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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Distinct cytokine profiles are clearly associated with and relate to the severity of several types of infections. Cytokine networks are apparent with selected human infectious diseases, such as mycobacterial infections (leprosy, tuberculosis), the parasitic infection leishmaniasis, human immunodeficiency virus (HIV) infection, and gram-negative sepsis. Cytokine profiles are determined to some extent by two functional subsets of T lymphocytes, Th1 and Th2. The Th1 cytokines (interferon gamma, interleukin-2 [IL-2], IL-12) enhance cell-mediated immunity, inhibit humoral immunity, and result in protective effect for pathogens that are removed primarily through cell-mediated immunity (Mycobacterium tuberculosis, Mycobacterium leprae, Leishmania). The Th2 cytokines (IL-4, IL-5, IL-10, IL-13) enhance humoral immunity and inhibit cell-mediated immunity, and result in protective effect for pathogens removed primarily through humoral mechanisms. Progression of HIV infection is associated with a switch from a Th1 to a Th2 profile. For sepsis, uncontrolled activation of proinflammatory cytokines (IL-1, tumor necrosis factor-alpha, interferon-gamma) may be a fundamental defect that promotes the detrimental aspects of inflammation, whereas Th2 cytokines may be beneficial in controlling inflammation. Knowledge of basic cytokine immunopharmacology, networks, and relationships with infectious processes will aid clinicians in determining treatment approaches that are likely to be effective.
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PMID:Cytokine networks with infection: mycobacterial infections, leishmaniasis, human immunodeficiency virus infection, and sepsis. 908 11

Cytokine levels during infection and sepsis have been extensively studied in the past. In contrast to the excellent data on tumour necrosis factor alpha (TNF-alpha), interleukin 8 (IL-8), and polymorphonuclear (PMN) granulocyte elastase (PMN-E) concentrations in blood, little is known about cytokine and PMN-E levels in tissue or local fluids like abdominal exudate in secondary, purulent peritonitis of man. Therefore, the authors studied perioperative intra-abdominal levels of TNF-alpha, IL-8 and PMN-E in 21 patients with severe purulent peritonitis. The average pre-operative levels of TNF-alpha were 694 +/- 239 pg/ml in exudate and 26 +/- 6 pg/ml in plasma, for IL-8 100 +/- 34 ng/ml and 0.7 +/- 0.5 ng/ml, and for PMN-E 68 +/- 14 microg/ml and 0.7 +/- 0.1 microg/ml, respectively. Standard surgical procedures reduced the intra-abdominal concentrations of cytokines and PMN-E to as low as one tenth of the pre-operative levels. Postoperatively, TNF-alpha and IL-8 levels recovered rapidly and pre-operative levels of IL-8 were reached again after 1 h and for TNF-alpha after 8 h. PMN-E concentration remained below the initial baseline within 8 h of observation. TNF-alpha concentration, but not IL-8 or PMN-E, depended on the microbiological load of the abdominal exudate (< or > 10(3) cfu/ml). There were no significant differences in the intra-abdominal or plasma levels of cytokines or PMN-E between survivors and non-survivors at any observation time.
Cytokine 1997 Apr
PMID:Perioperative pattern of peritoneal interleukin 8, tumour necrosis factor-alpha, and granulocyte elastase release in human secondary peritonitis. 911 38

Individuals with a consistently lower immune response may be more susceptible to infection but less prone to autoimmune disease or severe sepsis. The molecular mechanisms determining the low responder status are, however, unclear. We have screened 60 male donors for tumour necrosis factor (TNF) protein levels after stimulation of monocytes with lipopolysaccharide (LPS). Among these we identified three donors each that consistently had a level of less than 20% (low responders; LR) or of more than 80% (high responders; HR) of the maximum response seen in this population. Northern blot analysis of TNF mRNA after LPS stimulation revealed lower transcript levels in LR. Half life determination after actinomycin D blockade showed a similar decay rate for LR and HR and after blockade of degradation by cycloheximide treatment mRNA levels increased but LR remained lower compared to HR. These data indicate that the lower TNF mRNA levels in LR are not due to a more rapid mRNA degradation but rather a result of lower transcription. Transcripts for interleukin 6 (IL-6) were also low in LPS-stimulated monocytes of LR. Because expression of the LPS receptor CD14 was similar in LR and HR monocytes, our data suggest that differences in signal transduction account for the LR and HR phenotype.
Cytokine 1997 Mar
PMID:TNF gene expression in monocytes of low and high responder individuals. 912 9

