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)

Following infection or injury, sick individuals experience profound psychological and behavioral changes, such as anorexia, depressed activity, and reduced self-care behavior. In the present review, we present evidence for a gender-difference in the behavioral response to sickness. Specifically, following immune activation, sexual activity is suppressed in female, but not in male rats. This gender difference is specific to sexually related responses, because other behaviors, such as locomotion, are equally affected by immune challenges in males and estrous females. The suppression of female sexual behavior, induced by either endotoxin (lipopolysaccharide), or the cytokine interleukin-1 (IL-1), are mediated by central mechanisms that are independent of alterations in ovarian hormone secretion. Furthermore, synergistic effects of the cytokines IL-1 and tumor necrosis factor alpha (TNF alpha) are involved in modulating sexual behavior in sick females, and prostaglandins synthesis is required for the effects of IL-1 on female sexual behavior. The gender difference in the behavioral response to immune activation may be related to the findings that at the same doses and timing in which IL-1 suppressed sexual activity in female but not in male rats, females produced more prostaglandin E2 (PGE2) in the brain, and less corticosterone than males. Finally, we are suggesting that the suppressive effect of cytokines on female reproductive behavior may serve as a mechanism to reduce conception during infection, which exposes the mother and the fetus to dangers such as spontaneous abortions, preterm labor and maternal mortality.
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PMID:The immunobiology of sexual behavior: gender differences in the suppression of sexual activity during illness. 1059 2

Leptin has been implicated in the regulation of anorexia associated with cachexia in rodents and humans. Regulation of leptin expression is under complex endocrine and metabolic control. To determine if leptin expression is regulated by acute inflammation and to define the endocrine and metabolic factor(s) that regulates leptin expression during acute inflammation, castrate male pigs (ad libitum fed, used as their own controls) were treated with saline (control period) and endotoxin (lipopolysaccharide [LPS] period). Frequent blood samples were collected to identify dynamic changes in hormones and metabolites that are known to regulate leptin expression. LPS caused fever and elevated plasma cortisol (p < 0.0004), tumor necrosis factor-alpha (TNF-alpha) (p < 0.0001), and plasma nonesterified fatty acids (NEFA) (p < 0.001) compared with control. Circulating insulin (p < 0.01), glucose (p < 0.003), and insulin-like growth factor-1 (IGF-1) (p < 0.0001), as well as adipose leptin mRNA abundance (p < 0.01), were profoundly reduced following LPS treatment compared with control. Our data indicate that during acute endotoxemia (1-10 h after injection), leptin gene expression is decreased compared with ad libitum fed animals and is more closely related to energy homeostasis than cytokine profiles in plasma.
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PMID:Leptin expression is reduced with acute endotoxemia in the pig: correlation with glucose, insulin, and insulin-like growth factor-1 (IGF-1). 1067 Jun 56

Certain high lean gain swine genotypes have greater sensitivity to pathogen and nonpathogen stressors evident by reduced productivity and increased mortality during disease stress or in suboptimal production environments. Saline (control) and an immunologic challenge (LPS; 25 microg lipopolysaccharide/kg BW) were administered to three genetic populations (each pig used as its own control): high lean (H), moderate lean terminal cross (MT), and moderate lean maternal cross (MM). LPS induced anorexia, and significantly increased body temperature and circulating TNF-alpha, cortisol, and NEFA in all genotypes (P < 0.0004). LPS reduced circulating glucose, insulin, and IGF-1 in all genotypes (P < 0.05). The LPS-induced hypoglycemia was significantly greater in MM versus MT and H pigs (P < 0.03). The hypoinsulinemia was significantly greater in MM versus H pigs (P < 0.02). MM pigs recovered from hypoinsulinemia slower than MT pigs (P < 0.03). Control insulin was higher in H versus MT pigs (P < 0.08), but relative to basal, the insulin response to LPS was similar. Plasma haptoglobin response to LPS was lower for MM versus MT and H pigs (P < 0.02), and tended to be lower in MT versus H pigs (P < 0.09). LPS treatment caused similar decreases in plasma IGF-1 concentrations among genotypes. Ten hours after LPS treatment, leptin mRNA abundance in adipose tissue was significantly reduced (relative to control) in MM and H pigs (P < 0.02) but not in MT pigs (P > 0.05). Physiological differences in leptin, a potent regulator of food intake and energy metabolism, may be important factors in the genetic variation in sensitivity to environmental stress.
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PMID:Physiological response to acute endotoxemia in swine: effect of genotype on energy metabolites and leptin. 1070 65

