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)

Several inflammatory cytokines, most notably tumor necrosis factor (TNF) and IL-1, induce anorexia and loss of lean body mass, common manifestations of acute and chronic inflammatory conditions. In C57BL/6 female mice, the administration of TNF, IL-1, and, to a lesser extent, leukemia inhibitory factor (LIF), produced a prompt and dose-dependent increase in serum leptin levels and leptin mRNA expression in fat. IL-10, IL-4, ciliary neurotrophic factor, and IL-2, cytokines not known to induce anorexia or decrease food intake, had no effect on leptin gene expression or serum leptin levels. After administration of Escherichia coli lipopolysaccharide (LPS), leptin gene expression and leptin levels were increased. These findings suggest that leptin levels may be one mechanism by which anorexia is induced during acute inflammatory conditions.
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PMID:Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia. 899 53

This study examined the role of the interleukin-1 (IL-1) type I receptor (IL-1RtI) in the acute phase response (APR) to inflammation in mice. Turpentine (100 microliters/mouse) injected subcutaneously induced fever, lethargy, body weight loss, and anorexia in IL-1RtI wild-type mice. Knockout mice lacking the IL-1RtI were resistant to these effects of turpentine, supporting a role for this receptor in the APR to local inflammation. The intraperitoneal injection of a low (50 micrograms/kg) or high (2.5 mg/kg) dose of lipopolysaccharide (LPS) induced similar APRs in IL-1RtI wild-type and knockout mice. IL-1RtI knockout mice were resistant to the APR induced by peripherally injected murine IL-1 beta, suggesting that it is not the interaction of endogenous IL-1 beta with IL-1RtII that induces an APR to LPS in these mice. We speculate that the absence of IL-1RtI in these knockout mice results in the sensitization of other cytokine pathways to mediate the APR to LPS.
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PMID:IL-1 type I receptor mediates acute phase response to turpentine, but not lipopolysaccharide, in mice. 899 68

1. Glutathione concentrations in liver and lung fall when food intake or sulphur amino acid intake is inadequate. However, concentrations may be restored during inflammation, despite anorexia, provided that prior sulphur amino acid intake is adequate. 2. We studied the mechanisms of these changes by measuring the effect of sulphur amino acid and protein intake on hepatic glutathione synthesis and gamma-glutamylcysteine synthetase activity, hepatic and lung glutathione concentrations, glutathione reductase and glutathione peroxidase activities in young rats given an inflammatory challenge by intraperitoneal injection of tumour necrosis factor-alpha or endotoxin (lipopolysaccharide). 3. Diets containing 200 g of casein and 8 g of L-cysteine/kg (normal-protein diet), or 80 g of casein and 8 g of L-cysteine, or isonitrogenous amounts of L-methionine or L-alanine (low-protein diets) were fed ad libitum to young Wistar rats for 8 days. Dietary groups were subdivided into three: one subgroup continued feeding ad libitum, a second was given tumour necrosis factor or lipopolysaccharide and killed 24 h thereafter, while the third was pair-fed to the intakes of the second subgroup for 24 h before being killed. 4. Glutathione concentrations in liver and lung were reduced in rats fed the low-protein diet containing alanine, and in all dietary groups when food intake was restricted. The inflammatory challenges restored hepatic glutathione concentrations in all groups but the diet supplemented with alanine, which had an inadequate sulphur amino acid content. In lung, restoration occurred only in animals fed the normal-protein diet. 5. The activity of gamma-glutamylcysteine synthetase, which is rate limiting for glutathione synthesis, was unaffected by dietary or sulphur amino acid intake or by the inflammatory response. Substrate supply may therefore be a major determinant in glutathione synthesis in vivo. 6. Total hepatic glutathione synthesis was affected by food intake, the type and amount of sulphur amino acids in the diet and by inflammation. Total synthesis was 207, 137, 421 and 90 mumol/day for animals fed ad libitum the normal-protein diet, or low-protein diets supplemented with cysteine, methionine or alanine respectively, ad libitum. Pair-feeding resulted in values of 76, 31, 71, and 0 mumol/day respectively. After lipopolysaccharide injection, rates increased to 200, 117, 151 and 56 mumol/day respectively. 8. Reductase and peroxidase activities increased in liver and lung, when low-protein diets which contained supplemental methionine or alanine were consumed ad libitum. A reduction in food intake resulted in enzyme activity changes, which suggested that recycling of glutathione increased in lung and decreased in liver. Injection of tumour necrosis factor reversed this effect. 9. The restoration of glutathione concentrations in liver after an inflammatory challenge is closely associated with an enhanced rate of synthesis and increased recycling. The former is impaired when inadequate sulphur amino acid is consumed before the challenge. In lung, increased recycling of glutathione may help maintain concentrations when food intake is restricted, but not during inflammation.
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PMID:Dietary sulphur amino acid adequacy influences glutathione synthesis and glutathione-dependent enzymes during the inflammatory response to endotoxin and tumour necrosis factor-alpha in rats. 909 11

