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)

Anti-inflammatory substances are released during septic shock that modulate monocyte function. Decreased monocyte responsiveness to bacterial toxins and decreased expression of human-leukocyte-associated antigen-DR (HLA-DR) have been reported during septic shock and critical illness. Impaired antigen presentation has been inferred from these observations but has not been demonstrated. We assessed antigen presentation and costimulatory molecule expression in 12 age-matched control subjects, 10 noninfected critically ill patients (CINS), and 17 critically ill patients with sepsis (CIS). Antigen presentation was assessed by using in vitro lymphocyte 5-bromo-2-deoxyuridine (BrdU) incorporation in response to tetanus toxoid. The expression of HLA-DR and the costimulatory molecules CD28, CD86, and CTLA-4 was assessed by flow cytometry. Serum interleukin-10 (IL-10) was also measured by enzyme-linked immunosorbent assay. Serum IL-10 levels were significantly elevated in CIS patients (91 +/- 38 pg/mL) as compared with levels in control subjects (5 +/- 4 pg/mL)(P < .05). Lymphocyte BrdU incorporation increased by 710% +/- 243% in control subjects but by only 144% +/- 62% in CIS patients and 76% +/- 31% in CINS patients (P < .01 vs control). Monocyte HLA-DR expression, monocyte CD86 expression, and lymphocyte CD28 expression were significantly decreased in CIS patients (P < .01) as compared with control subjects. Conversely, lymphocyte CTLA-4 expression was significantly increased in CIS patients (P < .05 vs control). Monocyte CD86 expression was also significantly decreased in CINS patients as compared with control subjects. These data indicate that antigen presentation is decreased in critically ill patients with sepsis. This appears in part related to decreased expression of HLA-DR and the costimulatory molecules CD86 and CD28. Increased expression of the negative signal receptor CTLA-4 may also impair antigen presentation in patients with sepsis.
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PMID:Decreased response to recall antigens is associated with depressed costimulatory receptor expression in septic critically ill patients. 1069 60

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

The dendritic cell (DC) is the most potent APC of the immune system, capable of stimulating naive T cells to proliferate and differentiate into effector T cells. Recombinant adenovirus (Adv) readily transduces DCs in vitro allowing directed delivery of transgenes that modify DC function and immune responses. In this study we demonstrate that footpad injection of a recombinant Adv readily targets transduction of myeloid and lymphoid DCs in the draining popliteal lymph node, but not in other lymphoid organs. Popliteal DCs transduced with an empty recombinant Adv undergo maturation, as determined by high MHC class II and CD86 expression. However, transduction with vectors expressing human IL-10 limit DC maturation and associated T cell activation in the draining lymph node. The extent of IL-10 expression is dose dependent; transduction with low particle numbers (10(5)) yields only local expression, while transduction with higher particle numbers (10(7) and 10(10)) leads additionally to IL-10 appearance in the circulation. Furthermore, local DC expression of human IL-10 following in vivo transduction with low particle numbers (10(5)) significantly improves survival following cecal ligation and puncture, suggesting that compartmental modulation of DC function profoundly alters the sepsis-induced immune response.
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PMID:Increased survival in sepsis by in vivo adenovirus-induced expression of IL-10 in dendritic cells. 1190 99

The phenotype and function of peripheral blood monocytes change after trauma and during sepsis. The aim of the study was to evaluate monocyte expression of human leucocyte antigen (HLA)-DR and Fc receptor III (FcR III) (CD16) in neonates and small children with high risk of sepsis (hospitalized at the intensive care unit). The reduced proportion of CD14+HLA-DR+ monocytes was observed in all patients at the intensive care unit, while the increase of CD16 expression on monocytes was observed in the course of sepsis. The measurement of CD16 expression on monocytes also proved to be more useful for monitoring patient. The proportion of both CD14dimCD16+ and CD14highCD16+ monocytes increased during sepsis; however, monocytes showed reduced ability to phagocytose Escherichia coli, compromised ability to cooperate with T cells and reduced CD86 expression in parallel to HLA-DR depression. The reduced interleukin (IL)-1 but rather increased IL-10 production was associated with sepsis. The differences between CD14+CD16+ monocytes of healthy donors and patients with sepsis are discussed.
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PMID:CD14+CD16+ monocytes in the course of sepsis in neonates and small children: monitoring and functional studies. 1202 67

