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)

Leptin, the ob gene product, has been proposed as a mediator of inflammatory cytokine-dependent decreased food intake and cachexia in rodents. In humans, leptin serum levels increase after administration of tumor necrosis factor-alpha (TNF-alpha) or interleukin-2 or during septicemia. However, the effect of human chronic inflammatory disease on serum leptin is unknown. We therefore determined the serum leptin level (radioimmunoassay), body mass index (BMI), percent body fat ([%BF] bioelectrical impedance analysis), and disease activity (Disease Activity Score [DAS]) in 58 patients with rheumatoid arthritis (RA) and 16 controls. The BMI, %BF, serum leptin, and ratio of leptin to %BF (leptin/%BF) did not differ significantly in 25 patients with moderate RA activity (DAS, 3.6 +/- 0.5), 33 patients with low RA activity (DAS, 1.8 +/- 0.5), and controls. A positive correlation for serum leptin and %BF was detected in all groups. Our data indicate that in RA, a human chronic cytokine-mediated inflammatory disease, the serum leptin level is directly related to %BF but not to disease activity.
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PMID:Leptin serum levels are not correlated with disease activity in patients with rheumatoid arthritis. 1038 Nov 49

When compared to controls (n = 30), human immunodeficiency virus type-1 (HIV-1)-positive individuals, either asymptomatic (n = 10) or diagnosed with acquired immunodeficiency syndrome (AIDS) (n = 10), showed a statistically significant decrease in the percentage and absolute number of CD4 ( + ) T-lymphocyte cells (flow cytometry, Becton Dickinson FACScan; mean +/- SD of 42.6 +/- 6.9 and 948.5 +/- 393.3, 19.5 +/- 8.7 and 269.8 +/- 174.3, 4.6 +/- 4.1 and 60.1 +/- 134.3, respectively; Student's t- test, p < 0.05). However, this decrease was less marked in asymptomatic patients; in fact, the percentage and number of the above cells in this group of subjects was significantly higher than in the AIDS patients (Student's t-test, p < 0.05). However, we failed to find significant differences in the percentage of natural killer cells (NKCs; CD15 ( + ) CD56 ( + ) ) between the HIV-1-infected asymptomatic or AIDS groups of patients, or when compared with the controls (mean +/- SD of 10.4% +/- 9.4%, 14.3% +/- 9.7%, and 14.8% +/- 6.4%, respectively). Whereas either group of patients had a lower number of NKCs per microliter than the control group (mean +/- SD of 137.8 +/- 87.6, 91.1 +/- 98.3, and 331. 5 +/- 266.5, respectively), this decrease only reached statistical significance for the AIDS patients (Student's t-test, p < 0.05). Healthy controls showed statistically significantly higher NKC activity than either the HIV-1-infected asymptomatic or AIDS group of patients (K-562 target cell; mean +/- SD and range values as percentage of specific lysis of 19.1% +/- 15.6% and 2.4%-58.2%, 3.4% +/- 3.2% and less than 0.1% [non-detectable]-10.3%, and 6.4% +/- 5. 5% and less than 0.1%-19.5%, respectively; Student's t-test, p < 0. 05). Challenge of samples from the control group with either interleukin-2, alpha-interferon, or with a mixture of the calcium ionophore A23187 (Io) plus the 12-O-tetradecanoylphorbol-13-acetate ester (TPA) resulted in every case in a statistically significant increase in NKC lytic function (mean +/- SD and range values as percentage of specific lysis of 19.1% +/- 15.6% and 2.4%-58.2%, 27. 6% +/- 17.4% and less than 0.1%-56.0%, 32.1% +/- 20.9% and 2.1%-76. 4%, and 62.6% +/- 24.0% and 16.7%-95.0%, respectively; Student's t-test, p < 0.05). A similar challenge for samples from the HIV-1-positive subjects, either asymptomatic or with AIDS, resulted in most cases in an enhanced NKC activity; however, this increase in NKC lytic function reached statistical significance only for the group of Io + TPA-incubated samples (Student's t-test, p < 0.05). These results indicate that control or patient baseline NKC activity, and the response of this cellular immune function to a challenge with different immunomodulators, are phenotype-independent. They also suggest an association between HIV-1 infection and alterations in the initial mechanisms responsible for NKC activation; a similar general explanation has been suggested to account for the abnormal NKC lytic function observed in various severe pathological conditions, e.g., extensive burns, polytrauma, and sepsis. Understanding the molecular mechanism involved in regulating initial NKC activation could provide the rational basis for the design of newer pharmacological strategies to treat these conditions.
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PMID:Enhancement of natural killer cell activity in HIV-1-infected subjects by a mixture of the calcium ionophore A23187 and the phorbol ester TPA: lack of response to a similar challenge with interleukin-2 or alpha-interferon. 1042 40

