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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The kinetics of cytokine release and acute-phase protein gene expression in liver were investigated in rats receiving a single intraperitoneal bolus dose of Escherichia coli lipopolysaccharide (LPS). Transient elevation of plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were detected. Hepatic messenger RNAs for two acute-phase proteins, alpha 1-acid glycoprotein and alpha 2-macroglobulin, were measured by Northern blotting and were found to increase to a maximum at 24 h, returning to normal by 72 h; plasma concentrations showed a slower but more sustained rise. For albumin, hepatic mRNA was reduced, being minimum at 24 h with a similar but more prolonged fall in plasma concentration. Pretreatment of rats with TNF-alpha monoclonal antibody 4 h before LPS ameliorated weight loss and anorexia, partially suppressed the rise in IL-6 and reduced the increase in hepatic mRNA and plasma concentrations of alpha 1-acid glycoprotein and alpha 2-macroglobulin. For albumin, however, such pretreatment had no effect on the fall in either hepatic mRNA or plasma concentration. Thus we have defined an in vivo role of TNF-alpha in the control of endotoxin-induced acute-phase protein generation.
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PMID:Kinetics of endotoxin-induced acute-phase protein gene expression and its modulation by TNF-alpha monoclonal antibody. 137 42

Endotoxin, a lipopolysaccharide (LPS), is a bacterial cell wall product instrumental in producing deleterious host responses to infection. This LPS appears to act, in part, by triggering release of endogenous mediators such as cytokines. Repeated exposures to endotoxin produce attenuated responses to this molecule. To examine the mechanisms and biologic consequences of this tolerance to LPS, Wistar rats were subjected to a 14-day course of LPS administration. Tolerance to LPS with regard to anorexia, weight loss, and acute-phase responses was noted. Attenuation of these physiologic responses was accompanied by abrogation of circulating cytokine appearance in response to endotoxin, suggesting that tolerance to LPS is in part due to a decreased production of cytokines. Tolerance to LPS also diminished the response to a subsequent infected thermal injury, as measured by food intake, body weight, fibrinogen levels, and mortality. Thus, clinical conditions involving repeated exposure to LPS may modify the host's responses to subsequent injury. The attenuated responses to injury accompanying the decreased production of cytokines further implicate cytokines in the pathogenesis of injury and disease.
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PMID:Tolerance to endotoxin prevents mortality in infected thermal injury: association with attenuated cytokine responses. 156 35

To determine whether the cytokine tumor necrosis factor/cachectin might be a mediator of hepatotoxicity seen after exposure to polyhalogenated aromatic hydrocarbons, rats treated with a single dose of 3,3',4,4'-tetrabromobiphenyl (150 mumol/kg intraperitoneally) or corn oil vehicle were studied. The 3,3',4,4'-tetrabromobiphenyl caused the expected anorexia, alterations in organ weights and changes in cytochromes P-450 over 21 days. Although tumor necrosis factor could not be detected in the serum of rats at any time after 3,3',4,4'-tetrabromobiphenyl treatment alone (from 90 min to 21 days), 3,3',4,4'-tetrabromobiphenyl treatment significantly increased peak serum tumor necrosis factor concentrations after intravenous bacterial endotoxin (lipopolysaccharide, 1 mg/kg). This effect was seen with lipopolysaccharide given 24 hr, 48 hr, and 20 days after 3,3',4,4'-tetrabromobiphenyl treatment and increases in peak serum tumor necrosis factor levels ranged from threefold to eightfold over controls in various experiments with no significant differences between the three time points. However, a synergistic increase in hepatic damage (assessed by serum enzymes and liver histological findings 24 hr after lipopolysaccharide injection) was seen in rats given lipopolysaccharide 24 hr and 48 hr after 3,3',4,4'-tetrabromobiphenyl administration, with 75% and 25% lethality, respectively. There was no lethality with lipopolysaccharide given 20 days after 3,3',4,4'-tetrabromobiphenyl administration or with simultaneous administration. A lower dose of lipopolysaccharide (0.1 mg/kg) given 24 hr after 3,3',4,4'-tetrabromobiphenyl also enhanced hepatotoxicity and serum tumor necrosis factor but without lethality. Lipopolysaccharide decreased cytochromes P-450 concentrations and activities to similar extents at all time points tested in both control and 3,3'4,4'-tetrabromobiphenyl-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:3,3',4,4'-Tetrabromobiphenyl sensitizes rats to the hepatotoxic effects of endotoxin by a mechanism that involves more than tumor necrosis factor. 166 20

