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)

The aim of this study was to identify a novel immunological indicator useful for the early diagnosis (through a rapid and single determination) of neonatal sepsis (NS). Peripheral blood samples were taken from 63 neonates, who were classified into four groups: proven NS (n = 17); clinical NS (n = 14); disease without infection (n = 17); and healthy newborns (n = 15). Neutrophil expression of CD64, CD43, CD44, CD50, CD62L and Mac-1, and plasma levels of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha) and soluble L-selectin (sCD62L), were determined. Expression of CD64 was significantly enhanced in the group with proven sepsis and clinical NS compared to newborns without infection (p < 0.05). Eight newborns with proven or clinical sepsis, but only one with disease without infection, showed an increased percentage of CD64+ cells (diagnostic specificity = 96.8%). No significant differences were found in the expression of the other leucocyte differentiation antigens studied. As previously described, TNF-alpha and IL-6 levels were significantly elevated in newborns with proven or clinical sepsis compared to neonates without infection (p < 0.05). Our results suggest that, through a single determination, the enhanced expression of CD64 is a highly specific indicator of NS, although its diagnostic sensitivity is low (25.8%). In contrast, we found that plasma levels of IL-1beta and sCD62L, as well as the expression of Mac-1, CD43, CD44, CD50, and CD62L, do not appear to be useful for the diagnosis of NS.
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PMID:Expression of CD64 as a potential marker of neonatal sepsis. 1243 Nov 90

Paradoxically, the host response to severe sepsis may lead to immunosuppression, thereby favoring nosocomial infections. We examined the role of the two IL-12 isoforms, bioactive IL-12p70 and regulatory IL-12p40, in 16 patients with severe sepsis. We compared the capacity of purified blood and alveolar phagocytes [polymorphonuclear neutrophils (PMN) and monocytes/macrophages] to secrete each isoform. Blood monocytes had normal basal secretions. In contrast, a marked imbalance was observed after ex vivo stimulation by lipopolysaccharide plus IFN-gamma, with significantly lower IL-12p70 production and higher IL-12p40 production. Conversely, stimulated IL-12p40 production by the patients' blood PMN tended to be impaired, as was their cell-surface beta2 integrin and L-selectin expression, known as markers of cell activation. In the patient's bronchoalveolar lavage fluid, the production of both IL-12 isoforms after ex vivo stimulation was significantly lower with alveolar macrophages than with autologous blood monocytes and significantly higher with alveolar PMN than with autologous blood PMN. This sheds new light on the potential role of PMN in local modulation of inflammation, via secretion of the anti-inflammatory IL-12 p40 subunit. The imbalance between the bioactive and regulatory IL-12 isoforms, which is probably designed to control excessive inflammation, may also make septic patients more susceptible to nosocomial infection.
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PMID:Regulation of interleukin 12 p40 and p70 production by blood and alveolar phagocytes during severe sepsis. 1367 43

L-Selectin is an adhesion molecule shed from the surface of lymphocytes and granulocytes upon activation. Soluble L-selectin in the plasma can thus reflect immune activation and is elevated in several pathological states. Our objective was to evaluate plasma levels of L-selectin as an immune activation marker in neonates and to determine whether it can serve as a marker of infection, either neonatal or congenital, or if it is affected by the mode of delivery and obstetrical or perinatal complications. A solid-phase ELISA was used on 89 sera from neonates less than 2 days of age, according to the manufacturer's instructions. Levels of soluble L-selectin in the neonate were lower than those of older infants and children and comparable to the levels seen in adults. There was no difference between levels of soluble L-selectin of premature (median, 1172 ng/ml) and full-term babies (median, 1151 ng/ml) or between babies born via vaginal (median, 1233 ng/ml) or cesarean delivery (median, 1146 ng/ml). Conditions such as preeclampsia or administration of steroids to the mother did not affect the levels of L-selectin in the neonate. In contrast, the presence of maternal clinical chorioamnionitis resulted in an increase in levels of L-selectin in the neonate (median, 1377 vs 1072 ng/ml, p = 0.02), as did neonatal sepsis (median, 1331 vs 1149 ng/ml, p = 0.026). Soluble L-selectin, and thus immune activation level, is highest in neonates with neonatal infection and needs to be further evaluated as a surrogate marker for diagnosing sepsis in the neonate.
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PMID:Soluble L-selectin, a marker of immune activation, in neonatal infection. 1459 21