Recent studies suggest that increased lymphocyte apoptosis (Ao) detected in peripheral blood T cells from burn patients appears to contribute to decreased lymphocyte immunoresponsiveness. However, while it is known that sepsis induces a marked depression in the splenocyte immune response (i.e. decreased interleukin-2, interferon-gamma production and proliferation) in response to the T-cell mitogen concanavalin A (Con A), it is unknown whether this depression is associated with an increase in inducible Ao and if so, which mediators control this process. To assess this, splenocytes were harvested from mice at 24 hr (a period associated with decreased Con A response) after the onset of polymicrobial sepsis [caecal ligation and puncture (CLP)] or sham-CLP (Sham) and then stimulated with 2.5 microg Con A/ml (24 hr). Septic mouse splenocytes stimulated with Con A, while not showing a change in their phenotypic make-up, did exhibit a marked increase in the percentage of splenocyte that were Ao+ which was associated with altered cytokine release. This appears to be due to an increase in the percentage of Ao+ cells in the CD4+ CD8- population and was associated with enhanced Fas antigen expression as well as an increase in mRNA for the Fas-FasL gene family. To determine if the changes in Ao are due to either endotoxin (a product of Gram-negative bacteria seen in CLP mice) or the expression of Fas ligand (FasL; a mediator of activation-induced lymphocyte Ao), a second set of studies examining Con A-inducible Ao was performed with splenocytes harvested from septic endotoxin-tolerant C3H/HeJ and the FasL-deficient C3H/HeJ-Fasl gld mice. The results show that increased splenocyte Ao detected following CLP is due to a FasL-mediated process and not to endotoxin. Thus the inadvertent up-regulation of FasL-mediated splenocyte Ao may contribute to the depression of splenocyte immune responses seen during polymicrobial sepsis.
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PMID:Increased inducible apoptosis in CD4+ T lymphocytes during polymicrobial sepsis is mediated by Fas ligand and not endotoxin. 1044 13

Renal dysfunction is a frequently encountered adverse event following treatment with high-dose interleukin-2 (IL-2). Information about parameters predicting the severity of IL-2-associated renal function abnormalities is limited. In this study the role of possible risk factors in the development of high-dose IL-2-associated acute and long-term renal dysfunction was investigated. A total of 72 patients, who were treated with a regimen consisting of IL-2 (18 MIU m(-2) day(-1) by continuous infusion), interferon alpha (IFNalpha; 5 MIU m(-2) day(-1), intramuscularly) and lymphokine-activated killer (LAK) lymphocytes, were analysed. Serum creatinine measurements were performed daily during treatment, weekly between courses and monthly during follow-up. Pre-and posttreatment 24-h urine samples were collected for calculation of creatinine clearances. Renal dysfunction was observed in 97% of patients. Grade 1 dysfunction (according to WHO criteria) was observed in 20 patients (28%), grade 2 in 37 (51%), grade 3 in 13 (14%) and grade 4 in 0 (0%). Renal dysfunction was reversible in more than 90% of patients. Only 6 patients (8%) suffered a certain amount of permanent function loss. More severe acute renal dysfunction occurred in patients who were experiencing hypertension prior to treatment, those who suffered sepsis during treatment and in men than in women. Sepsis was also associated with irreversible function loss. Other variables such as age, performance status, diabetes mellitus, interval between nephrectomy and start of IL-2 therapy and hypotension during treatment were not important. In conclusion, with high-dose IL-2, renal dysfunction develops in almost every patient and such abnormalities are mostly reversible. Predictors for severe acute renal dysfunction are pre-existing hypertension, sepsis and sex. A septic episode also carries a risk of permanent damage.
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PMID:The role of possible risk factors for acute and late renal dysfunction after high-dose interleukin-2, interferon alpha and lymphokine-activated killer cells. 1047 8