Neisseria meningitidis and Neisseria gonorrhoeae are Gram-negative pathogenic bacteria responsible for bacterial meningitis and septicemia, and the sexually transmitted disease gonorrhea, respectively. Porins are the most represented outer membrane proteins in the pathogenic Neisseria species, functioning as pores for the exchange of ions, and are characterized by a trimeric beta-barrel structure. Neisserial porins have been shown to act as adjuvants in the immune response via activation of B cells and other antigen-presenting cells (APCs). Their effect on the immune response is mediated by upregulation of the costimulatory molecule B7-2 (CD86) on the surface of APCs, an effect that is Toll-like receptor 2- and MyD88-dependent. The effect of neisserial porins on the immune system also involves interaction with components of the complement cascade. Furthermore, neisserial porins co-localize with mitochondria of target cells, where they appear to modulate apoptosis.
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PMID:The role of porins in neisserial pathogenesis and immunity. 1259 31

Neisseria meningitidis serogroup B is a major cause of life-threatening meningitis and septicemia worldwide, and no effective vaccine is available. Initiation of innate and acquired immune responses to N. meningitidis is likely to be dependent on cellular responses of dendritic cells (DC) to antigens present in the outer membrane (OM) of the meningococcus. In this study, the responses of human monocyte-derived DC (mo-DC) to OM isolated from parent (lipopolysaccharide [LPS]-replete) meningococci and from a mutant deficient in LPS were investigated. Parent OM selectively up-regulated Toll-like receptor 4 (TLR4) mRNA expression and induced mo-DC maturation, as reflected by increased production of chemokines, proinflammatory cytokines, and CD83, CD80, CD86, CD40, and major histocompatibility complex (MHC) class II molecules. In contrast, LPS-deficient OM selectively up-regulated TLR2 mRNA expression and induced moderate increases in both cytokine production and expression of CD86 and MHC class II molecules. Preexposure to OM, with or without LPS, augmented the allostimulatory properties of mo-DC, which induced proliferation of naive CD4+ CD45RA+ T cells. In addition, LPS-replete OM induced a greater gamma interferon/interleukin-13 ratio in naive T cells, whereas LPS-deficient OM induced the reverse profile. These data demonstrate that components of the OM, other than LPS, are also likely to be involved in determining the levels of DC activation and the nature of the T-helper immune response.
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PMID:Activation of human dendritic cells is modulated by components of the outer membranes of Neisseria meningitidis. 1450 Apr 78

Dendritic cells (DCs) are professional antigen-presenting cells that act as sentinels in the cell-mediated response against invading pathogens associated with septic challenge. The purpose of the present study was to determine whether there is a loss of dendritic cells and/or changes in function of these cells in septic mice. Here we report that the number of DCs, in both spleen and peritoneum, decreased over 24 h postsepsis [cecal ligation and puncture (CLP)] when compared with sham. The most dramatic change was seen in the peritoneal cavity. This decrease appeared to be caused mainly by the depletion of immature DCs rather than mature DCs. This change was LPS independent and minimally affected by FasL; however, overexpression of human Bcl-2 gene provides protection of the septic peritoneal DCs. Moreover, although the level of IL-12 release decreased significantly in splenic DCs obtained from CLP mice, IL-12 secretion was markedly elevated by peritoneal DCs as well as in both plasma and peritoneal fluid at 24 h post-CLP. In peritoneal cells, the expression of CD40, CD80, and CD86 was unchanged, but their respective ligands CD40L, CD28, and CD152 all increased in mice 24 h after CLP, although no such change was observed in splenocytes. Regardless of the presence or absence of antigen, peritoneal DCs from CLP mice showed higher capacity to stimulate T-cell proliferation than those cells from the sham control. However, splenic DCs from CLP mice only showed augmented capacity to induce antigen-dependent stimulation of T-cell proliferation. Together, these data indicate that sepsis produces divergent functional changes in splenic and peritoneal DC populations.
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PMID:Polymicrobial sepsis induces divergent effects on splenic and peritoneal dendritic cell function in mice. 1525 86

