Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to determine the effects of halothane on rat cell-mediated immune function, rats were exposed to 1% halothane for up to 5 hours. Immediately, 24 hours or 48 hours following anesthesia, rat lymphocytes from the spleen were analyzed for their ability to respond to the mitogens phytohemagglutinin (PHA), pokeweed mitogen (PWM), concanavalin A (ConA) and lipopolysaccharide (LPS). In addition, percentages of lymphocyte subpopulations in the spleen were assessed as well as ability of the lymphocytes to express specific receptors. Extended periods of halothane anesthesia (5 hours) suppressed the ability of the lymphocytes to respond to the mitogen PHA immediately following anesthesia. Twenty-four hours later, proliferative responses to the mitogens PHA, PWM and ConA were significantly reduced. However, by 48 hours following treatment, proliferative responses were normal. Halothane did not alter proliferative responses to the mitogen LPS. Prolonged anesthesia (5 hours) also increased the percentage of T and CD8+ (cytotoxic) lymphocytes in the spleen, although for less than 24 hours. The ability of T lymphocytes to express both the CD8 and CD25 (IL-2) receptors in response to PHA were suppressed. These results suggest that halothane suppresses rat T cell function, perhaps through suppression of IL-2 receptor expression.
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PMID:Halothane inhibits T cell proliferation and interleukin-2 receptor expression in rats. 877 74

Cytokines and eicosanoids are well documented important mediators of endotoxemia. Bicyclic imidazoles are a novel class of nonsteroidal anti-inflammatory compounds that display unique pharmacological profiles by reducing cytokine production and arachidonic acid metabolism. In this study, we evaluated the ability of the bicyclic imidazole, SK&F 86002, to attenuate endotoxin-induced cardiopulmonary dysfunction. Pigs were randomly assigned to one of four groups: LPS (n = 5), given .5 microgram/kg/h 055:B5 Escherichia coli lipopolysaccharide (LPS) intravenously (i.v.) for 6 h; saline (n = 5); SK&F 86002 (n = 3), given 50 mg/kg SK&F 86002 orally 30 min prior to anesthesia; and SK&F 86002 + LPS (n = 5). Administration of LPS resulted in cardiopulmonary dysfunction characterized by decreased stroke volume and arterial oxygen tension, and increased room air alveolar-arterial oxygen gradient, pulmonary arterial pressure, pulmonary vascular resistance, and peak intratracheal pressure. Additionally, LPS administration was associated with leukopenia and increased pulmonary myeloperoxidase activity. Pretreatment with SK&F 86002 attenuated LPS induced hypotension, hypoxemia and bronchoconstriction and blocked the pulmonary hypertension. SK&F 86002 blocked the LPS-induced increase in myeloperoxidase activity, indicating a reduction in pulmonary neutrophil infiltration, but had no effect on systemic leukopenia. Pretreatment with SK&F 86002 significantly attenuated LPS-induced increases in plasma thromboxane B2 and tumor necrosis factor-alpha. We hypothesize that ameliorating effects of SK&F 86002 in this endotoxin model of cardiopulmonary dysfunction are related to inhibition of cytokine and eicosanoid biosynthesis.
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PMID:SK&F 86002, a dual cytokine and eicosanoid inhibitor, attenuates endotoxin-induced cardiopulmonary dysfunction in the pig. 894 52

The aim of this study was to monitor plasma interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) levels in patients subjected to cardiac surgery under general anesthesia. In addition, proliferation of peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA) and the ability of these cells to secrete lipopolysaccharide-induced IL-6 and TNF-alpha during the observation period was investigated. IL-6 and TNF-alpha levels were measured using bioassays. We found that despite high variability in the postoperative response of the patients, characteristic kinetics in the appearance of the cytokines in plasma could be demonstrated. Most significant phenomenon was an increase of IL-6 level 1 day after operation associated with an inhibition of TNF-alpha concentration. Relatively high, preoperative concentrations of these cytokines were probably elicited by stress. Control, healthy donors, did not exhibit measurable levels of these cytokines. In terms of proliferative response of PBMC to PHA and of cytokine production in vitro, the patients could be classified into low and high responding. The proliferative response of PBMC from low responders was progressively increasing and the response of high responders did not exhibit meaningful changes throughout the observation period. PBMC from low producers of IL-6 showed also an increased ability to secrete this cytokine during the monitoring time while the cells from high producers yielded less IL-6 on the last day of the follow up. Regarding TNF-alpha production, PBMC from low responders reacted strongly by secretion of this cytokine on day 1 after surgery in contrast to high responders whose cells yielded less TNF-alpha after surgery. In majority of cases TNF-alpha production had a tendency to diminish on the last day of observation. We conclude that the changes in cytokine levels as well as an altered reactivity of PBMC in vitro reflect the immune response to the postoperative trauma and are desirable for a normal course of the immune response and wound healing.
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PMID:Immunological status of patients subjected to cardiac surgery: serum levels of interleukin 6 and tumor necrosis factor alpha and the ability of peripheral blood mononuclear cells to proliferate and produce these cytokines in vitro. 901 62

