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)

Group B streptococcal antigens stimulated tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), and IL-6 production in human blood cultures in a concentration- and time-dependent fashion. The minimal concentrations of type-specific polysaccharides, lipoteichoic acid, and group-specific polysaccharide required to produce these effects were, respectively, 0.01, 1, and 10 microg/ml. Cell separation experiments indicated that monocytes were the cell type mainly responsible for cytokine production. Time course studies indicated that TNF-alpha was released before the other cytokines. TNF-alpha, however, did not appear to directly induce IL-1beta, as shown by blockade experiments with anti-TNF-alpha antibodies. IL-6 levels were moderately but significantly decreased by anti-TNF-alpha. These data indicate that several products from group B streptococci are able to directly stimulate human monocytes to release TNF-alpha, IL-1beta, and IL-6. These findings may be clinically relevant, since proinflammatory cytokines can mediate pathophysiologic changes during sepsis.
 ...
PMID:Soluble antigens from group B streptococci induce cytokine production in human blood cultures. 931 1

Glucocorticoids are potent anti-inflammatory and immunosuppressive therapeutic agents. The protective effect of dexamethasone (DEX) on hepatic phosphoenolpyruvate carboxykinase (PEPCK) transcript level, hepatic NF-kB (nuclear factor-kB) activation, and serum tumor necrosis factor alpha (TNF) formation was investigated in peritoneal sepsis induced by cecal incision in rats. For the control the rats were sham-operated with laparotomies only. Each group (N = 6) was pretreated with either normal saline (NS) or DEX before surgery (NS/Sham, NS/Sepsis, DEX/Sham, and DEX/Sepsis). At 3 hr post cecal incision, DEX treatment inhibited sepsis-induced hepatic NF-kB activation by 23%, suppressed circulating TNF by 50%, reduced serum glucose by 36%, reduced hepatic glycogen depletion by 76%, and attenuated PEPCK mRNA level. These findings suggested that DEX treatment was beneficial in attenuating glucose dyshomeostasis and significantly inhibited two sepsis-induced inflammatory mediators, NF-kB and TNF, in the early phase of peritoneal sepsis. However, in the late (6 hr) septic phase, DEX treatment inhibited serum TNF by 69%, but had no effect on NF-kB activation, glycogen depletion, and PEPCK mRNA level suggesting liver function failure injury.
 ...
PMID:Effect of dexamethasone on NF-kB activation, tumor necrosis factor formation, and glucose dyshomeostasis in septic rats. 935 35

In contrast to the anticipation that in sepsis granulocyte colony-stimulating factor (G-CSF) would overactivate the nonspecific immune system by recruiting and priming leukocytes with consequent aggravation of inflammatory tissue lesions, recombinant (r) G-CSF pretreatment was protective in various experimental non-neutropenic models of inflammation. The mechanisms of protection, however, are not fully understood. Using intravital fluorescence microscopy, we show that rG-CSF enhances leukocyte endothelial cell interaction within the microvasculature of normal rat livers, whereas rG-CSF pretreatment of animals exposed to lipopolysaccharide (LPS) attenuates the LPS-induced leukocytic response, including stasis in sinusoids as well as rolling and adherence in postsinusoidal venules with subsequent tissue infiltration. Moreover, rG-CSF, which did not affect Kupffer cell activity in normal rat livers, reduced the immediate activation of Kupffer cells on LPS exposure, as indicated in vivo by the delayed adherence/phagocytosis of intra-arterially administered latex particles associated with attenuation of proinflammatory cytokine release (tumor necrosis factor alpha and interleukin-6). Finally, rG-CSF reduced LPS-induced nutritive perfusion failure and hepatocellular excretory dysfunction. This study provides evidence for a distinct, possibly tumor necrosis factor alpha-dependent modulation of LPS-induced cellular response within the liver by rG-CSF, thereby achieving protection against microcirculatory perfusion failure and hepatic dysfunction.
 ...
PMID:Immunomodulatory action of G-CSF in a rat model of endotoxin-induced liver injury: an intravital microscopic analysis of Kupffer cell and leukocyte response. 940 Aug 11

Clinicians are constantly challenged by patients who demonstrate the ill effects of an uncontrolled host inflammatory response. Patients with sepsis and adult respiratory distress syndrome (ARDS) are frequently encountered examples of this syndrome. Despite advances in intensive care, mortality from these syndromes remains unchanged over the past two decades. In order to gain a better understanding of this pathophysiological response and to identify more specific therapeutic targets, the techniques of molecular biology have been applied to in vivo inflammatory models. Recent data indicate that the inflammatory response is dependent on the presence of both cytokines and adhesion molecules that mediate neutrophil-endothelial cell adhesive interactions. In this article, we review our experience using a lung model of inflammation that has provided insight into the events leading to injury. Cytokines [particularly, interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha)], and endothelial, as well as leukocyte, adhesion molecules appear to coordinate a cascade of interactions between leukocytes and endothelial cells, which results in tissue injury.
 ...
PMID:The role of cytokines and adhesion molecules in the development of inflammatory injury. 941 37