Dendritic cells (DCs) play a key role in critical illness and are depleted in spleens from septic patients and mice. To date, few studies have characterized the systemic effect of sepsis on DC populations in lymphoid tissues. We analyzed the phenotype of DCs and Th cells present in the local (mesenteric) and distant (inguinal and popliteal) lymph nodes of mice with induced polymicrobial sepsis (cecal ligation and puncture). Flow cytometry and immunohistochemical staining demonstrated that there was a significant local (mesenteric nodes) and partial systemic (inguinal, but not popliteal nodes) loss of DCs from lymph nodes in septic mice, and that this process was associated with increased apoptosis. This sepsis-induced loss of DCs occurred after CD3(+)CD4(+) T cell activation and loss in the lymph nodes, and the loss of DCs was not preceded by any sustained increase in their maturation status. In addition, there was no preferential loss of either mature/activated (MHCII(high)/CD86(high)) or immature (MHCII(low)/CD86(low)) DCs during sepsis. However, there was a preferential loss of CD8(+) DCs in the local and distant lymph nodes. The loss of DCs in lymphoid tissue, particularly CD8(+) lymphoid-derived DCs, may contribute to the alterations in acquired immune status that frequently accompany sepsis.
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PMID:Characterization of the systemic loss of dendritic cells in murine lymph nodes during polymicrobial sepsis. 1532 63

Control of dendritic cell (DC) function is critical for strategies to modulate innate and acquired immune responses. We examined whether transduction of murine DCs with adenoviral vectors (Adv) expressing interleukin (IL)-10 could alter their phenotype and T cell stimulatory function. Murine bone marrow-derived DCs were transduced with AdV encoding human IL-10 or green fluorescent protein (GFP). Whereas transduction of immature DCs with AdV/GFP resulted in dose-dependent maturation, DCs transduced with Adv/IL-10 maintained an immature state with low major histocompatibility complex (MHC) class II, CD86, and IL-12 expression. The Adv/IL-10 transduced DCs were phenotypically unique, characterized by suppression of IL-12 expression, failure to stimulate Th1 or Th2 cytokine responses, and retained capacity to endocytose antigen. Importantly, Adv/IL-10-transduced DCs were biologically active in vivo, in that administration of these DCs into mice before a generalized peritonitis significantly improved survival. We conclude that Adv/IL-10 transduction of DCs provides an efficient means to modulate DC function. The capacity to modify DCs by adenoviral expression of IL-10 may provide a novel ex vivo or in vivo approach to mitigate acute and chronic inflammatory diseases like sepsis.
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PMID:Functional modification of dendritic cells with recombinant adenovirus encoding interleukin 10 for the treatment of sepsis. 1589 2

Normal turnover of body tissues yields apoptotic cells while infections cause tissue injuries and cell necrosis. The interaction of these dying cells with dendritic cells (DCs) may provide immunological instructions leading to either immune tolerance or activation. We hypothesize that neonatal and adult DCs differ in their responses to dying cells, thereby contributing to the observed differences in immune responses between neonates and adults. We compare the outcome of interaction of cord and adult blood-derived DCs with dying Epstein-Barr-virus-transformed lymphoblastoid cells (LCLs) and the responsiveness to lipopolysaccharide. While cord DCs were able to phagocytose both apoptotic and necrotic LCLs, the subsequent responses differed significantly from those of adult DCs. Interaction of adult DCs with necrotic but not early apoptotic LCLs resulted in high expression of DC costimulatory molecules (CD80/CD86) and activation markers (CD83), production of both proinflammatory and anti-inflammatory cytokines (tumour necrosis factor-alpha, interleukin-10), and strong T-cell-stimulating activities. In contrast, in response to either necrotic or apoptotic LCLs, cord DCs had minimal up-regulation of those DC functional markers, little cytokine production and poor stimulation on T-cell proliferation. In response to lipopolysaccharide, however, both adult and cord DCs produced comparable levels of tumour necrosis factor-alpha and interleukin-10, but only adult DCs produced interleukin-12(p70). Taken together, these results suggest that neonatal DCs generally favour immune tolerance with minimal activation and cytokine production, except in extremely dangerous situations, such as bacterial sepsis, when neonatal DCs may produce certain types of cytokines and stimulate T-cell proliferation.
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PMID:Differential responses of cord and adult blood-derived dendritic cells to dying cells. 1610 13


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