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)

Background: At present, it is unclear whether in experimental endotoxemia, the pro-inflammatory response observed in healthy volunteers is followed by an anti-inflammatory response, as observed in patients with sepsis. We studied the evolution of a number of inflammatory parameters during a prolonged period (24 h) after infusion of endotoxin in healthy subjects. Methods: Six healthy male subjects received an infusion of endotoxin (4 ng/kg body weight). Blood was drawn before, and at various intervals up to and including 24 h after, endotoxin infusion. Circulating cytokine levels, leukocyte activation surface markers, plasma lactoferrin, and neopterin levels were measured, and clinical signs and symptoms were noted during a 24-h period. Monocyte and neutrophil activation after endotoxin infusion is investigated in relation to the inflammatory response. The extent of neutrophil and monocyte activation was correlated to clinical markers and blood levels of inflammatory mediators and cytokines. Results: Tumor necrosis factor-alpha appeared 30 min after infusion in the circulation, peaking (5665+/-1910 pg/ml) at 2 h. Interleukin-10 appeared 60 min after infusion, peaking (427+/-348 pg/ml) at 3 h. The expression of leukocyte activation markers increased significantly after infusion. Expression of HLA-DR on monocytes decreased significantly after 3 h (P=0.03). There was a correlation between the TNF-alpha:IL-10 ratio and the CD11b:HLA-DR ratio (P=0.03). Conclusions: During experimental human endotoxemia, an initial pro-inflammatory response is successfully compensated by an anti-inflammatory response, leading to homeostasis. This is in contrast to what happens in septic patients with compensatory anti-inflammatory response syndrome. The inflammatory balance, expressed as the cytokine pro:anti-inflammatory ratio, is reflected at a cellular level.
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PMID:Leukocyte activation and cytokine production during experimental human endotoxemia. 1074 52

Despite advances in critical care medicine, mortality from sepsis in ICU patients remains high. In response to several infectious and non-infectious stimuli, monocytes/ macrophages release a number of mediators, including cytokines, involved in the proinflammatory response that underlies sepsis. The excessive release of these mediators results in the development of whole body inflammation, and plays an important role in the pathogenesis of sepsis and septic shock. In addition, patients with sepsis also undergo an anti-inflammatory phase (the compensatory anti-inflammatory response syndrome) and at times, a mixed response with both pro-and anti-inflammatory components (the mixed antagonistic response syndrome). The initial systemic hyperinflammation is caused by production of inflammatory cytokines, especially tumour necrosis factor-a (TNF-alpha), and also interleukin-1 (IL-1), IL-6, and interferon gamma, which act synergistically with TNF-alpha in inducing shock in animal models. However, clinical trials aimed at downregulating these mediators using antibodies against endotoxin, TNF-alpha, antagonists of IL-1 or platelet activating factor have proved to be uniformly disappointing. Not only have these agents been found to have no effect, but they may also increase mortality. One of the reasons for such failure may be the lack of precise immunological monitoring during the course of sepsis. We have recently demonstrated that sepsis shows a biphasic immunological pattern during the initial and later phase: the early hyperinflammatory phase is counterbalanced by an anti-inflammatory response which may lead to a hypoinflammatory state. The latter is associated with immunodeficiency that is characterised by monocytic deactivation, so-called immunoparalysis. Interferon gamma-1 b has an immunoregulatory effect in patients with immunoparalysis during the compensatory anti-inflammatory response syndrome, not only restoring levels of HLA-DR expression but also reestablishing the ability of monocytes to secrete cytokines such as TNF-alpha. By monitoring immune status in septic patients, targeted intervention may lead to more success in immunomodulation of sepsis.
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PMID:Immunomodulatory therapies in sepsis. 1078 69

The systemic inflammatory response (SIRS) results from various types of injuries such as severe infection, trauma, ischemia-reperfusion and major surgery including cardiac surgery with cardio-pulmonary bypass. This response involves immune cell activation and a complex network of proinflammatory cytokines, which may induce multiple organ failure when uncontrolled. The monocyte plays a central role in the response to infection with the release of TNF, IL-1, and IL-12. In addition, monocytes present antigens to T lymphocytes. An optimal antigen presentation requires the expression of MHC class II HLA-DR on monocytes surface and of co-stimulatory molecules such as CD54 on monocytes and LFA-1 on lymphocytes. It has become increasingly apparent that the pro-inflammatory response is balanced by concomitant anti-inflammatory mechanisms that results in monocyte deactivation, characterized by a decrease in HLA-DR expression and the release of anti-inflammatory cytokines such as IL-10. This counterregulatory response, if prolonged or predominant, may predispose the patient to a higher risk of infection. Further studies need to be conducted to precise: 1) the intensity of depression of the surface molecule expression assessing monocyte function, such as HLA DR and CD54; 2) the level of IL-10 and IL-12 release in patients with severe sepsis; 3) the immunomodulating effects of frequently used treatments in these patients with severe sepsis and in surgical patients; 4) the time course of recovery; 5) if the monitoring of HLA-DR, CD54, IL-10 and IL-12 will better predict the clinical outcome than clinical parameters.
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PMID:Assessment of immunological status in the critically ill. 1096 15