To systematically elucidate the gene expression of inflammatory and immune modulators following middle cerebral artery occlusion (MCAO) in the rat, we studied interleukin-10 (IL-10) along with tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and interleukin-2 (IL-2). Gene expression of these cytokines was studied ipsilateral and contralateral to the MCAO, with mRNA expression levels evaluated 2, 4, 6, 8 and 12 h following permanent MCAO by reverse transcriptase polymerase chain reaction (RT-PCR). In the ischemic hemisphere TNF-alpha and IL-1beta mRNA increased at 2 h following MCAO and peaked at 6 h, with IL-10 mRNA detected only at 6 h. Contralaterally, both TNF-alpha and IL-1beta mRNAs were expressed with a similar pattern to that in the ischemic hemisphere, but at lower levels, with no contralateral IL-10 expression. There was no difference in IL-2 gene expression between control and experimental animals in either hemisphere. These results demonstrate that IL-10 and TNF-alpha, IL-1beta gene expression is induced early following MCAO. The temporal profile of these cytokines is similar to that seen in sepsis, where TNF-alpha induces IL-10; subsequently IL-10 inhibits TNF-alpha expression. The similarity of the temporal profile of cytokine expression in sepsis and cerebral ischemia suggests that IL-10 should be studied as a potential inhibitor of TNF-alpha production in ischemic brain tissue. The factors inducing contralateral expression of the inflammatory cytokines, TNF-alpha and IL-1beta, along with the potential clinical significance of this remote cytokine gene expression, merit further study.
 ...
PMID:Gene expression of IL-10 in relationship to TNF-alpha, IL-1beta and IL-2 in the rat brain following middle cerebral artery occlusion. 941 30

Immune neuroendocrine interactions are vital for the individual's survival in certain physiopathological conditions, such as sepsis and tissular injury. It is known that several animal venoms, such as those from different snakes, are potent neurotoxic compounds and that their main component is a specific phospholipase A type 2 (PLA2). It has been described recently that the venom from Crotalus durissus terrificus [snake venom (SV), in the present study] possesses some cytotoxic effect in different in vitro and in vivo animal models. In the present study, we investigated whether SV and its main component, PLA2 (obtained from the same source), are able to stimulate both immune and neuroendocrine functions in mice, thus characterizing this type of neurotoxic shock. For this purpose, several in vivo and in vitro designs were used to further determine the sites of action of SV-PLA2 on the hypothalamo-pituitary-adrenal (HPA) axis function and on the release of the pathognomonic cytokine, tumor necrosis factor alpha (TNF alpha), of different types of inflammatory stress. Our results indicate that SV (25 microg/animal) and PLA2 (5 microg/animal), from the same origin, stimulate the HPA and immune axes when administered (i.p.) to adult mice; both preparations were able to enhance plasma glucose, ACTH, corticosterone (B), and TNF alpha plasma levels in a time-related fashion. SV was found to activate CRH- and arginine vasopressin-ergic functions in vivo and, in vitro, SV and PLA2 induced a concentration-related (0.05-10 microg/ml) effect on the release of both neuropeptides. SV also was effective in changing anterior pituitary ACTH and adrenal B contents, also in a time-dependent fashion. Direct effects of SV and PLA2 on anterior pituitary ACTH secretion also were found to function in a concentration-related fashion (0.001-1 microg/ml), and the direct corticotropin-releasing activity of PLA2 was additive to those of CRH and arginine vasopressin; the corticotropin-releasing activity of both SV and PLA2 were partially reversed by the specific PLA2 inhibitor, manoalide. On the other hand, neither preparation was able to directly modify spontaneous and ACTH-stimulated adrenal B output. The stimulatory effect of SV and PLA2 on in vivo TNF alpha release was confirmed by in vitro experiments on peripheral mononuclear cells; in fact, both PLA2 (0.001-1 microg/ml) and SV (0.1-10 microg/ml), as well as concavalin A (1-100 microg/ml), were able to stimulate TNF alpha output in the incubation medium. Our results clearly indicate that PLA2-dependent mechanisms are responsible for several symptoms of inflammatory stress induced during neurotoxemia. In fact, we found that this particular PLA2-related SV is able to stimulate both HPA axis and immune functions during the acute phase response of the inflammatory processes.
 ...
PMID:A phospholipase A2-related snake venom (from Crotalus durissus terrificus) stimulates neuroendocrine and immune functions: determination of different sites of action. 944 33