Streptococcus pneumoniae can produce asymptomatic colonization or aggressive sepsis. We sought to differentiate the molecular mechanisms of these disparate courses. Cytokine or thrombin activation of human vascular endothelial cells and type II pneumocytes enhanced pneumococcal adherence relative to resting cells. Adherence and subsequent invasion was dramatically reduced by PAF receptor antagonists. Cells transfected with the PAF receptor gained the ability to support pneumococcal adherence. PAF or PAF receptor antagonists inhibited attachment and invasion. Adherence involved phosphorylcholine on the pneumococcal teichoic acid. Virulent pneumococci target the PAF receptor on activated human cells, a necessary step to facilitate subsequent invasion.
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PMID:PAf receptor anchors Streptococcus pneumoniae to activated human endothelial cells. 913 Nov 32

Lipopolysaccharides (LPS) of gram-negative bacteria and superantigens of gram-positive bacteria are among the main causes of sepsis and septic shock. Symptoms are initiated primarily by the release of endogenous mediators, especially cytokines. In the last few years, increasing evidence for the clinical relevance of mixed sepsis caused by coinfections with both types of bacteria has been found. Therefore, we developed an in vitro mixed sepsis model investigating the effect of different superantigen doses, in combination with different LPS concentrations, on cytokine production in human PBMCs using ELISA and RT-PCR. Low, in vivo relevant concentrations of the superantigen toxic shock syndrome toxin-1 (TSST-1) synergistically enhance LPS-induced production of interferon-gamma (IFN-gamma) interleukin-1 beta (IL-1 beta), IL-6, and IL-10, but low LPS has no comparable effect. Signal transduction studies with different inhibitors suggest that this one-way synergism is caused by an interaction between the cAMP and the PIP2 signaling pathway. Furthermore, our findings support the idea that this interaction is one important crossover point of signal transduction pathways by LPS and superantigens, which seems to be predominantly regulated by IFN-gamma and PGE-2. The identification of additional crossover points in the genesis of a mixed sepsis and their selective influence could lead to identical treatment of both gram-negative and gram-positive sepsis.
J Interferon Cytokine Res 1997 Apr
PMID:One-way synergistic effect of low superantigen concentrations on lipopolysaccharide-induced cytokine production. 914 52

Studies indicate that the liver, in particular the Kupffer cells, appear to be key contributors in the systemic inflammatory mediator response associated with shock and sepsis. Although several of these agents have been implicated as mediators of depressed immunoresponsiveness observed during sepsis, it remains unknown whether or not mediators released specifically by Kupffer cells play any significant role in producing the cellular dysfunction in distant organs. The aim of this study, therefore, was to determine whether or not acute Kupffer cell reduction before the onset of sepsis would protect splenic lymphocyte function. Kupffer cell number was reduced by prior (48 hours) treatment of mice with gadolinium chloride (GdCl2, 10 mg/kg of body weight, intravenously) or saline vehicle. Animals were then subjected to either sham-CLP (sham) or polymicrobial sepsis in the form of cecal ligation and puncture (CLP). Plasma and splenocytes were harvested at 2 or 24 hours after CLP. Splenocyte cultures were exposed to 2.5 micrograms concanavalin A/mL to assess their ability to release lymphokines. Cytokine (interleukin (IL)-2, IL-6, interferon-gamma, tumor necrosis factor-alpha) concentration in plasma or cell supernatants was assessed by bioassay. The results indicated that GdCl2 treated mice exhibited a marked reduction in circulating IL-6 levels at both 2 and 24 hours after CLP. Furthermore, the reduction of Kupffer cell number before the onset of sepsis completely prevented the depression of splenocyte IL-2 and interferon-gamma release, capacity. Thus mediators released by Kupffer cells during the systemic inflammatory response to polymicrobial sepsis play a significant role in producing immune dysfunction in resident splenic lymphocytes. In view of this, it appears that modulation of Kupffer cell hyperactivity during sepsis may be a novel approach for maintaining distant organ host defense mechanisms.
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PMID:Mechanism of splenic immunosuppression during sepsis: key role of Kupffer cell mediators. 919 70

