF, TNF production was increased and correlated closely with activity of interleukin-1, another cytokine that is released by monocytes/macrophages in response to infection and endotoxin and is produced in increased quantities in FHF. Interleukin-2 activity was impaired in FHF and correlated negatively with TNF production.
 ...
PMID:Enhanced tumour necrosis factor and interleukin-1 in fulminant hepatic failure. 289

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.
 ...
PMID:Impairment of T cell activation in burn patients: a possible mechanism of thermal injury-induced immunosuppression. 294 98

Sepsis is occasionally accompanied by jaundice which is marked by an intrahepatic cholestasis and scant hepatocyte necrosis. The pathogenesis is unknown. The bile fistula rat was used in this study to investigate the possibility that intrahepatic cholestasis is one of the many systemic effects of the major endogenous pyrogen, interleukin-1. The effect of acute administration of endotoxin, interleukin-2 and recombinant rat interferon gamma on biliary secretion and biliary transport mechanisms was also studied. Basal bile flow, peak bile flow and peak sodium taurocholate output were measured after 1 h in all cases, except with recombinant rat interferon gamma where the time interval was 3 h. Endotoxin significantly reduced basal and sodium taurocholate-stimulated bile flow, as well as sodium taurocholate secretion. No such effect was noted after acute administration of any of these lymphokines or chronic administration of interleukin-1. The cholestasis induced by endotoxin administration is not mediated by interleukin-1, interleukin-2 or recombinant interferon gamma.
 ...
PMID:Lymphokines and bile secretion in the rat. 295 76

Impaired immune competence leading to decreased resistance to sepsis is a major cause of death in burn patients. We have previously shown that increased mortality from a septic challenge correlated with impaired splenocyte interleukin-2 (IL-2) production and response to T cell mitogens in mice subjected to a 25% surface area scald burn. We report now that the addition of recombinant (r) IL-2 (100 U/ml) in vitro to splenocytes from burned animals restored mitogen responses to normal. Burned mice intraperitoneally received 16,000 U of rIL-2 (selected on the basis of dose-response experiments) once daily in 0.5 ml 5% dextrose (5% D) on days 1 through 6 after thermal injury and were compared with burned mice treated with only 5% D. Both groups were subjected to cecal ligation and puncture 10 days after burn; 4 days later, there were no survivors in the 5% D group, whereas 45% of the rIL-2 group remained alive (p = 0.001; Gehan statistic). We found that rIL-2 treatment at the dose selected resulted in no apparent toxicity in burned mice. Finally, splenocytes from rIL-2-treated burned mice showed improved responses to T cell mitogens in vitro compared with 5% D-treated controls. We conclude that rIL-2 therapy may have a role in the restoration of immune competence after thermal injury.
 ...
PMID:Recombinant interleukin-2 (rIL-2) improves immune response and host resistance to septic challenge in thermally injured mice. 326 Oct 49


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