An important virulence factor of the pathogenic fungus Cryptococcus neoformans is its polysaccharide capsule. The capsular polysaccharides glucuronoxylomannan (GXM), galactoxylomannan (GalXM) and the mannoproteins (MPs) display various immunomodulatory effects on the host response, such as the inhibition of phagocytosis, suppression of T-cell mediated immunity, and induction of immunogenic tolerance. Moreover, these capsular polysaccharides are able to interfere with the migration of phagocytes despite adequate stimulation of chemokine production and their concerted action accounts for the mild inflammatory response often observed in cryptococcosis. Different mechanisms contribute to this phenomenon. First, cryptococcal polysaccharides impair leukocyte migration towards chemoattractants. A combination of the intrinsic chemoattracting properties of circulating polysaccharides and the ability to induce cross-desensitization of chemokine receptors prevents leukocytes from leaving the bloodstream and migrating towards inflammatory site. Polysaccharide-induced repressive effects on the C5a receptor expression on neutrophils may also add to this impaired chemokinesis. Second, polysaccharides interfere with leukocyte adhesion to and migration through the endothelium. Both GXM and MP-4 induce L-selectin shedding from the surface of leukocytes; hence, interference with leukocyte rolling on the endothelium can be expected. GXM also interferes with the subsequent process of firm leukocyte adhesion to the endothelium in vitro. Thirdly, capsular polysaccharides enhance the production of anti-inflammatory interleukin-10 (IL-10) and induce tumor necrosis factor-alpha (TNFalpha) receptor loss from the surface of neutrophils. The capacity to reduce neutrophil influx makes cryptococcal polysaccharides interesting compounds to study in clinical models of inflammation (i.e.; sepsis, auto-immune disorders) in which leukocyte influx can be potentially damaging to host tissues.
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PMID:Effects of the capsular polysaccharides of Cryptococcus neoformans on phagocyte migration and inflammatory mediators. 1475 21

Both route and severity of infection may influence immunomodulator agents in sepsis. We studied the effect of each variable on HRL-3, an L-selectin-directed MAb that inhibits neutrophil function, in a rat sepsis model. Animals (n = 800) were randomized to be treated with either HRL-3 or placebo and to receive Escherichia coli either intravenously (IV) or intrabronchially (IB) in doses producing low or high mortality rates. Animals received antibiotics and were observed for 168 h. Route but not dose of E. coli altered the effects HRL-3 on mortality rate (mean hazards ratio +/- SE). With IV E. coli, compared with control, HRL-3 was beneficial and reduced the hazards ratio both early (0 to 6 h; -0.75 +/- 0.23) and late (6 to 168 h; -0.72 +/- 0.36) (P = 0.001 and 0.04, respectively, over all E. coli doses). In contrast, with IB E. coli HRL-3 reduced the hazards ratio early (-1.1 +/- 0.36) but worsened it late (0.87 +/- 0.23) (P = 0.002 for both effects over all E. coli doses) in patterns significantly different from IV E. coli (P < 0.0001). Compared with control, although HRL-3 did not alter lung neutrophil numbers or injury score at 6 or 168 h with IV E. coli (P = ns for all), it reduced both early and increased them late with IB E. coli (P </= 0.05 for all comparing 6 with 168 h). Thus immunomodulators inhibiting neutrophil function, although potentially beneficial with sepsis due to intravascular infection, may be harmful with extravascular infection regardless of severity.
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PMID:Neutrophil inhibition with L-selectin-directed MAb improves or worsens survival dependent on the route but not severity of infection in a rat sepsis model. 1567 32

