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)

BACKGROUND: Recent findings have established an association between obesity and immune dysfunction. However, most of the studies investigating the effects of obesity on immune function have been carried out in genetically obese rodent models. Since human obesity is mostly due to intake of a high fat diet and decreased energy expenditure, we asked whether immunological defects also occur in diet-induced obesity. Specifically, we focused on the function of monocytes and macrophages, as these cells are thought to be involved in the low-grade inflammation present in obesity. METHODS: Male Sprague-Dawley rats were fed a high-fat or a standard chow diet for either 2 or 10 weeks. At the end of the intervention period animals were anaesthetised, blood collected for determination of plasma mediator concentrations and lipopolysaccharide (LPS) stimulated production of TNF-alpha by monocytes. LPS stimulated production of TNF-alpha in alveolar macrophages was also determined. RESULTS: High-fat feeding for either 2 or 10 weeks resulted in significant increases in fat mass and serum leptin. Although increased serum leptin has previously been linked to modulation of innate immunity, we found no significant difference in the LPS stimulated production of TNF-alpha by either blood monocytes or alveolar macrophages between the dietary groups. Furthermore, we failed to find a significant increase in circulating TNF-alpha concentrations in obese animals, as reported for genetically obese animals. CONCLUSION: Our data suggest that defects in innate immune function observed in genetically obese animals are not mimicked by dietary obesity, and may more likely reflect the gross abnormality in leptin function of these models. Further work is required delineate the effects of dietary obesity on inflammatory state and immune function.
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PMID:Unaltered TNF-alpha production by macrophages and monocytes in diet-induced obesity in the rat. 1581 57

Immune activation, either by cytokines or endotoxin, elicits a constellation of nonspecific symptoms such as weakness, malaise, listlessness, fatigue, adipsia, anorexia, depression and anxiety collectively termed as sickness behavior. Further, endotoxin administration in animals has been implicated in the pathogenesis of many types of liver disease. Green tea, a common household drink, is rich in antioxidant polyphenols demonstrating inhibitory effects on cytokine production. The present study was designed to investigate the effect of chronic treatment of green tea extract (GTE) on lipopolysaccharide (LPS)-induced sickness behavior and liver damage in rats. The hypothesis was tested through the analysis of LPS-induced behavioral changes in rats, in plus maze and open field paradigms. Other parameters such as feeding and water consumption, weight loss and organ weight index were also estimated. Liver function tests were conducted to investigate the effect of GTE supplementation on LPS-induced hepatic dysfunction. The results of the study demonstrated that GTE significantly attenuated LPS-induced sickness behavior as well as hepatic damage either by its antioxidant activity or by inhibiting LPS induced cytokine production in rats.
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PMID:Green tea (Camellia sinensis) extract ameliorates endotoxin induced sickness behavior and liver damage in rats. 1644 65

Infection and inflammation strongly inhibit a variety of behaviors, including exploration, social interaction, and food intake. The mechanisms that underlie sickness behavior remain elusive, but appear to involve fatigue and a state of hypo-arousal. Because histaminergic neurons in the ventral tuberomammillary nucleus of the hypothalamus (VTM) play a crucial role in the mediation of alertness and behavioral arousal, we investigated whether the histaminergic system represents a target for immune activation and, if so, whether modulation by ascending medullary immune-sensitive projections represents a possible mechanism. Rats were injected intraperitoneally with either the pro-inflammatory stimulus lipopolysaccharide (LPS) or saline, and exposed to one of various behavioral tests that would induce motivated behavior (exploration, play behavior, social interaction, sweetened milk consumption). Upon kill, brains were processed for c-Fos and histidine decarboxylase immunoreactivity. LPS treatment reduced behavioral activity and blocked behavioral test-associated c-Fos induction in histaminergic neurons of the VTM. These effects of LPS were prevented by prior inactivation of the caudal medullary dorsal vagal complex (DVC) with a local anesthetic. To determine whether LPS-responsive brainstem projection neurons might provide a link from the DVC to the VTM, the tracer Fluorogold was iontophoresed into the VTM a week prior to experiment. Retrogradely labeled neurons that expressed c-Fos in response to LPS treatment included catecholaminergic neurons within the nucleus of the solitary tract and ventrolateral medulla. These findings support the hypothesis that the histaminergic system represents an important component in the neurocircuitry relevant for sickness behavior that is linked to ascending pathways originating in the lower brainstem.
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PMID:Lipopolysaccharide suppresses activation of the tuberomammillary histaminergic system concomitant with behavior: a novel target of immune-sensory pathways. 1808 68