We tested the hypothesis that increased dietary fish oil levels (via modulation of the production of inflammatory mediators) modulate sickness symptoms (i.e., anorexia, cachexia, fever, lethargy) of systemic and local inflammation. Swiss Webster mice were implanted with biotelemeters to measure body temperature and motor activity and were fed a diet high in n-3 fatty acids (17% wt/wt menhaden oil) or a reference diet (17% wt/wt hydrogenated coconut oil or normal rodent chow) for 6 wk. Local inflammation was induced by subcutaneous injection of turpentine (100 microl/mouse). Systemic inflammation was elicited by intraperitoneal injection of lipopolysaccharide (LPS; 2.5 mg/kg). Fever, lethargy, anorexia, and weight decrease during turpentine abscess were all inhibited (P < 0.05) in mice fed the fish oil diet. Indomethacin, similar to the fish oil diet, attenuated the turpentine-induced symptoms in mice fed a normal diet. Dietary n-3 fatty acids prevented fever and attenuated the decrease in body weight caused by LPS but did not affect the LPS-induced lethargy and anorexia. Within 90 min of LPS injection, the bioactivity of plasma tumor necrosis factor-alpha (TNF-alpha) increased to 98.2 +/- 5.1 ng/ml in mice fed fish oil compared with 32.6 +/- 3.6 ng/ml in those fed the reference diet (P < 0.05). Plasma prostaglandin E2 (PGE2) levels after LPS injection of mice fed the control diet increased within 90 min to 16.4 +/- 5.1 pg/ml. Mice fed the fish oil diet did not show any elevation in plasma PGE2 levels at that time (P < 0.05). We speculate that dietary n-3 fatty acids suppressed PGE2-related responses, including a PGE2-dependent negative feedback on TNF-alpha production, which resulted in differential modulation of sickness behavior depending on the locus of inflammation.
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PMID:Dietary n-3 fatty acids differentially affect sickness behavior in mice during local and systemic inflammation. 914 33

