Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe blunt chest trauma is frequently associated with multiple organ failure and sepsis. Posttraumatic immunosuppression seems to play a major role in their development. However, the immunologic alterations following pulmonary contusion are insufficiently elucidated. Specifically, it remains unknown whether immunocompetent cells located distant from the site of the impact are affected. We therefore aimed to characterize the influence of pulmonary contusion on lymphocytes and splenic macrophages. Male C3H/HeN mice (n = 8-10/group) were anesthetized and subjected to trauma or sham procedure. Blunt chest trauma was induced by a blast wave focused on the thorax. Two or 24 h later, splenocytes and splenic macrophages were isolated and stimulated for 48 h. The cytokine release (IFN-gamma, IL-2, IL-3, IL-10, IL-12, IL-18) from splenocytes as well as from splenic macrophages (TNF-alpha, IL-10, IL-12, IL-18) and plasma levels of TNF-alpha and IL-6 were quantified by ELISA. The results indicate that at 2 h after blunt chest trauma, plasma TNF-alpha and IL-6 were markedly increased. At the same time, no differences in splenocyte cytokine production were detectable. However, at 24 h a significantly depressed cytokine release was observed in trauma animals. Furthermore, splenic macrophages showed a significantly decreased production of TNF-alpha, IL-10, and IL-12 at 24 h and markedly increased release of IL-18 at 2 h after trauma. These results indicate that blunt chest trauma causes severe immunodysfunction of lymphocytes and splenic macrophages. Thus, lung contusion as a localized type of trauma causes dysfunction of immunocompetent cell populations, which are located distant from the site of injury.
 ...
PMID:Blunt chest trauma induces delayed splenic immunosuppression. 1520 2

Lipopolysaccharide (LPS) is an inducer of interleukin (IL)-18, which in turn plays important roles in immune responses. Previously, we reported that tumor necrosis factor (TNF)-alpha production could be detected in human peripheral blood mononuclear cells (PBMCs) treated with relatively low concentration of LPS (1 ng/ml), but that same concentration of LPS could not induce IL-18 production. In the present study, we found that LPS at relatively high concentrations (10-1000 ng/ml) induced IL-18 production in a concentration-dependent manner both in monocytes isolated from PBMC, and that histamine (10(-7) to 10(-4) M) inhibited IL-18 production induced by LPS. The studies using receptor subtype-selective agonists and antagonists suggested that the effect of histamine was mediated by H2 receptor but not by H1, H3 and H4 receptors. Therefore, the stimulation of H2 receptor might be beneficial in the treatment of sepsis through inhibiting LPS-elicited IL-18.
 ...
PMID:Histamine inhibits lipopolysaccharide-induced interleukin (IL)-18 production in human monocytes. 1520 79

Standard renal replacement therapy in acute renal failure (ARF) and end-stage renal disease (ESRD) is based on membrane technology. The transition from natural cellulosic membranes to synthetic membranes has not been associated with improvement in mortality rates. Modifications of dialysis with continuous arteriovenous hemofiltration and hemodiafiltration to remove middle molecular weight toxins, low molecular weight proteins and peptides (LMWP) and cytokines involved in inflammation appear to have reached their limits. High flux dialyzers are not efficient at removing LMWP and for this reason sorbents to augment or replace dialysis have been used in clinical trials. Removal of LMWP such as beta2-microglobulin, leptin, complement factor D, angiogenin, and cytokines such as IL-1, IL-6, IL-10, IL-18 and TNFalpha, have been established in animal models of sepsis, and in ESRD patients using sorbents in conjunction with high flux dialysis. Sorbent devices added to hemodialysis, or alone in inflammatory states, are being studied in diseases which possess a common pathway of systemic inflammatory response syndrome; these states are sepsis, ARF, cardio-pulmonary bypass, in brain dead subjects prior to explantation of donor organs and ESRD.
 ...
PMID:Sorbents in the treatment of renal failure. 1546