Twenty-four Angus x Hereford crossbred steers (247 kg BW; SE = 2.4 kg) were used in a completely random design to evaluate the effect of energy source and level with or without antibiotic administration on measures of immune function. Steers were fed 1 of 3 dietary treatments: a 70% concentrate diet ad libitum (70AL), a 30% concentrate diet ad libitum (30AL), and a 70% concentrate diet offered in an amount calculated to provide NE(g) intake equal to the 30AL treatment (70RES). Half the steers in each dietary treatment received a s.c. injection of tilmicosin phosphate (ANTI; 1 mL/30 kg of BW); the other half received an equal volume of saline s.c. (SAL). Steers were offered the treatment diets for 28 d before and were administered the ANTI or SAL injections 2 d before indwelling catheters were placed in the jugular vein and 2.0 microg/kg of BW of Escherichia coli lipopolysaccharide (LPS) was administered i.v. Blood serum was collected at 30-min intervals from -2 to 6 h and at 8, 12, 24, 48, and 72 h relative to the LPS challenge. Increased energy intake (70AL) increased (P < or = 0.04) DMI, ADG, and rectal temperature (RT) after the challenge compared with the 70RES treatment. The 30AL treatment increased the maximum concentrations and area under the response curve of the proinflammatory cytokines (PIC) interferon-gamma, tumor necrosis factor-alpha, and IL-6 (P < or = 0.05) compared with the average of the 70AL and 70RES treatments. Decreased energy intake (70RES vs. 70AL) increased IL-6 (P < or = 0.003) but did not significantly increase interferon-gamma and tumor necrosis factor-alpha (P > or = 0.14) after LPS administration. Tilmicosin administration decreased the time to attain maximal RT (P = 0.01) by 1 h without altering the peak RT (P = 0.85), and tilmicosin interacted with energy intake to increase prechallenge PIC in 70RES vs. 70AL (P < or = 0.05). Results indicate that increased PIC response, presumably resulting from a combination of decreased energy intake and from direct effects of roughage, may be a mode of action for the slight decrease in morbidity that often occurs when newly received, stressed calves are fed roughage-based receiving diets. Tilmicosin phosphate might have immunomodulatory capacity beyond its direct effects on pathogenic bacteria, and these effects could interact with dietary energy intake in cattle.
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PMID:Effects of dietary energy source and level and injection of tilmicosin phosphate on immune function in lipopolysaccharide-challenged beef steers. 1840 86

The anti-inflammatory cytokine interleukin (IL)-10 is important for regulating inflammation in the periphery and brain, but whether it protects against infection- or age-related psychomotor disturbances and fatigue is unknown. Therefore, the present study evaluated motor coordination, time to fatigue, and several central and peripheral proinflammatory cytokines in male young adult (3-mo-old) and middle-aged (12-mo-old) wild-type (IL-10(+/+)) and IL-10-deficient (IL-10(-/-)) mice after intraperitoneal injection of lipopolysaccharide (LPS) or saline. No age-related differences were observed; therefore, data from the two ages were pooled and analyzed to determine effects of genotype and treatment. LPS treatment increased IL-1beta, IL-6, and TNFalpha mRNA in all brain areas examined in IL-10(+/+) and IL-10(-/-) mice, but to a greater extent and for a longer time in IL-10(-/-) mice. Plasma IL-1beta and IL-6 were increased similarly in IL-10(+/+) and IL-10(-/-) mice 4 h after LPS but remained elevated longer in IL-10(-/-) mice, whereas TNFalpha was higher in IL-10(-/-) mice throughout after LPS treatment. Motor performance and motor learning in IL-10(+/+) mice were not affected by LPS treatment; however, both were reduced in IL-10(-/-) mice treated with LPS compared with those treated with saline. Furthermore, although LPS reduced the time to fatigue in IL-10(+/+) and IL-10(-/-) mice, the effects were exacerbated in IL-10(-/-) mice. Thus the increased brain and peripheral inflammation induced by LPS in IL-10(-/-) mice was associated with increased coordination deficits and fatigue. These data suggest that IL-10 may inhibit motor deficits and fatigue associated with peripheral infections via its anti-inflammatory effects.
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PMID:Exacerbated fatigue and motor deficits in interleukin-10-deficient mice after peripheral immune stimulation. 1865 Mar 18

Work-related respiratory symptoms, including dyspnoea, cough, fever, tiredness and malaise, were recorded in two customs officers employed in 2 depositories of confiscated cigarettes, of which one showed signs of dampness. Microbiological sampling of the air and the cigarettes stored in a damp depository revealed the presence of potentially pathogenic fungi and bacteria and the biochemical markers of bacterial lipopolysaccharide and fungal biomass. The Penicillium species (P. simplicissimum, P. inflatum, P. commune) dominated in the damp depository, while in the other one Aspergillus fumigatus was prevalent. The patients under study did not show a specific sensitization to microbial allergens in the precipitin test, the test for inhibition of leukocyte migration and the bronchial provocation challenge, except for a weak reaction to fungal allergens in the test for inhibition of leukocyte migration. Moreover, one patient responded with subjective symptoms after exposure to inhalation of increased doses of Penicillium simplicissimum antigen. Both cases were diagnosed as a specific form of organic dust toxic syndrome (ODTS). It is hypothesized that the symptoms were evoked most probably by the non-specific action of low molecular fungal metabolites, such as mycotoxins or VOCs (volatile organic compounds), with the possible contribution of bacterial endotoxin. However, as there is no a direct proof to support this presumption, and the effects of nicotine and other tobacco constituents cannot be excluded, further studies are needed to elucidate etiopathogenesis of the disorders associated with the exposure to stored tobacco.
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PMID:Respiratory disorders in two workers of customs depositories occupationally exposed to mouldy tobacco. 1906 Dec 69