Sepsis is still a major cause of postoperative morbidity and mortality. Numerous biochemical indicators have been evaluated regarding their potential in predicting prognosis in sepsis. Generally, one must differentiate between indicators: those for preoperative detection of patients at risk for lethal sepsis and those for early prediction of lethal outcome of septic complications. The first include the analysis of mononuclear phagocyte interleukin (IL)-12-synthesizing capability. Reduced IL-12 levels were associated with higher lethality. Cytokine-associated gene polymorphisms such as the loss of monocyte HLA-DR expression and homozygotism for the tumor necrosis factor B2 allele have a place in preoperative risk evaluation, as they were associated with worse prognosis in sepsis. Among the most important biochemical indicators for early prediction of lethal outcome in sepsis are decreased L-selectin and elevated IL-18, IL-6, and PCT plasma concentrations. Increased nuclear factor kappaB activity in mononuclear phagocytes and elevated calcitonin gene-related protein plasma concentrations were associated with unfavourable prognosis.
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PMID:[Indicators for early prediction of outcome in sepsis]. 1609 22

Adhesion molecules may play a role in the evolution and severity of neonatal sepsis. The purposes of this study were to determine whether serum soluble intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, L-selectin, and P-selectin levels are useful tools in the diagnosis of proven sepsis in newborn infants, and whether their levels are related to the clinical severity of the disease. A cohort of 25 consecutive newborns meeting criteria for clinical sepsis, 10 hemoculture-negative (HC - ) and 15 hemoculture-positive (HC + ), were prospectively followed and compared with 12 healthy newborns (six </= 38 weeks of gestational age and six >/= 39 weeks). Serum soluble (s)ICAM-1, sVCAM-1, sL-selectin, and sP-selectin concentrations were measured at the time of the septic workup, then followed by up to three determinations in each newborn every third day. The Score for Neonatal Acute Physiology (SNAP)-II severity was assessed at the moment of highest clinical severity of the disease. At the beginning of sepsis, sICAM-1 levels increased in both groups, being higher in HC + sepsis than in HC - ; sVCAM-1 only increased slightly in HC + sepsis. Soluble ICAM-1 levels were independently related to group of sepsis, and not to days of life. The best initial sICAM-1 cutoff level for diagnosing HC + neonatal sepsis was 274 microg/L. The highest sICAM-1 levels were positively correlated with SNAP-II scores. Soluble L-selectin and sP-selectin did not change. Soluble ICAM-1 levels increased in HC - and HC + sepsis, but concentrations > 274 microg/L suggest HC + sepsis. These levels were related to the clinical severity of the disease. Soluble VCAM-1 levels increased only slightly in HC + sepsis. Soluble L-selectin and sP-selectin did not change.
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PMID:Serum soluble ICAM-1, VCAM-1, L-selectin, and P-selectin levels as markers of infection and their relation to clinical severity in neonatal sepsis. 1756 56

Selenium therapy in patients with severe sepsis improves clinical outcome and has been associated with increased activity of the selenoprotein glutathione peroxidase. However, the mechanism of the observed beneficial effects remains unclear. We determined the effect of selenium treatment on the monocyte adhesion molecule L-selectin and L-selectin-related monocyte functions in vitro and transferred our findings to an in vivo mouse model. Monocytes were purified, cultured, and incubated in the presence or absence of supplemented selenium and metalloproteinase (MP) inhibitors for up to 16 h. Expression of L-selectin was unaffected after 2 and 6 h but decreased after 16 h of incubation in the presence of selenium. Soluble L-selectin (sL-selectin) in the supernatant was determined by ELISA. A 2.3-fold increase as a result of shedding of L-selectin was observed after 16 h of selenium treatment. Addition of the MP inhibitors GM6001, TNF-alpha-converting enzyme inhibitor 2, or GW280264X strongly reduced selenium-induced L-selectin shedding, indicating a MP-dependent mechanism. The functional consequences of L-selectin shedding were examined in a flow chamber model. Selenium-treated monocytes showed significantly decreased rolling and adhesion to the L-selectin ligand Sialyl-Lewis(a) under conditions of venous shear stress (0.5 dyne/cm(2)). Selenium treatment of C57BL6 mice led to increased serum levels of sL-selectin, underscoring the in vivo relevance of our findings. We describe a selenium-induced down-regulation of L-selectin on monocytes as a consequence of MP-dependent shedding of this membrane-anchored adhesion molecule. The impairment of monocyte adhesion by selenium supplementation may represent an important, underlying mechanism for the modulation of inflammatory reactions in patients with severe sepsis.
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PMID:Selenium supplementation induces metalloproteinase-dependent L-selectin shedding from monocytes. 1830 78