Pneumolysin-deficient mutant strains of Streptococcus pneumoniae are known to cause less-severe sepsis than wild-type pneumococcal strains that produce pneumolysin. This difference is associated with greater host resistance in mice infected with the pneumolysin-deficient strains. These studies show that the host resistance developed during the first 1 to 2 days after infection with a pneumolysin-deficient mutant strain is dependent on tumor necrosis factor alpha but is apparently independent of interleukin 1beta (IL-1beta) or IL-6. Survival beyond 5 days appeared to depend on the ability of the mice to produce IL-1beta.
 ...
PMID:Role of tumor necrosis factor alpha in the host response of mice to bacteremia caused by pneumolysin-deficient Streptococcus pneumoniae. 945 52

Heparin induced extracorporeal lipoprotein fibrinogen precipitation (HELP) is an established procedure for removal of low-density lipoprotein (LDL) cholesterol, lipoprotein (a), and fibrinogen in patients with severe hypercholesterolemia. In vitro studies revealed that HELP also removes endotoxin, tumor necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP). With the intention to treat, we applied this procedure to 4 patients with severe gram-negative sepsis with highly elevated endotoxin blood levels. Nine treatments were performed, 6 using the standard HELP precipitating buffer and 3 without addition of heparin to the precipitating buffer. Heparin was omitted from the precipitating buffer to avoid fibrinogen depletion in patients at risk (low fibrinogen, postoperative). The average processed plasma volume was 3,386 ml in the standard and 2,963 ml in the modified treatment. Mean reductions (%) in plasma solute concentrations were (standard/ modified procedure) as follows: endotoxin, 50/57; TNF-alpha, 25/5; CRP, 49/55; fibrinogen, 49/6; total cholesterol, 38/5; and apolipoprotein B (Apo B), 41/2. Both treatment modalities were equally effective in removing endotoxin and CRP. With the modified precipitation buffer, fibrinogen was not removed. To further simplify the extracorporeal treatment, we have designed a closed-loop circuit with 2 adsorbers in series, one for removal of TNF-alpha (dextran sulfate modified cellulose) and the other for removal of endotoxin (DEAE-cellulose). In vitro evaluation confirmed very efficient endotoxin and TNF-alpha removal from plasma. This system is very simple, operates at physiological pH, and uses adsorbers already in clinical use for other purposes.
 ...
PMID:HELP apheresis in the treatment of sepsis. 945 25

The time sequence and the mechanisms leading to the development of the hypertriglyceridemia of bacteremic sepsis are not fully understood. This study was conducted to determine the mechanisms leading to the early rise in serum triglycerides (TG). Bacteremic sepsis was induced in fasted and parenterally fed rats by intravenous infusion of live Escherichia coli colonies over a 1 h period every 24 h up to 96 h. Body temperature was elevated from 12 to 48 h after E. coli infusion in fasted rats and from 24 to 72 h after E. coli infusion in fed rats. The initial rise in serum TG was observed at 3 h after E. coli infusion; in fasted rats this elevation was maintained over 72 h. In the parenterally fed rats, hypertriglyceridemia was evident only at the 3 h time point. Serum concentrations of tumor necrosis factor alpha (TNF-alpha) were elevated significantly at 60 min after initiating the E. coli infusion, peaked at 90 min, and declined by 120 min. Immunization with neutralizing goat anti-TNF-alpha IgG did not block the initial increase in serum TG induced by E. coli. This early rise in TG in fasted E. coli-treated rats was accompanied by a 33% increase in TG secretion in comparison with control rats. TG secretion declined by 27% at 9 h and remained depressed at 12 and 24 h in comparison with time-matched control rats. By 24 h lipid accumulation was evident in the livers of the fasted and fed E. coli-treated rats. Most of the fasted E. coli-treated rats died by 72 h. Parenteral feeding extended survival of E. coli-treated rats until 120 h. These findings along with the observation that two mechanisms are involved in maintaining the elevation of serum TG during E. coli sepsis suggests that the hypertriglyceridemia may be important in host survival.
 ...
PMID:Sequential alterations in tissue lipoprotein lipase, triglyceride secretion rates, and serum tumor necrosis factor alpha during Escherichia coli bacteremic sepsis in relation to the development of hypertriglyceridemia. 946 73

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.
 ...
PMID:Endotoxin removal by polymyxin-B immobilized polystyrene-derivative fibers during in vitro hemoperfusion of 10% human plasma. 946 2


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