The influence of glutamine on human immune system is multidirectional but the exact changes still remain unclear. In this study the effect of total parenteral nutrition (TPN) enriched with glutamine on some selected immunological and nutritional parameters was examined in twelve surgical patients with sepsis and malnutrition. The reason for glutamine supplementation was lack of clinical improvement after standard TPN. All patients received TPN enriched with glutamine for 10 days. Phenotypic analysis of peripheral blood mononuclear subsets (CD4, CD8, CD16, CD56, HLA-DR) were measured before, during (on days 2, 4, 6) glutamine administration and two days after (day 12) glutamine withdrawal. Simultaneously some nutritional parameters were assessed. The number and percentage of CD4, CD16, CD56 mononuclear subsets increased significantly on day 2 and stayed on the same level during observation (with exception in CD4 on day 6, 12 and CD56 on day 4). No significant differences in CD8 and HLA-DR number and percentages were observed after TPN enriched with glutamine. BIA examination revealed on days 2 and 12 significant decrease of total body water and significant increase of body cell mass, intracellular water on day 12. It was correlated with significant higher total lymphocytes count and significantly higher total protein, serum albumin, transferrin, cholesterol and CRP concentration. Results demonstrated that TPN supplemented with glutamine improved rapidly some immunological and nutritional parameters in surgical, malnutrition patients with sepsis.
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PMID:[Cellular immunity changes after total parenteral nutrition enriched with glutamine in patients with sepsis and malnutrition]. 1096 19

Monocyte phenotype, their phagocytic capacity as well as the cytokine production from 10 patients with sepsis with low interleukin-6 (IL-6) serum concentrations (<1000 pg/mL) and 8 patients with sepsis with high IL-6 (> or = 1000 pg/mL) plasma concentrations were investigated within 24 hours of fulfilling the criteria for sepsis. Monocytes from patients with high IL-6 levels had higher levels of human leukocyte antigen (HLA)-DR, HLA-ABC, CD64, and CD71, and the production of tumor necrosis factor-alpha (TNF-alpha) and IL-8, as well as the capacity of monocytes to phagocytose, was significantly elevated. Of 8 patients with high levels of plasma IL-6, 4 patients died. In contrast, all 10 patients with low plasma IL-6 concentrations survived until day 28. Patients who died had constant high IL-6 concentrations during the first 3 days, whereas IL-6 levels in patients who survived decreased by 88%. Our data indicate that IL-6 levels are a better prognostic parameter in the early phase of sepsis than the monocyte HLA-DR expression.
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PMID:Relationship between interleukin-6 plasma concentration in patients with sepsis, monocyte phenotype, monocyte phagocytic properties, and cytokine production. 1109 99

The systemic inflammatory response (SIRS) results from various types of injuries such as severe infection, trauma, ischemia-reperfusion and major surgery including cardiac surgery with cardio-pulmonary bypass. This response involves immune cell activation and a complex network of proinflammatory cytokines, which may induce multiple organ failure when uncontrolled. The monocyte plsys a central role in the response to infection with the release of TNF-alpha, IL-1 beta, and IL-12. In addition, monocytes present antigens to T lymphocytes. An optimal antigen presentation requires the expression of MHC class II HLA-DR on monocytes surface and of costimulatory molecules such as CD54 on monocytes and LFA-1 on lymphocytes. It has become increasingly apparent that the proinflammatory response is balanced by concomitant anti-inflammatory mechanisms that results in monocyte deactivation, characterized by a decrease in HLA-DR expression and the release of anti-inflammatory cytokines such as IL-10. This counterregulatory response, if prolonged or predominant, may predispose the patient to a higher risk of infection. Further studies need to be conducted to precise: i) the intensity of depression of the surface molocule expression assessing monocyte function, such as HLA DR and CD54; ii) the level of IL-10 and IL-12 release in patients with severe sepsis; iii) the immuno-modulating effects of frequently used treatments in these patients with severe sepsis and in surgical patients; iv) the time course of recovery; v) if the monitoring of HLA-DR, CD54, IL-10 and IL-12 will better predict the clinical outcome than clinical parameters.
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PMID:Assessment of immunological status in the critically ill. 1119 84