Ex vivo production of interleukin-2 (IL-2), IL-4, IL-5, and IL-10 by peripheral blood mononuclear cells (PBMC) was studied in 13 septic patients with infectious systemic inflammatory response syndrome (SIRS) and 13 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) (noninfectious SIRS). We have investigated the levels of cytokines after activation by either concanavalin A (ConA), phytohemagglutinin (PHA), or anti-CD3 antibodies. In whole blood assays, ConA-induced IL-10 was significantly reduced in both groups of patients compared with healthy controls. In sepsis patients, IL-2, IL-5, and IL-10 productions by isolated PBMC were diminished on ConA-induced activation but not in response to PHA and anti-CD3; in CPB patients, only anti-CD3-induced IL-10 production was significantly reduced. Our data indicate that subtle modifications of the reactivity of circulating cells occur during infectious and noninfectious SIRS. Production of both Th1 and Th2 cytokines can be down-regulated; however, the nature of the SIRS, of the cell population, and of the activator may influence the observation.
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PMID:Ex vivo T-lymphocyte derived cytokine production in SIRS patients is influenced by experimental procedures. 1071 72

A novel approach to the treatment of surgical sepsis has been tried: cytokine-based immunotherapy. Human recombinant interleukin-2 (IL-2) and a mixture of native cytokines obtained by arteriovenous perfusion of xenospleen were used as a source of proinflammatory cytokines. Extracorporeal immunotherapy of 62 patients with surgical sepsis with mononuclear cells treated by autologous IL-2 resulted in a significant decrease of endotoxicosis and effective immunocorrection. Cytokine-based immunotherapy notably decreased the mortality of patients with generalized surgical infection--to 14.6%, which was lower than the expected mortality (35%) and the mortality in the control group (34.5%).
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PMID:[Cytokines in the treatment of a generalized surgical infection]. 1083 32

Nutritional intervention with omega-3 fatty acids during trauma and infection has been shown to improve the clinical outcome of patients and the survival rate in laboratory animals. This study evaluated the effects of parenteral administration of lipid emulsions containing fish oil (FO) or soybean oil (SBO) on survival and T-lymphocyte response during sepsis. Male Sprague-Dawley rats (250-275 g) were prepared for parenteral feeding 4 d before inducing sepsis by cecal ligation and puncture (CLP). Standard resuscitation was provided with normal saline. Thirty minutes after completing CLP, sham control or CLP rats were infused continuously with saline or a parenteral diet containing SBO or a 1:1 FO:SBO emulsion. The survival rate was significantly improved in rats receiving the FO-supplemented diet, with 50% alive by 120 h in comparison with the saline-infused, chow-fed rats (0% alive by 120 h) or the SBO-fed rats (12% alive at 120 h). The T-lymphocyte response was evaluated at 24 h after CLP. Sepsis led to a decline in lymphocyte proliferation in rats infused with saline or the SBO emulsion, which was associated with a greater release of splenocyte interleukin-10, transforming growth factor-beta and prostaglandin E2. Administering the 1:1 FO:SBO parenteral diet during sepsis improved the survival rate and prevented the sepsis-induced suppression of lymphocyte proliferation and interleukin-2 release. The FO effect on lymphocyte function was associated with decreased splenocyte release of transforming growth factor-beta and prostaglandin E2.
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PMID:Parenteral supplementation with a fish-oil emulsion prolongs survival and improves rat lymphocyte function during sepsis. 1124 Mar 46