1. We have studied the time course of the numbers of arterial monocytes and their superoxide anion (O2-) production in a chronically instrumented sheep model of subacute endotoxaemia induced by a continuous intravenous infusion of Escherichia coli lipopolysaccharide (20 ng min-1 kg-1). 2. Four out of 11 animals died from irreversible respiratory and cardiovascular failure within 21 h of the start of lipopolysaccharide administration ('non-survivors'), whereas in the seven surviving sheep ('survivors') there was a persistence of decreased systemic vascular resistance, systemic hypotension, pulmonary hypertension, anorexia and lethargy. 3. O2- generation by isolated monocytes was measured by the O2- dismutase-inhibitable reduction of ferricytochrome c after stimulation with phorbol myristate acetate (100 ng/ml) or opsonized zymosan (3 mg/ml). Basal mean value of phorbol myristate acetate-stimulated O2- production was significantly (P = 0.008) higher for non-survivors (31.3 +/- 8.8 nmol 30 min-1 10(-6) cells; n = 4) than for survivors (6.2 +/- 2.3 nmol 30 min-1 10(-6) cells; n = 7). 4. For both survivors and non-survivors, monocyte counts and phorbol myristate acetate-stimulated O2- production increased over time to reach in survivors a plateau after 2 days of continuous lipopolysaccharide infusion. Similar results were obtained when monocytes were stimulated for O2- production with opsonized zymosan. 5. These results suggest that (1) increased O2- production by monocytes and monocytosis appear with a precise, delayed time course during the development of subacute endotoxaemia in sheep; and (2) a high stimulated O2- production by monocytes before lipopolysaccharide administration may represent a predictive factor for the subsequent respiratory failure and outcome of endotoxaemia.
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PMID:Superoxide production by peripheral blood monocytes during sustained endotoxaemia in sheep. 166 89

The present study was designed to test whether a tolerance to the hypophagic effects of bacterial lipopolysaccharide (LPS) and muramyl dipeptide (MDP) develops with repeated injections in rats and whether a relationship between the hypophagic effects of both compounds exists. Only the first of three subsequent intraperitoneal injection of LPS (100 micrograms/kg body wt each), given every 2nd day, led to a significant reduction of food intake. In contrast, MDP (1.6 mg/kg body wt) did not lose its hypophagic effect with four subsequent intraperitoneal injections. Furthermore, the LPS tolerance did not alter the hypophagic response to subsequently injected MDP. Likewise, MDP pretreatment did not alter the hypophagic response to LPS. Doses of MDP and LPS that were individually below the threshold for a reliable reduction of food intake (0.4 mg MDP/kg body wt + 25 micrograms LPS/kg body wt) reduced food intake synergistically when injected together. The hypophagia produced by combined injections of MDP plus LPS slowly diminished with repeated injections. The results indicate that separate but interacting mechanisms are involved in the feeding responses to MDP and LPS. The observed synergism between MDP and LPS suggests a synergistic role of bacterial muramyl peptides and LPS in the anorexia during bacterial infections.
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PMID:Differential feeding responses to bacterial lipopolysaccharide and muramyl dipeptide. 188 52

Long periods in space may expose astronauts to the potentially harmful effects of ionizing radiation. We have used a primate model to evaluate any role of lipopolysaccharide (LPS, endotoxin) in radiation sickness. Vervet monkeys, which had been whole-body 60Co irradiated with an LD100 exposure, had periodic blood samples taken for the determination of LPS, anti-LPS IgG antibodies and bacteriological studies. On day 2 post-irradiation, primates were treated i.m. with either sterile 0.9% saline, or equine anti-LPS hyperimmune plasma (Anti-LPS), or orally with tripotassium-dicitrato-bismuthate ("Denol"). Gram positive bacteria were evident in blood samples of all animals as early as 2 d post-irradiation. Gram negative bacteria were found in the blood of saline- and Denol-treated primates by days 5 and 8, respectively, but first appeared on day 13 in the anti-LPS-treated animals. The saline controls and Denol-treated animals showed insignificant rises in plasma LPS on day 3, which increased further thereafter achieving significance on day 8 (p less than 0.01). These elevated levels persisted until death. However, in anti-LPS-treated monkeys, LPS concentrations remained below baseline until day 9, after which they rose significantly until death, but, were significantly less than the concentrations in both other groups (p less than 0.001). The anti-LPS-treated animals survived significantly longer than both the other groups (p less than 0.005). Since LPS may cause nausea, vomiting, diarrhea, anorexia and headaches, Anti-LPS administration may be of value in reducing plasma LPS concentration in humans and improving their performance and survivability.
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PMID:Anti-LPS antibodies reduce endotoxemia in whole body 60Co irradiated primates: a preliminary report. 224 44