Severe sepsis and probably most prolonged critical illnesses reflect a paradox of combined increased activation and depression of the immune apparatus. The increased activation of the inflammatory response is evidenced from the increased levels of circulating proinflammatory cytokines in the blood, increased endothelial activation with increased expression of inducible nitric oxide synthase, and increased de novo CD11b expression on circulating immune effector cells, such as PMNs, monocytes and lymphocytes. However, coexisting with this proinflammatory process is a profound anti-inflammatory state characterized by increased circulating levels of anti-inflammatory species that both directly block the binding of proinflammatory stimuli to their cell surface receptors (IL-1ra, soluble TNF receptors) and also induce an anti-inflammatory state on their own (IL-10, TFG-beta). This humoral anti-inflammatory state is mirrored at the cellular levels by decreased monocyte ability to process antigen, characterized by a reduced HLA-DR expression and impaired PMN upregulation in response to clearly proinflammatory stimuli. Accordingly, severe sepsis reflects a combined pro- and anti-inflammatory state. Both the pro- and anti-inflammatory arms have protective and destructive aspects, making their modulation by treatment less predictable than if their actions were purely beneficial or detrimental.
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PMID:Sepsis: a pro- and anti-inflammatory disequilibrium syndrome. 1139 3

The plasma levels of procalcitonin (PCT) are increased in patients with severe bacterial infections. Its cellular origin and potential pathophysiological function in sepsis is, however, unclear. White blood cells have recently been described to express both PCT mRNA and protein. The aim of this study was to determine whether PCT has any influence on the surface expression of receptors, relevant in inflammation, on human whole blood leukocytes under normal and septic conditions. Venous blood from healthy donors was incubated with PCT (40 ng/ml or 1200 ng/ml) alone or in combination with lipopolysaccharide (LPS, 10 ng/ml) or peptidoglycan (PepG, 10 micrograms/ml) for 6 h. The surface expression of CD14, CD54, CD64, CD80, CD86 and HLA-DR was determined by flow cytometry. We could not detect any influence of PCT on the expression of these receptors. Further studies on potential effects on other cell types during infection seem warranted.
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PMID:Procalcitonin does not influence the surface expression of inflammatory receptors on whole blood leukocytes. 1139 89

Bacterial superantigens are believed to cause septic shock, although, because of the lack of superantigen-sensitive infection models, proof that superantigenicity underlies shock pathogenesis is lacking. This work demonstrates a clear superantigen effect in septic shock resulting from bacterial infection. Transgenic expression of human leukocyte antigen (HLA)-DQ, but not HLA-DR, specifically augments lymphocyte responses to streptococcal pyrogenic exotoxin A (SPEA). HLA-DQ transgenic mice had increased mortality after administration of SPEA or infection with Streptococcus pyogenes. Immune activation during infection was HLA-DQ transgene-dependent and was manifested by Vbeta-specific T cell repertoire changes and widespread lymphoblastic tissue infiltration. Unlike earlier models, which used toxin-induced shock, these T cell superantigen responses and lymphoblastoid changes were observed during invasive streptococcal sepsis. Lymphoid activation was undetectable in HLA-DQ mice infected with an isogenic SPEA(-) strain, which proves that a single superantigen can play a role in sepsis pathogenesis.
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PMID:Enhanced susceptibility to superantigen-associated streptococcal sepsis in human leukocyte antigen-DQ transgenic mice. 1142 13

Bacterial sepsis remains a frequent complication after liver transplantation. We previously reported the results of a pilot study that suggested that low expression of HLA-DR on monocytes is a predictive marker for the occurrence of sepsis. We have studied the value of this marker in an additional cohort of patients, and have analyzed the relation of HLA-DR expression with the use of immunosuppressive agents. 20 adult liver transplantation patients were prospectively monitored during the first 4 weeks after transplantation. All were treated according to standard protocols. The percentage of monocytes expressing HLA-DR was measured by flow cytometry. In addition, the effects of incubation of monocytes with prednisolone in vitro on the expression of HLA-DR was determined in 7 healthy volunteers. Seven patients developed bacterial sepsis after a median 15 (range 10-20) days after transplantation. HLA-DR expression was significantly lower in these patients on days 7, 14, 21, and 28 after transplantation compared with non-septic patients. The percentage of HLA-DR positive monocytes was 30% or less, 3 (1-8) days before onset of sepsis. On day 7 after transplantation, HLA-DR expression on 50% or less of monocytes had a positive predictive value for sepsis of 71%, whereas the negative predictive value was 85%. Patients who developed sepsis received significantly more prednisolone. Incubation with prednisolone in vitro lowered the expression of HLA-DR in a dose-dependent manner. We conclude that low HLA-DR expression on monocytes is a marker for a high risk of subsequent sepsis in liver transplantation patients. This high risk may be (at least partly) related to the dose of prednisolone.
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PMID:Low HLA-DR expression on peripheral blood monocytes predicts bacterial sepsis after liver transplantation: relation with prednisolone intake. 1142 84


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