Although fever and sickness behavior are common responses to infection, it has been proposed that the sickness behaviors associated with infection, in particular lethargy and fatigue, may be more valuable clinical markers of illness and recovery in patients, than is body temperature alone. Measuring abdominal temperature, food intake and wheel running we therefore determined the dose thresholds and sensitivities of these responses to lipopolysaccharide (LPS). Male Sprague-Dawley rats were randomly assigned to receive one of three LPS doses (10, 50, 250 microg/kg), or saline, subcutaneously. Administration of LPS induced a dose-dependent increase in abdominal temperature and decrease in wheel running, food intake and body mass. Regression analysis revealed that decreased running was the most-sensitive of the sickness responses to LPS administration, with a regression slope of -41%/log microg, compared to the slopes for food intake (-30%/log microg, F(1,2)=244, P=0.004) and body mass (-2.2%/log microg, F(1,5)=7491, P<0.0001). To determine the likelihood that exercise training influenced the sickness responses we measured in our dose-response study we performed a second experiment in which we investigated whether fever and anorexia induced by LPS administration would present differently depending on whether rats had been exercising or sedentary. Six weeks of wheel running had no effect on the magnitude of fever and anorexia induced by LPS administration. Avoidance of physical activity therefore appears to be a more-sensitive indicator of a host's reaction to LPS than is anorexia and fever.
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PMID:Avoidance of physical activity is a sensitive indicator of illness. 1906 7

Chronic fatigue syndrome, infection and oxidative stress are interrelated in epidemiological case studies. However, data demonstrating scientific validation of epidemiological claims regarding effectiveness of nutritional supplements for chronic fatigue syndrome are lacking. This study is designed to evaluate the effect of natural polyphenol, curcumin, in a mouse model of immunologically induced fatigue, where purified lipopolysaccharide (LPS) and Brucella abortus (BA) antigens were used as immunogens. The assessment of chronic fatigue syndrome was based on chronic water-immersion stress test for 10 min daily for 19 days and the immobility time was taken as the marker of fatigue. Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time and hyperalgesia on day 19, as well as marked increase in serum tumor necrosis factor-alpha (TNF-alpha) levels. Concurrent treatment with curcumin resulted in significantly decreased immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as TNF-alpha levels. These findings strongly suggest that during immunological activation, there is significant increase in oxidative stress and curcumin can be a valuable option in the treatment of chronic fatigue syndrome.
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PMID:Curcumin, a polyphenolic antioxidant, attenuates chronic fatigue syndrome in murine water immersion stress model. 1915 25

It is believed that physical stress, infection and oxidative stress are involved in the development of chronic fatigue syndrome. There is little evidence stating the beneficial role of nutritional supplements in chronic fatigue syndrome. Based on this, this study was designed to evaluate the effect of naringin, a natural polyphenol, in a mouse model of immunologically-induced fatigue, wherein purified lipopolysaccharide (LPS) as well as Brucella abortus (BA) antigen was used as immunogens. The assessment of chronic fatigue syndrome was based on chronic water-immersion stress test for 10 mins as well as measurement of hyperalgesia for 19 days. Immobility time and tail withdrawal latency as well as oxidative stress were taken as the markers of fatigue. Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time, hyperalgesia and oxidative stress on 19th day. Serum tumor necrosis factor-alpha (TNF-alpha) levels markedly increased with LPS or BA challenge. Concurrent treatment with naringin resulted in the significant decrease in the immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as in TNF-alpha levels. Present findings strongly suggest the role of oxidative stress and immunological activation in the pathophysiology of chronic fatigue syndrome, and treatment with naringin can be a valuable option in chronic fatigue syndrome.
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PMID:Modulation of antigen-induced chronic fatigue in mouse model of water immersion stress by naringin, a polyphenolic antioxidant. 1946 4

Three decades after the coining of the term chronic fatigue syndrome, the diagnosis of this illness is still symptom based and the aetiology remains elusive. Chronic fatigue syndrome pathogenesis seems to be multifactorial and the possible involvement of immune system is supported. The present study was designed to evaluate the effects of the epigallocatechin gallate in a mouse model of immunologically induced chronic fatigue. On 19th day, after lipopolysaccharide/Brucella abortus administration, the mice showed significant increase in immobility period, post swim fatigue and thermal hyperalgesia. Behavioral deficits were coupled with enhanced oxidative-nitrosative stress as evident by increased lipid peroxidation, nitrite levels and decreased endogenous antioxidant enzymes (superoxide dismutase, reduced glutathione and catalase) and inflammation (increased levels of tumor necrosis factor-alpha and tissue growth factor-beta). Chronic treatment with epigallocatechin gallate restored these behavioral and biochemical alterations in mice. The present study points out towards the beneficial effect of epigallocatechin gallate in the amelioration of chronic fatigue syndrome and thus may provide a new, effective and powerful strategy to treat chronic fatigue syndrome.
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PMID:Epigallocatechin gallate ameliorates chronic fatigue syndrome in mice: behavioral and biochemical evidence. 1964 48


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