The coincidental behavioral and physiological responses to inflammatory stimuli administered either peripherally or centrally were evaluated. In the first study, twenty castrated male pigs were injected ip with 0, 0.5, 5, or 50 microg/kg BW lipopolysaccharide (LPS). Body temperature was monitored telemetrically, and serial blood samples were collected via an indwelling jugular catheter for determination of plasma cortisol and tumor necrosis factor-alpha (TNF-alpha) concentrations. Sickness behaviors were measured during 10-min tests at 0, 2, 4, 8, 12, and 24 h post injection. The 5 and 50 microg/kg doses of LPS increased plasma concentrations of cortisol and TNF-alpha, while inducing anorexia, hypersomnia, and fever. In contrast, although 0.5 microg/kg LPS induced acute anorexia, hypersomnia, and fever, it did not increase plasma TNF-alpha; and the cortisol response was small and transient, suggesting the behavioral system in pigs is more responsive to LPS than the hypothalamic-pituitary-adrenal (HPA) axis. Because LPS-induced behavior and activation of the HPA axis involve proinflammatory cytokines in the brain, in a second study, unrestrained pigs with jugular catheters were injected intracerebroventricularly (I.C.V.) with recombinant porcine TNF-alpha. Vehicle or TNF-alpha (0, 5, or 50 ng/kg) was injected I.C.V., and plasma cortisol and behavior were determined as before. Pigs injected I.C.V. with 50 ng/kg TNF-alpha showed anorexia, hypersomnia, and an abrupt increase in plasma cortisol concentration. Whereas 5 ng/kg TNF-alpha I.C.V. also induced marked sickness behavior, it failed to stimulate the HPA axis, as indicated by plasma cortisol levels. That there was a distinct difference in the magnitude of behavioral and endocrine responses to LPS and TNF-alpha suggests that different systems that are responsive to inflammatory stimuli exhibit different sensitivities.
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PMID:Coincidental changes in behavior and plasma cortisol in unrestrained pigs after intracerebroventricular injection of tumor necrosis factor-alpha. 916 24

Administration of endotoxin (lipopolysaccharide, LPS) induces profound anorexia. Injection of leptin decreases food intake in mice. Recently, we reported that LPS and cytokines increase leptin levels in hamsters. To further investigate the role of leptin in the LPS-induced anorexia, we administered LPS to leptin receptor-deficient (db/db) and leptin-deficient (ob/ob) mice. We found that LPS caused anorexia in both db/db and ob/ob mice. As might be predicted if leptin had a role in anorexia, the db/db mice were somewhat resistant to LPS-induced anorexia. However the ob/ob mice were more sensitive to LPS-induced anorexia. No differences between db/db and ob/ob mice and their respective littermate were observed in circulating tumor necrosis factor levels after LPS. These data suggest that leptin per se is not essential for LPS-induced anorexia.
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PMID:LPS-induced anorexia in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice. 924 48

Behavioral symptoms of sickness that develop in response to lipopolysaccharide (LPS) and proinflammatory cytokines include depressed locomotion, anorexia, and reduced social activities. The way maternal behavior is affected in response to cytokines has, however, not yet been investigated. We checked that lactating mice are sensitive to LPS by showing that LPS- (400 microg/kg, ip) injected mice ate and drank less than saline-injected mothers and displayed a decreased rectal temperature. At an ambient temperature of 22 degrees C, nest building was significantly decreased in LPS-treated mothers compared to saline-treated animals, whereas pup retrieving, while slower, was still present and globally as efficient as for saline-treated mice. In a second experiment, dams were either injected with physiological saline or LPS but were also exposed to a cold ambient temperature (6 degrees C) or kept in standard external condition (22 degrees C). LPS-treated mice exposed to cold expressed not only pup-retrieving but also nest-building activity. These differential results indicate that the behavioral expression of LPS-induced sickness depends on the priority of the behavior under consideration.
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PMID:Differential effects of lipopolysaccharide on pup retrieving and nest building in lactating mice. 929 60

Anorexia and weight loss are major problems in the care of cancer patients. Data from laboratory studies using an animal model of tumor-induced anorexia suggest that energy intake may be regulated in the tumor-bearing host as it is in healthy animals. The purpose of the present study was to determine if hypophagic tumor-bearing rats would alter their food intake in response to manipulations known to affect food intake in normal healthy animals. Both tumor-bearing and healthy animals increased their food intake when housed at 22 versus 25 degrees C and reduced their food intake when injected with anorexigenic doses of bacterial lipopolysaccharide or interleukin-1 alpha. These data suggest that selected physiological responses affecting short-term food intake are intact in the hypophagic tumor bearing host.
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PMID:Short-term regulation of energy intake is intact in hypophagic tumor-bearing rats. 933 96