The interleukin-1 receptor-associated kinase-1 (IRAK-1) mediates signal transduction from Toll-like/IL-1/IL-18 receptors. Though a critical protective role against Staphylococcus aureus infection has been previously attributed to myeloid differentiation factor 88 (MyD88) and IRAK-4, both also involved in TLR/IL-1/IL-18 signaling, the role of IRAK-1 is unknown. IRAK-1-deficient (IRAK-1-/-) and wild-type mice were inoculated i.v. with 2 x 10(7) or 1 x 10(6) S. aureus per mouse to evaluate the role of IRAK-1 in S. aureus sepsis. Since IRAK-1 transduces IL-1R signals, IL-1R-/- mice were also included in experiments. IRAK-1-/- mice are susceptible to a high dose of S. aureus compared to wild-type controls. In contrast to the high mortality and extensive weight loss seen in IL-1R-deficient mice in response to 1 x 10(6) S. aureus, IRAK-1-/- mice are resistant to this low dose of S. aureus. Thus IRAK-1 plays an important role in the host response to staphylococcal sepsis.
 ...
PMID:IL-1 receptor-associated kinase 1 mediates protection against Staphylococcus aureus infection. 1555 32

Recent data have shown that anti-inflammatory responses to major injury occur immediately after trauma. Interleukin 11 (IL-11), a member of the IL-6 family, is a pleiotropic cytokine with hematopoietic, osteotrophic, and mucosa protective properties, as well as anti-inflammatory functions. IL-11 inhibits synthesis of proinflammatory cytokines, promotes a Th2-type immune response, and improves outcome after shock and sepsis in different animal models. To further investigate the role of IL-11 in the human posttraumatic immune response, we measured plasma levels of IL-11 in 216 multiple-injured patients (mean age of 40 +/- 16 [range 11-81] years; Injury Severity Score [ISS] of 31 +/- 11 [range 16-66] points; 52 women and 164 men) after injury and correlated this with demographics, clinical course, and other laboratory parameters. IL-11 was significantly elevated in polytraumatized patients compared with healthy donors (P <0.0001). The time course of IL-11 in surviving patients was an initial increase after trauma with a decrease during the first 4 weeks, whereas nonsurvivors (n=34) had a significant increase later after injury (4 weeks). IL-11 was significantly higher after abdominal trauma and in men. No correlation between systemic IL-11 and ISS or age was detected. IL-11 correlated significantly with other pro- and anti-inflammatory cytokines such as IL-18. Our data demonstrate elevated levels of systemic IL-11 after multiple injuries; however, the role of a posttraumatic increase of IL-11 has to be further analyzed. In contrast to IL-6, IL-11 in plasma does not correlate with trauma severity and seems to have no clinical relevance to outcome prediction after trauma.
 ...
PMID:Analysis of systemic interleukin-11 after major trauma. 1561 28

Caspase-1-deficient (-/-) mice are protected against sepsis-induced hypotension and mortality. We investigated the role of caspase-1 and its associated cytokines in a nonhypotensive model of endotoxemic acute renal failure (ARF). Mice were injected intraperitoneally with 2.5 mg of LPS that induces endotoxemic ARF. On immunoblot analysis of whole kidney, there was an increase in caspase-1 protein in LPS-treated mice compared with vehicle-treated controls. In LPS-treated mice, the glomerular filtration rate (GFR) was significantly higher in caspase-1 -/- vs. wild-type mice at 16 and 36 h after LPS. To determine the mechanism of this protection, the caspase-1-activated cytokines IL-1beta and IL-18 were investigated. IL-1beta and IL-18 protein were significantly increased in the kidneys of LPS- vs. vehicle-treated mice. To determine the role of these cytokines, mice were treated with recombinant IL-1 receptor antagonist (IL-1Ra) or IL-18-neutralizing antiserum. In LPS-treated mice, GFR was not different in IL-1Ra-treated or IL-18-neutralizing antiserum-treated or combination therapy (IL-1Ra plus IL-18-neutralizing antiserum-treated) compared with control mice. In addition, tubular cell apoptosis, neutrophil infiltration, myeloperoxidase activity, caspase-3 activity, and calpain activity were not different between wild-type and caspase-1 -/- mice with endotoxemic ARF. In LPS- vs. vehicle-treated wild-type mice, renal IL-1alpha was significantly increased. In both LPS- and vehicle-treated caspase-1 -/- mice, renal IL-1alpha was very low. In summary, caspase-1 -/- mice are functionally protected against endotoxemic ARF. Neutralization of IL-1beta and IL-18 is not functionally protective. The role of the intracellular proinflammatory cytokine IL-1alpha in endotoxemic ARF merits further study.
 ...
PMID:Endotoxemic acute renal failure is attenuated in caspase-1-deficient mice. 1564 89