Previous studies indicate a profound suppression of tumour necrosis factor alpha (TNF-gamma), IL-1 beta and IL-6 release capacity by peritoneal macrophage (PM phi), splenic macrophage (SM phi) and Kupffer cells (KC) during late sepsis. Such a loss of functional capacity may reduce the animal's ability to ward off infection. Prolactin is known to enhance monocyte, T- and B-lymphocyte immune responses under normal conditions and has beneficial effects on cell-mediated immunity after haemorrhage. In the respect, the dopamine antagonist, metoclopramide, has been reported to increase circulating prolactin levels. Nonetheless, it remains unknown whether prolactin or metoclopramide have any salutary effect on macrophage (M phi) cytokine gene expression following sepsis. To study this, male C3H/HeN mice were subjected to sepsis and immediately thereafter were treated with prolactin (100 micrograms/25 g body weight, s.c.), metoclopramide (100 micrograms/100 g BW, s.c.) or given saline. PM phi, SM phi and KC (only SM phi and KC in metoclopramide-treated animals) were isolated at 24 h after sepsis. The monolayers were stimulated with or without LPS 10 micrograms/ml for 1 h in vitro. Total RNA was extracted and mRNA was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). A significant depression of constitutive and inducible mRNA levels of IL-1 beta, IL-6 and TNF-alpha in all three M phi populations were observed, when compared with shams (with exception of KC IL-6 mRNA in unstimulated cells). Prolactin as well as metoclopramide treatment after the onset of sepsis caused significant elevation of constitutive and inducible cytokine gene expression in all macrophages examined. Thus, prolactin and metoclopramide enhance the depressed M phi gene expression and may be useful in improving cell-mediated immunity during sepsis.
Cytokine 1997 Jun
PMID:Effects of prolactin and metoclopramide on macrophage cytokine gene expression in late sepsis. 919 78

To evaluate the role of tumour necrosis factor (TNF) in gut-derived sepsis, mice were given Pseudomomas aeruginosa strain D4 by bacterial suspension in their drinking water during which time ampicillin (200 mg/kg) was given to disrupt the normal indigenous bacterial flora. Cyclophosphamide was additionally administered to induce bacterial translocation of the P. aeruginosa that had colonized the gastrointestinal tract, and thereby to cause gut-derived sepsis. In this model, TNF-alpha was detected in serum from the next day after the second cyclophosphamide administration, increasing to level of 3 ng/ml in lethal conditions. Average serum TNF-alpha level was significantly higher in mice with bacteraemia than in those without bacteraemia. Treatment with 0.8 microg/kg of recombinant human TNF-alpha (rhTNF-alpha) did not affect the mortality, whereas administration of either 4 and 20 microg/kg of rhTNF-alpha significantly increased the mortality rate in comparison with saline-treated mice. Bacterial counts in liver and blood were significantly higher in 20 microg/kg of rhTNF-alpha treated mice than in saline-treated mice. Treatment with murine anti-TNF-alpha monoclonal antibody significantly reduced the mortality from septic infection. We conclude that TNF-alpha may facilitate bacterial translocation and causes deterioration of gut-derived sepsis due to P. aeruginosa in mice.
Cytokine 1997 Oct
PMID:Adverse effects of tumour necrosis factor in cyclophosphamide-treated mice subjected to gut-derived Pseudomonas aeruginosa sepsis. 934 9