The effects of indomethacin, a cyclooxygenase inhibitor, upon plasma concentrations of prostaglandin E2 (PGE2), the febrile response, and metabolic and hematological alterations induced by lipopolysaccharide (LPS) were studied. Experimental endotoxemia was provoked via i.p. injection of 1.0 mg E coli LPS/kg in rats (group A). Indomethacin was introduced/os (2.5 mg/kg) 30 min prior to LPS challenge (group B). Pretreatment with this medication completely inhibited the hyperthermic response to LPS and eliminated the LPS-induced non-specific symptoms of anorexia, adipsia, reduced locomotory activity and gastrointestinal troubles. Plasma PGE2 concentrations increased as early as the 2nd h after the LPS challenge but were blocked when endotoxin application was preceded by indomethacin treatment. Indomethacin did not significantly influence hematological parameters. The dynamics of hematocrit and erythrocyte counts were similar in both groups with a decrease up to the 2nd h followed by an increase to maximum at post-treatment day 3. Pretreatment with indomethacin did not influence the endotoxin-induced leukopenia observed at the 2nd h or the accompanying neutropenia and left shift. Cyclooxygenase inhibition affected total protein concentrations; they were decreased in the early hours of the study (hours 4-6) in both groups. The later tendency towards increase in total protein concentrations was more expressed in animals from group B. Changes in blood glucose were characterized by a permanent tendency towards decrease after hour 2 of LPS challenge up to day 6 (group A). In group B, a similar tendency was observed, but glucose concentrations decreased between hours 2-6 and then returned to initial values.
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PMID:Effects of indomethacin on lipopolysaccharide-induced plasma PGE2 concentrations and clinical pathological disorders in experimental endotoxemia. 946 1

Bacterial lipopolysaccharide (LPS) or endotoxin induces neurological manifestations including anorexia. It is proposed that LPS-induced cytokine production is involved in the generation of neurological manifestations and in neuroinflammatory/immunological responses during gram-negative infections. For example, LPS-induced effects can be blocked or ameliorated by the interleukin-1 receptor antagonist (IL-1Ra). Here, sensitive and specific RNase protection assays were used to investigate the effects of the intracerebroventricular (i.c.v.) administration of LPS on mRNA levels of interleukin-1beta (IL-1beta) system components, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, and neuropeptide Y (NPY) in the cerebellum, hippocampus, and hypothalamus. The same brain region sample was analyzed with all of the antisense probes. The data show simultaneous local induction of multiple cytokine components messenger ribonucleic acids (mRNAs) within specific brain regions in anorectic rats responding to i.c.v. administered LPS (500 ng/rat). Interleukin-1beta and IL-1Ra had a similar mRNA induction profile (hypothalamus > cerebellum > hippocampus). Interleukin-1 receptor type I (IL-1RI) mRNA also increased in all three brain regions examined, and the soluble form of IL-1 receptor accessory protein (IL-1R AcP II) mRNA was induced in the hypothalamus. Tumor necrosis factor-alpha mRNA levels increased in the hypothalamus > hippocampus > cerebellum. Levels of membrane bound IL-1R AcP, TGF-beta1, and NPY mRNAs did not change significantly in any brain region. The results suggest that: (1) endogenous up-regulation of IL-1beta and TNF-alpha in the hypothalamus contribute to LPS-induced anorexia; and (2) the ratio IL-1Ra/IL-1beta, and IL-1beta <--> TNF-alpha interactions may have implications for gram-negative infections associated with high levels of LPS in the brain-cerebrospinal fluid.
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PMID:Interleukin-1beta system (ligand, receptor type I, receptor accessory protein and receptor antagonist), TNF-alpha, TGF-beta1 and neuropeptide Y mRNAs in specific brain regions during bacterial LPS-induced anorexia. 957 Jul 21


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