Poult enteritis and mortality syndrome (PEMS) is an acute, transmissible, infectious intestinal disease associated with high mortality and morbidity in turkey poults. Earlier studies demonstrated immune dysfunction, involving both humoral and cell-mediated immunity, associated with PEMS. The current study examined cytokines and metabolites produced by macrophages from poults exposed to PEMS agent(s). Six trials were conducted with six separate hatches of poults. Poults in the PEMS group were exposed to PEMS agent(s) via contact exposure at 7 days of age whereas uninfected poults served as control poults. Abdominal macrophages were harvested from control (uninfected) and PEMS poults at various times postexposure and cultured for 18-24 hr in the presence of Escherichia coli lipopolysaccharide. Interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) bioactivities and nitrite levels in macrophage culture supernatants were quantified. Macrophage supernatants from PEMS poults had greater IL-1-mediated stimulation index compared with the macrophage supernatants from uninfected control poults in both trials. However, this increase was significant only in trial 1. IL-6 activity tested in three separate trials was significantly higher in PEMS macrophage supernatants over the controls. On the contrary, TNF-alpha production by macrophages was decreased in PEMS macrophage culture supernatants. Nitrite levels in PEMS macrophage culture supernatants were significantly higher in two out of three trials. These findings suggest that the enhanced production of proinflammatory cytokine/metabolites by activated macrophages in PEMS poults may be responsible, at least in part, for the physiological intestinal inflammation, gut motility, and anorexia that characterize this disease.
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PMID:Alterations in macrophage-produced cytokines and nitrite associated with poult enteritis and mortality syndrome. 1073 45

During the course of an infection, profound metabolic and behavioral changes are observed. The resulting decrease in food intake can be reproduced by administration of lipopolysaccharide (LPS) or the proinflammatory cytokines (e.g., interleukin-1 [IL-1] and tumor necrosis factor it induces. To test the possibility that cholecystokinin (CCK) mediates anorexia induced by IL-1 beta and LPS, mice trained to poke their noses in a hole to obtain a food reward according to a fixed ratio (1 reward per 20 actions) were pretreated with the CCK-A receptor antagonist L364,718 (at 1 mg/kg) or with the CCK-B receptor antagonist L365,260 (50 microg/kg) before being injected with LPS (100 microg/kg) or IL-1 beta (20 microg/kg). All injections were given via the intraperitoneal (i.p.) route. In spite of its ability to block the effects of exogenous CCK-8 on food-motivated behavior in mice, the CCK-A receptor antagonist did not block the depressive actions of LPS and IL-1 beta on food-motivated behavior. The CCK-B receptor antagonist was not more effective at blocking. These results do not support a role for CCK in the anorexic effect of LPS and IL-1 beta.
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PMID:Cholecystokinin receptors do not mediate the suppression of food-motivated behavior by lipopolysaccharide and interleukin-1 beta in mice. 1086 99

A single exposure to severe stressors has been shown to cause anorexia in the next 24 h, but the duration of such alterations is not known. Male Sprague-Dawley rats were subjected to different stressors, and food intake was measured for several days after stress. In experiment 1, 2 h of immobilization (Imo) and lipopolysaccharide (LPS) administration (1,000 microgram/kg) caused a marked anorexia in the 24 h after stress, which persisted on poststress day 3. In experiment 2, changes in food intake after LPS and Imo were followed until total recovery. As in experiment 1, LPS caused initially a greater degree of anorexia than Imo, but normal food intake recovered much faster (poststress day 3 vs. poststress day 9). Changing the period of exposure to Imo between 20 min and 6 h (experiment 3) only slightly modified the pattern of response to the stressor. When different doses of LPS (50, 250, and 1,000 microgram/kg) were tested in experiment 4, a dose-dependent effect on food intake was observed, the greatest doses causing the most marked and lasting effect. The present results showed stressor-specific lasting changes in food intake caused by a single exposure to some stressors, the effect of a severe psychological stressor such as Imo being more lasting than that of LPS, despite a lower initial anorexia. A severe psychological stressor and a physical stressor such as LPS appear to change food intake in different ways.
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PMID:Single exposure to stressors causes long-lasting, stress-dependent reduction of food intake in rats. 1095 76

Effects of bilateral subdiaphragmatic vagotomy on food intake and expression of cyclooxygenase-2 mRNA in cerebral vessels in rats intraperitoneally injected with bacterial lipopolysaccharide were studied using in situ hybridization technique. Low doses of lipopolysaccharide decreased food intake in sham-operated animals, but did not affect this parameter in vagotomized rats. Comparison of hybridization signals in brain slices showed that low doses of endotoxin did not affect expression of cyclooxygenase-2 mRNA in vessels of control and experimental animals. High doses of lipopolysaccharide reduced food intake in vagotomized and sham-operated rats and elevated cyclooxygenase-2 mRNA expression in vascular endothelial cells of the brain parenchyma and meninges. The data suggest that the vagus nerve activates central structures responsible for manifestation of anorexia after intraperitoneal injection of low doses of lipopolysaccharide. High doses of endotoxin activate the vagus-independent mechanism of cyclooxygenase-2 synthesis in the endothelium of cerebral vessels. It is assumed that prostaglandins synthesized by cyclooxygenase-2 diffuse into the brain parenchyma and cause anorexia by activating target nerve structures.
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PMID:Effects of vagotomy and bacterial lipopolysaccharide on food intake and expression of cyclooxygenase-2 mRNA in rat brain vessels. 1102 47

Cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) are assumed to mediate anorexia during bacterial infections. To improve our understanding of the role that these two cytokines serve in mediating infection during anorexia, we investigated the ability of pentoxifylline (PTX), a potent inhibitor of TNF-alpha production, to block the anorectic effects of the bacterial products lipopolysaccharide (LPS) and muramyl dipeptide (MDP) in rats. Intraperitoneally injected PTX (100 mg/kg body wt) completely eliminated the anorectic effect of intraperitoneally injected LPS (100 microg/kg body wt) and attenuated the anorectic effect of a higher dose of intraperitoneally injected LPS (250 microg/kg body wt). Concurrently, PTX pretreatment suppressed low-dose LPS-induced TNF-alpha production by more than 95% and IL-1beta production 39%, as measured by ELISA. Similarly, high-dose LPS-induced TNF-alpha production was reduced by approximately 90%. PTX administration also attenuated the tolerance that is normally observed with a second injection of LPS. In addition, PTX pretreatment attenuated the hypophagic effect of intraperitoneally injected MDP (2 mg/kg body wt) but had no effect on the anorectic response to intraperitoneally injected recombinant human TNF-alpha (150 ug/kg body wt). The results suggest that suppression of TNF-alpha production is sufficient to attenuate LPS- and MDP-induced anorexia. This is consistent with the hypothesis that TNF-alpha plays a major role in the anorexia associated with bacterial infection.
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PMID:Inhibition of TNF-alpha production contributes to the attenuation of LPS-induced hypophagia by pentoxifylline. 1108 76

Interleukin-1 (IL-1) mediates symptoms of sickness during the host response to infection. IL-1 exerts its effects via several subtypes of receptors. To assess the role of IL-1 receptor type I (IL-1RI) in the sickness-inducing effects of IL-1, IL-1beta and the cytokine inducer lipopolysaccharide were administered to IL-1RI-deficient mice (IL-1RI-/-). Sickness was assessed by depression of social exploration, anorexia, immobility and body weight loss. IL-1RI-/- mice were resistant to the sickness-inducing effects of IL-1beta administered intraperitoneally (2 microg/mouse) and intracerebroventricularly (2 ng/mouse), but still fully responsive to lipopolysaccharide administered intraperitoneally (2.5 microg/mouse) and intracerebroventricularly (3 ng/mouse). The sensitivity of IL-1RI-/- mice to lipopolysaccharide was not due to a higher brain expression of proinflammatory cytokines other than IL-1, since lipopolysaccharide-induced expression of brain IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 transcripts were identical in IL-1RI-/- and control mice when measured by semiquantitative reverse-transcriptase polymerase chain reaction 1 h after treatment. Blockade of TNF-alpha action in the brain by intracerebroventricular administration of a fragment of the soluble TNF receptor, TNF binding protein (3.6 microg/mouse), attenuated the depressive effects of intraperitoneal injection of lipopolysaccharide (1 microg/mouse) on behaviour in IL-1RI-/- but not in control mice. Since IL-1RI-/- mice were not more sensitive to intracerebroventricularly TNF-alpha (50 ng) than control mice, these results indicate that IL-1RI mediates the sickness effect of IL-1 and that TNF-alpha simply replaces IL-1 when this last cytokine is deficient.
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PMID:Role of interleukin-1beta and tumour necrosis factor-alpha in lipopolysaccharide-induced sickness behaviour: a study with interleukin-1 type I receptor-deficient mice. 1112 55

Individuals affected with either acute or chronic diseases often show disorders of nutrient balance. In some cases, a devastating state of malnutrition known as cachexia arises, brought about by a synergistic combination of a dramatic decrease in appetite and an increase in metabolism of fat and lean body mass. Stimulation of the hypothalamic melanocortin 4 receptor (MC4-R) produces relative anorexia and increased metabolic rate, even in a relatively starved state. Here we demonstrate that cachexia induced by lipopolysaccharide administration and by tumor growth is ameliorated by central MC4-R blockade. MC4-R knock-out mice or mice administered the MC3-R/MC4-R antagonist, agouti-related peptide, resist tumor-induced loss of lean body mass, and maintain normal circadian activity patterns during tumor growth. The final tumor mass is not affected in these animals, providing further support for the potential role of MC4-R antagonism in the treatment of cachexia in disease states.
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PMID:Role of the central melanocortin system in cachexia. 1124 47


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