It is apparent from preclinical and clinical research to date that continued evaluation of new and alternative treatment strategies is required to eliminate the obligate periods of neutropenia and thrombocytopenia after acute high-dose irradiation. Future treatment strategies may involve new combinations of cytokines to affect hematopoietic stem cell proliferation and "engineered" cellular grafts to provide short-term in vivo expansion of neutrophils and platelets in an effort to bridge the cytopenic gap until endogenous or transplanted stem cells regenerate the hematopoietic and immune systems. Cytokine-mobilized peripheral blood and cord blood will provide alternative sources of allogeneic stem and progenitor cells in support of primary engraftment, delayed engraftment or secondary failure of the initial graft, as well as starting populations for various ex vivo expansion protocols. Further insights into the relative quality of stem cell populations and the factors that regulate their survival and self renewal, and the identification and roles of adhesion molecules in stem cell mobilization, engraftment, and interaction with the adult marrow microenvironment will provide the basis for future treatment strategies for the radiation-induced hematopoietic syndrome. As our ability to treat the hematopoietic syndrome improves, damage to other organ systems such as the skin, lung, and/or gastrointestinal tissue will emerge as dose-limiting. At the same time, the characterization of receptors for inflammatory cytokines, cytokine receptor antagonists, and anti-endotoxin antibodies has allowed significant insights into the mechanisms and pathogenesis of sepsis. However, translation of this knowledge into a treatment modality for septic patients is precluded by the lack of any clear-cut beneficial effect from the many clinical trials. The research and clinical results presented in this volume and recent conferences reflect the body of knowledge that will lead to further developments in assessment, prophylaxis, and treatment of radiation injuries in the areas of infectious disease and the hematopoietic, gastrointestinal, and cutaneous syndromes.
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PMID:Therapy of radiation injury. 936 12

During gram-negative bacterial sepsis, lipid A, the biologically active moiety of endotoxin (ET), activates monocytes and induces the release of cytokines. PMX-B, a cationic peptide, binds to lipid A and inhibits its activity. Based on this principle, PMX-B was incorporated in polystyrene-derivative fibers, creating a hemoperfusion column (PMX-20R) that removes ET. After in vitro characterization of the cytokine inducing potency of three gram-negative bacterial challenges, the authors evaluated the in vitro efficacy of PMX-20R in a model using 10% human plasma. Cytokine production by peripheral blood mononuclear cells (PBMC) incubated with plasma before and after in vitro hemoperfusion (IVH) was used as the index of ET removal. One hundred forty milliliters of heparinized blood were obtained from healthy volunteers. Forty milliliters were used to harvest PBMC at baseline, and 10% plasma prepared from the rest, was challenged with: 1) 0.01, 1, or 100 ng/ml of purified Escherichia coli ET; or 2) 1:1,000 dilution of E. coli, Pseudomonas aeruginosa, or Klebsiella pneumoniae. IVH was performed at 100 ml/min at 37 degrees C for up to 6 hours. One half milliliter samples, drawn before and at designated time intervals after the start of IVH, were mixed with a 0.5 ml suspension of 5 x 10(6) PBMC/ml from the same donor, and incubated for 24 hours at 37 degrees C. PBMC were subjected to three freeze-thaw cycles, and total tumor necrosis factor alpha (TNFalpha) was measured by radioimmunoassay. Before IVH, TNFalpha production by PBMC incubated with 10% plasma containing 0.01, 1, or 100 ng/ml of purified E. coli ET was 1905+/-391 pg, 2076+/-552 pg, and 5304+/-1001 pg, respectively. After 2 hours of IVH, the respective decrease in TNFalpha production was 82+/-5% (p = 0.005), 78+/-10% (p = 0.01), and 95+/-1% (p = 0.002). Before IVH, TNFalpha production by PBMC incubated with 10% plasma containing 1:1,000 dilution of E. coli, P. aeruginosa or K. pneumoniae was 2896+/-273 pg, 1816+/-122 pg, and 1131+/-125 pg, respectively. After 2 hours of IVH, the respective decrease in TNFalpha production was 83+/-4% (p < 0.001), 53+/-4% (p < 0.001), and 70+/-5% (p < 0.001). When IVH was extended to 6 hours, the further decrease in TNFalpha production was not statistically significant. These results suggest an impressive in vitro removal of ET by PMX-20R from 10% human plasma containing either purified E. coli ET or E. coli, P. aeruginosa, or K. pneumoniae. Further in vitro studies are required, using whole blood challenged with gram-negative bacteria.
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PMID:Endotoxin removal by polymyxin-B immobilized polystyrene-derivative fibers during in vitro hemoperfusion of 10% human plasma. 946 2


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