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

This retrospective study from the Italian Association of Pediatric Hematology Oncology-Bone Marrow Transplant Group (AIEOP-TMO) reports the results of consolidation with high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1). From October 1994 to July 1999, 20 patients (median age 9.9 years, range 0.11-16.2) were treated in six centers. Eighteen had de novo AML and two had secondary AML. According to BFM criteria, 10 were classified as standard- and 10 as high-risk patients, respectively. The median time from diagnosis to CR1 and from diagnosis to Auto-HSCT were 1.1 months (range 0.8-1.6) and 4.3 months (range 3.1-6.2), respectively. Purging with either mafosfamide (three) or in vivo interleukin-2 (four) was performed in seven of 20 patients. Melphalan was administered at a dosage of 150-220 mg/m(2) (median 180). Median total number of nucleated cells infused was 2.5 x 10(8)/kg (range 1.1-8.9). The myeloablative regimen was well tolerated with no toxic death, veno-occlusive disease or life-threatening complications. All patients had hematopoietic recovery in a median time of 27 days for neutrophils and 44 days for platelets. Eight of 20 patients relapsed after a median time of 7.2 months from transplant (range 5.7-15.9). Six of them died (five of progression of disease and one of sepsis) while the remaining two patients are alive in CR2. The 3-year cumulative probability of survival and event-free-survival (EFS) is 62% and 56%, respectively. This study showed that in pediatric patients with AML consolidation of CR1 with high-dose melphalan allows survival and EFS to be obtained comparable to other auto-HSCT or chemotherapy published series with a potential sparing effect both on duration of treatment (with respect to chemotherapy) and on long-term side-effects (with respect to auto-HSCT with TBI or busulfan containing regimens).
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PMID:High-dose melphalan with autologous hematopoietic stem cell transplantation for acute myeloid leukemia: results of a retrospective analysis of the Italian Pediatric Group for Bone Marrow Transplantation. 1150 30

The aim of this uncontrolled, prospective, clinical study was to investigate the efficacy and safety of molgramostim administration in patients with severe sepsis. The subjects were 20 critically ill, mechanically ventilated patients with severe sepsis in a university intensive care unit (ICU). Molgramostim 300 microg s.c. was given every 12 h for 3 d. Treatment for severe sepsis was also administered as medically indicated. No adverse events (clinical or serum chemistry) were considered as drug related. Temperature (p = 0.334) and PaO2/FiO2 index (arterial oxygen tension/inspiratory oxygen fraction) (p = 0.178) were not significantly changed. Total leukocyte and neutrophil count increased significantly (p < 0.001) during drug administration. Simplified Acute Physiology Score II (SAPS II) was not significantly increased (p = 0.955), but there was a statistically significant decrease (p = 0.006) in Sepsis-related Organ Failure Assessment (SOFA) score. Death probability was not statistically different compared with mortality rate on day 28 and overall mortality (p = 0.238 and 0.700, respectively). There were statistically significant decreases (p < 0.01) in serum tumor necrosis factor-alpha (TNF-alpha), TNF-RII and interleukin-2 (IL-2), and an increase in TNF-RI levels between study entry and day 3. Mean ICU stay was 40.2 +/- 7.7 d. In conclusion, molgramostim administration may not affect serum chemistry and PaO2/FiO2 index, may decrease SOFA score but does not produce significant clinical benefit in terms of patients' outcome compared with death probability. It may also influence TNF-alpha, TNF-RI and TNF-RII serum complex levels. These changes may be attributed to the natural clinical course of sepsis or therapy applied.
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PMID:Safety and efficacy of molgramostim as an adjunctive therapy in critically ill patients with severe sepsis. 1275 12


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