Intrauterine infection induces an intra-amniotic inflammatory response involving the activation of a number of cytokines and chemokines which, in turn, may trigger preterm contractions, cervical ripening and rupture of the membranes. Infection and cytokine-mediated inflammation appear to play a prominent role in preterm birth at early gestations (<30 weeks). The role of infection/inflammation in preterm birth in Europe has been incompletely characterised. The rate of preterm birth in Sweden is lower, and the rate of chorioamnionitis, bacterial vaginosis (BV), neonatal sepsis, and urinary tract infections during pregnancy is lower compared with the USA. In a Swedish population of women with preterm labour or preterm premature rupture of the membranes (PPROM) <34 weeks of gestation, microorganisms were detected in the amniotic fluid in 25% of women with PPROM and in 16% of those in preterm labour. Nearly half of these women had intra-amniotic inflammation defined as elevated interleukin-6 (IL-6) and IL-8, and there was a high degree of correlation between cytokine levels and preterm birth or the presence of microbial colonisation. These data do not support the hypothesis that infection-related preterm birth is less frequent in northern Europe than elsewhere. The intra-amniotic inflammatory response has also been associated with white matter injury and cerebral palsy. We find that in experimental models, induction of a systemic inflammatory response using lipopolysaccharide activates toll-like receptors (TLRs), which produce either white matter lesions or increase brain susceptibility to secondary insults. Recently, IL-18 in umbilical blood was shown to correlate with brain injury in preterm infants and IL-18 deficiency in mice decreases CNS vulnerability.
 ...
PMID:Role of cytokines in preterm labour and brain injury. 1571 88

Abdominal sepsis due to secondary fecal peritonitis following anastomosis insufficiency is a rare but life threatening complication of colorectal surgery. The induction of IFN-gamma by IL-12 is believed to play a key role in sepsis as it promotes antibacterial effector mechanisms such as oxidative burst or nitric oxide induction. The impact of gene deficiency for IL-12 (IL-12p40 KO), oxidative burst (p47(phox) KO), or NO induction (iNOS KO) on the outcome of fecal peritonitis was characterized using the murine Colon Ascendens Stent Peritonitis model (CASP). In the IL-12p40 KO model, 3 and 12 h after surgery, serum cytokine levels of IL-1beta, TNF, IL-18, and IL-10 were analyzed. Expression of IL-1beta, IL-10, IP-10, and MIP-1alpha was measured in lung and liver by RNAse Protection Assay. IL-12p40 and iNOS-deficient mice exhibited a significantly higher susceptibility to CASP as compared to the controls, whereas no significant difference was observed in p47(phox) KO mice. Absence of IL-12 resulted in delayed expression of proinflammatory cytokines and chemokines in both the liver and the lung, and was associated with significant reduction of IL-1beta levels in the serum 12 h after CASP. IL-12 and iNOS possess protective functions in fecal murine peritonitis. Surprisingly, no significant contribution of oxidative burst to the immune response was observed. Overall, these findings suggest that IL-12 deficiency causes a profound delay of the immune response after polymicrobial challenge resulting in significantly increased susceptibility in the CASP model.
 ...
PMID:Impact of interleukin-12, oxidative burst, and iNOS on the survival of murine fecal peritonitis. 1575 96

We examined the effects of beta2-adrenergic receptor (beta2-AR) agonists on monocyte-derived cytokines, interleukin (IL)-18 and IL-12 production in lipopolysaccharide (LPS)-stimulated monocytes derived from human peripheral blood mononuclear cells (PBMCs), as in vitro model of sepsis. The study found that beta2-AR agonists inhibited IL-18 and IL-12 production in monocytes, and that AR agonist activity was antagonized by the selective beta2-AR antagonist, butoxamine. The selective beta2-AR agonists salbutamol and terbutaline induced a similar inhibitory pattern of IL-18 and IL-12 production. IL-12 production induced by LPS was inhibited by anti-IL-18 Ab, but IL-18 production by LPS was not inhibited by anti-IL-12 Ab, showing that LPS induced IL-18 production without IL-12 production. Therefore, the stimulation of beta2-AR might be beneficial in the treatment of sepsis through inhibiting LPS-elicited IL-18.
 ...
PMID:Beta2-adrenergic receptor stimulation inhibits LPS-induced IL-18 and IL-12 production in monocytes. 1599 44

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.
 ...
PMID:[Indicators for early prediction of outcome in sepsis]. 1609 22


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>