Anesthetic agents are believed to have an adverse effect on human immune defense mechanisms. We investigated changes in peripheral immune cell numbers such as natural killer (NK) cells, B cells, and T lymphocyte subpopulations (CD4+ and CD8+ cells) and differences in cytokine production after stimulation with different mitogens before and during narcosis. We studied 30 patients undergoing elective orthopedic surgery. Stimulatory experiments were performed with the mitogens lipopolysaccharide, phytohemagglutinin A, and inactivated Newcastle disease virus. During general anesthesia with fentanyl, thiopental, and isoflurane, there was a significant decrease of circulating NK cells in the peripheral blood accompanied by a significant increase of B cells and CD8+ T lymphocytes. We detected a significant anesthesia-associated increase of interferon (IFN)-gamma, IFN-alpha, tumor necrosis factor-alpha, and soluble interleukin-2 receptor (sIL-2R) synthesis after stimulation with different mitogens while interleukin (IL)-1 beta and IL-6 protein did not change significantly. After the beginning of surgery, CD8-positive cells showed a return to control values and NK cell number increased slightly. These findings suggest that general anesthesia interferes with immune cell number and immune cell response. This may explain the clinically well-recognized disturbance of human immunity after surgery and general anesthesia.
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PMID:The effects of general anesthesia on human peripheral immune cell distribution and cytokine production. 914 81

Because Kupffer cells constitute the largest fixed macrophage population and reside at a strategic position in hepatic sinusoids, interacting with hepatocytes, circulating cells, and mediators from the gut, they may be important in the inflammatory response after injury. This study examined the effect of remote tissue injury on Kupffer cell function. Femurs of Sprague-Dawley rats were fractured under anesthesia. Subsequently, their livers were perfused for measurement of oxygen consumption and the isolation and culture of Kupffer cells. At 2 and 48 h after femur fracture, hepatic oxygen consumption increased 17 and 19%, respectively. Gadolinium chloride pretreatment to ablate Kupffer cells blocked this increase of hepatic oxygen consumption after femur fracture but had no effect in sham-operated animals. In Kupffer cells isolated and cultured 2 h after femur fracture, superoxide formation stimulated by phorbol ester increased eightfold, phagocytosis increased fourfold, and lipopolysaccharide (LPS)-stimulated prostaglandin E2 increased sixfold in comparison to sham-operated controls. In contrast, LPS-stimulated tumor necrosis factor-alpha and nitric oxide production decreased 50 and 60%, respectively. These data show that peripheral trauma rapidly induces changes in hepatic macrophages characterized by adaptation to a more antimicrobial and less proinflammatory phenotype.
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PMID:Adaptive Kupffer cell alterations after femur fracture trauma in rats. 922 82

We previously showed that a febrile dose of lipopolysaccharide (LPS) in rats resulted in induction of cyclooxygenase-2 (COX-2) mRNA in brain blood vessels/leptomeninges and telencephalic neurons. To elucidate the causal link between fever and LPS-induced COX-2 mRNA, we experimentally modified one or the other of these parameters and examined their relation. 1) LPS-induced fever was suppressed by pretreatment with a COX-2-specific inhibitor. 2) Levels of COX-2 mRNA in the neurons and blood vessels 2.5 h after LPS administration were even higher in the inhibitor-pretreated rats (afebrile) than in vehicle-pretreated ones (febrile). 3) After repeated administration of LPS, rats became tolerant to LPS, in which state LPS induced neither fever nor COX-2 mRNA in blood vessels/leptomeninges. When rats had not completely established LPS tolerance, they showed various degrees of fever that were closely correlated with the level of COX-2 mRNA in blood vessels but not with that in neurons. 4) Urethan anesthesia reduced basal as well as LPS-induced COX-2 mRNA in telencephalic neurons, but the rats still responded to LPS with fever and induction of COX-2 mRNA in the blood vessels/leptomeninges. These results suggest that COX-2 induced in brain blood vessels/leptomeninges is involved in the molecular mechanism of LPS-induced fever.
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PMID:Involvement of cyclooxygenase-2 in LPS-induced fever and regulation of its mRNA by LPS in the rat brain. 922 82