LPSs getting access to the circulation of mammalian organisms cause typical systemic inflammatory reactions with symptoms characteristic for acute sepsis. One possibility to attenuate LPS effects is to expose a host to a challenge with low LPS doses, which results in the establishment of "endotoxin tolerance" (ET). Because the microcirculation is of particular importance in LPS action, it seemed of interest to analyze leukocyte-endothelial interactions in the mesentery and liver once endotoxin tolerance has been established and are challenged with LPS. The mesenteric and hepatic microcirculation was investigated by intravital microscopy. After induction of ET LPS, shock was induced by i.v. injection of LPS, and microcirculation of the mesentery and liver was examined. Endotoxin tolerance resulted in reduced ex vivo TNF-alpha synthesis of whole blood. In vivo LPS caused no increase of body temperature. In sinusoids, LPS challenge increased adherence of leukocytes in naive rats, which was almost completely prevented by ET induction. In contrast, in postsinusoidal venules, leukocyte adherence was more intense after ET induction and subsequent to LPS application. Similarly, in postcapillary mesenteric venules, increased adherence of leukocytes after LPS challenge in the ET group was observed. After LPS injection, the endothelial barrier was more disturbed in the nontolerant group when compared with the ET group. Soluble L-selectin and intercellular adhesion molecule were elevated in both ET and untreated rats. Endotoxin tolerance influences leukocyte-endothelial interaction differentially depending on organ and vessel area.
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PMID:Microcirculatory alterations of hepatic and mesenteric microcirculation in endotoxin tolerance. 1838 90

The essential trace element selenium (Se), in the form of selenoproteins, plays a pivotal role in the antioxidant defense system of the cell. There is evidence that Se may confer benefits in patients with inflammatory disease and even infectious diseases like HIV. Furthermore, in patients with severe sepsis, characterized by an increase in reactive oxygen species and low endogenous anti-oxidative capacity, as well as in patients with systemic inflammatory response syndrome, Se supplementation may reduce mortality and improve the clinical outcome, respectively. The nuclear factor kappa-B (NF-kappaB) signaling pathway has been associated with enhanced inflammatory response and its activation has been significantly correlated with interleukin-6 and TNF-alpha production. Selenium may inhibit the activation of NF-kappaB by modulating selenoprotein genes expression. Moreover, Se supplementation in chronic inflammation restores the depleted hepatic and serum Se levels by increasing selenoprotein biosynthesis leading to suppressed CRP production thereby attenuating the inflammatory process. Se increases shedding of L-selectin from monocytes while decreasing soluble L-selectin, which has been reported to be associated with high mortality in patients with sepsis. These mechanisms are likely to contribute to the modulatory effects of an increased Se status on the inflammatory response. This review evaluates some apparently key mechanisms of the anti-inflammatory action of selenium and advocates Se supplementation as a modulator of inflammatory response in infectious and autoimmune disease. Prospective, randomized, controlled studies must be performed to provide a greater degree of certainty.
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PMID:Selenium and inflammation: underlying anti-inflammatory mechanisms. 1941 16


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