For further characterization of the mechanism involved in the anorexia during bacterial infection, we investigated whether muramyl dipeptide (MDP), the minimal immunologically active structure of gram-positive bacterial cell walls, affects rats' food intake in the same way as lipopolysaccharide (LPS) from E. coli. MDP (1.6 mg/kg body weight = b.wt.) injected intraperitoneally (IP) reduced food intake by decreasing meal frequency without affecting meal size. Indomethacin (2.5 mg/kg b.wt., IP) but not verapamil (5 mg/kg b.wt., IP) attenuated the hypophagic effect of MDP. In further experiments, MDP and LPS (100 micrograms/kg b.wt., IP) both inhibited gastric emptying and indomethacin failed to block this effect of LPS. Hepatic vagotomy did not attenuate the hypophagic effects of MDP or LPS. LPS reduced water intake only when food was available, but reduced food intake also during water deprivation. MDP did not affect water intake. MDP and LPS both had an aversive effect, but LiCl, which was also aversive, failed to reduce feeding under the conditions tested. This questions the role of a conditioned taste aversion in the hypophagia induced by MDP or LPS. The results suggest that a stimulation of eicosanoid synthesis contributes to MDP-induced hypophagia and may therefore also contribute to the anorexia during infection. In contrast, an inhibition of gastric emptying, an activation of hepatic satiety signals or a reduction of water intake, does not seem to be crucial for the hypophagic effects of MDP or LPS.
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PMID:Comparison of the effects of bacterial lipopolysaccharide and muramyl dipeptide on food intake. 238 34

To characterize the mechanism of the anorexia during infection, we investigated the effect of E. coli lipopolysaccharide (LPS) on feeding in rats under various conditions: LPS (125, 100, 75, and 50 micrograms/kg body weight = b. wt.) injected intraperitoneally (IP) reduced food intake by decreasing meal frequency without affecting meal size. The Ca++-channel blocker verapamil (5 mg/kg b. wt., IP) or the antipyretic and antiphlogistic drug indomethacin (2.5 mg/kg b. wt., IP), but not combined alpha- and beta-adrenergic receptor blockade by IP phentolamine plus propranolol (500 micrograms/kg b. wt., each) attenuated the anorectic effect of LPS (125 or 100 micrograms/kg b. wt.). The results suggest that a phospholipase A2-sensitive mechanism contributes to the anorexia during injection.
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PMID:Verapamil and indomethacin attenuate endotoxin-induced anorexia. 269 50

Macrophage secretory products are suspected to participate in the severe lean tissue wasting related to chronic illness. The protein metabolic effects of chronic, 7-day cachectin/tumor necrosis factor (cachectin) or interleukin 1 alpha (IL-1 alpha) administration in vivo were studied in male Wistar rats that were 1) freely fed, 2) pair fed, 3) total protein and calorie starved, 4) twice daily lipopolysaccharide (LPS) administered, 5) twice daily cachectin administered, and 6) twice daily IL-1 alpha administered. LPS, cachectin, or IL-1 alpha administration produced anorexia; weight loss in these groups was comparable to respective pair-fed animals. However, LPS, cachectin, or IL-1 alpha accelerated peripheral protein wasting while preserving liver protein content, unlike the pattern in the pair-fed or starved animals in which loss of liver proteins and relative preservation of skeletal muscle protein were observed. The decrease in skeletal muscle protein content in LPS- or cytokine-treated animals was associated with coordinate decreases in muscle mRNA levels for the myofibrillar proteins myosin heavy chain, myosin light chain, actin, and in the 18S and 28S subunits of ribosomal RNA. We conclude that chronic exposure to the cytokines, IL-1 alpha or cachectin, can simulate those body and muscle protein changes seen in experimental LPS administration or chronic disease and markedly differ from the pattern of protein redistribution due to caloric restriction.
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PMID:Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins. 278 90

It has recently been demonstrated by three independent research groups including ours that interleukin 1 (IL-1), a polypeptide hormone produced by activated monocytes or macrophages, or both, stimulates the release of hypothalamic corticotropin-releasing factor (CRF). Since CRF acts centrally in the brain to reduce food intake, we hypothesized that IL-1 might induce anorexia through this central action of CRF. The present study was carried out to examine the hypothesis, using male Wistar rats. Based on three lines of evidence, we report here that IL-1, both endogenously released and exogenously administered, induces the suppression of food intake in rats and that endogenous CRF in the brain is involved in the IL-1-induced anorexia. First, lipopolysaccharide (LPS), a potent stimulant of the release and production of endogenous IL-1, caused anorexia in a dose-related manner, and this effect was significantly blocked by pretreatment with glucocorticoid hormones, which have been shown to inhibit the production of endogenous IL-1 by LPS. Second, intraperitoneal injection of IL-1 resulted in a dose-related suppression of food intake. Third, anorexia induced by IL-1 was diminished by the immunoneutralization of endogenous CRF in the brain. These results provide further evidence of the existence of bidirectional communication between the immune and neuroendocrine systems. Furthermore, this connection between IL-1 and CRF may represent a mechanism by which anorexia results from the activation of the immune system by such immunological challenges as acute infectious diseases.
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PMID:Anorexia induced by interleukin 1: involvement of corticotropin-releasing factor. 278 77


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