Nitric oxide (NO) is an important biological messenger involved in the regulation of blood vessel tone, neurotransmission, inflammatory responses, and host defenses. Inhalational anesthetics have been shown to inhibit the function of the NO signaling pathway in a variety of tissues. In addition, acute inhibition of the NO signaling pathway significantly reduced the required alveolar concentration of halothane or isoflurane for anesthesia, which suggests a role for the NO signaling pathway in mechanisms of anesthesia and consciousness. We now report that inhalational anesthetics affect gene expression of nitric oxide synthases (NOS) (EC 1.14.13.39), the enzymes that synthesize NO from L-arginine. Both halothane and isoflurane, at clinically relevant concentrations, significantly up-regulate the mRNA, protein, and activity level of NOS in lipopolysaccharide-treated macrophages (inducible NOS; type II NOS), and bovine pulmonary endothelial cells (endothelial constitutive NOS; type III NOS). This is a novel interaction between inhalational anesthetics and the NO signaling pathway and has wide-ranging implications for both clinical medicine and experimental biology.
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PMID:Inhalational anesthetics up-regulate constitutive and lipopolysaccharide-induced inducible nitric oxide synthase expression and activity. 938 23

In chronic experiments on rats pretreated with bilateral microinjection of 25 nl 1% capsaicin to the caudal ventrolateral medulla under ketamine-xylazine-acepromazine anesthesia, an enhancement of the temperature response to intraperitoneal application of 3 microg/kg E. coli lipopolysaccharide as compared to animals who received vehicle to the caudal ventrolateral medulla was found. This is indicative of the involvement of the capsaicin-sensitive bulbar structures in thermoregulatory processes during endotoxemia.
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PMID:Are the capsaicin-sensitive structures of ventral medulla involved in the temperature response to endotoxin in rats? 957 98

Previous work has shown that pre-treatment with the thrombin inhibitor recombinant desulfato-hirudin prevented fibrin formation and respiratory dysfunction in porcine lipopolysaccharide shock. We examined the effects of delayed administration of recombinant desulfato-hirudin in bacterial lipopolysaccharide shock. Miniature pigs were studied under anaesthesia and ventilation, and received a bacterial lipopolysaccharide infusion (2 microg/kg/h) for 7 h; recombinant desulfato-hirudin was started 1 h after bacterial lipopolysaccharide in 10 animals (bolus 12.9 nmol/kg; continuous infusion 6.5 nmol/ kg/h); 10 randomised control animals received saline instead of recombinant desulfato-hirudin. Fibrin and thrombin-antithrombin complex levels in plasma were significantly lower in bacterial lipopolysaccharide+recombinant desulfato-hirudin animals than in controls. Both groups displayed a similar rise in pulmonary vascular resistance and other parameters of lung dysfunction; only lung tissue wet/dry ratio was lower in recombinant desulfato-hirudin-treated than in control animals. Both groups had similar circulatory alterations. Recombinant desulfato-hirudin interrupted coagulation activation during ongoing bacterial lipopolysaccharide-induced shock in pigs even when administered with a delay of one hour after start of the bacterial lipopolysaccharide infusion. A protective effect of delayed recombinant desulfato-hirudin administration on bacterial lipopolysaccharide-induced acute lung injury and alterations in the systemic circulation could not be demonstrated in this experiment.
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PMID:Delayed treatment with desulfato-hirudin prevents fibrin formation in lipopolysaccharide-induced shock. 961 Sep 58

Sexual dimorphism exists in the immune response. Both humoral and cell-mediated immunity are more active in females than in males, and steroid gonadal hormones may play an important role in regulating this response. We have documented gender differences in several aspects of neutrophil and macrophage functions elicited by lipopolysaccharide (LPS) (endotoxin) treatment and/or acute ethanol intoxication. In LPS-treated female rats, circulating neutrophils and alveolar macrophages are resistant to the deleterious effects of surgery and anesthesia on phagocytosis observed in male rats. The generation of cytokine-induced neutrophil chemoattractant (CINC) by hepatocytes and Kupffer cells of LPS-treated rats, as well as TNF-alpha secretion by Kupffer cells and alveolar macrophages of acutely ethanol intoxicated rats are also gender dependent. The effects of alcohol on the immune response are expressed differently in males and females. In LPS plus ethanol-treated rats gender differences were noted in terms of adhesion molecule (CD11b/c) expression on circulating neutrophils, and cytoskeletal reorganization in blood-recruited neutrophils and Kupffer cells. Nitric oxide (NO) plays an important role in inflammatory processes. We found gender differences in NO production by alveolar macrophages of LPS-treated rats; this difference was abrogated by ethanol treatment. LPS tolerance and ethanol treatment modulate hepatic NO production in rats in a cell- and gender-dependent fashion, which may exert a protective influence against oxidative injury in the female liver.
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PMID:Gender differences in some host defense mechanisms. 1045 17


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