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)

To determine the effect of epinephrine and hydrocortisone on lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) production, human whole blood was stimulated with LPS in the presence or absence of these stress hormones. Epinephrine caused a dose-dependent increase in LPS-induced IL-8 production, which was mediated exclusively via beta-adrenergic receptors, as reflected by the facts that beta (but not alpha) receptor blockade reversed the epinephrine effect and beta (but not alpha) receptor stimulation reproduced the epinephrine effect. Further, elevating cellular cyclic AMP (cAMP) concentrations, a known effect of beta-adrenergic stimulation, by addition of dibutyryl cAMP also enhanced LPS-induced IL-8 production. Epinephrine-induced upregulation of IL-10 production masked an even more pronounced stimulating effect of this hormone on IL-8 synthesis, as indicated by the finding that the extent of IL-8 upregulation was greater in the presence of anti-IL-10 than in the absence of anti-IL-10. Hydrocortisone dose-dependently inhibited LPS-induced IL-8 production and reversed epinephrine-induced enhancement of IL-8 production. Epinephrine and hydrocortisone have opposite effects on IL-8 production, which may be relevant for the understanding of endogenous and therapeutic stress hormone influences on IL-8 mediated inflammation.
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PMID:Lipopolysaccharide-induced interleukin 8 production by human whole blood is enhanced by epinephrine and inhibited by hydrocortisone. 916 77

The purpose of the present study was to characterize the acute changes in the insulin-like growth factor (IGF) system in humans after administration of endotoxin (lipopolysaccharide; LPS). Escherichia coli LPS (4 ng/kg) was injected intravenously into healthy adults, and serial blood samples were collected for the next 5 h; subjects injected with saline served as time-matched controls. LPS administration resulted in a gradual decrease in the total extractable IGF-I concentration, which was reduced by approximately 20% over the final 2 h of the experiment; levels of free IGF-I were not significantly altered. LPS also produced a marked but transient elevation in growth hormone (GH) concentration. IGF-binding protein (BP)-1 levels were elevated more than fivefold 2 h after LPS injection, and thereafter levels gradually returned toward baseline. IGFBP-2 concentration also increased after LPS injection, but the maximal increase (approximately 50% above basal) was observed during the final 2 h of the protocol. In contrast, IGFBP-3 levels did not vary over the period examined in response to LPS, and there was no apparent increase in number of BP-3 proteolytic fragments. Cortisol levels were increased early and remained two- to threefold above baseline throughout the protocol. No significant alterations in serum concentration of glucose or insulin were noted. LPS also produced an early elevation in tumor necrosis factor and a later increase in interleukin-6. These data indicate that the acute changes in the GH-IGF axis in humans in response to LPS are comparable with those observed in humans in other traumatic conditions and in animal models of endotoxemia and infection.
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PMID:Acute alterations in growth hormone-insulin-like growth factor axis in humans injected with endotoxin. 924 74

The emerging view is that reduced feed intake, lean muscle accretion, and growth in immunologically challenged pigs is the result of increased cytokine activity, but this has not been directly tested. To begin addressing this issue, 72 crossbred barrows and gilts (11.55 +/- .19 kg BW) were not fed for 12 h and then injected i.p. with 0, .5, or 5 micrograms/kg of Escherichia coli lipopolysaccharide (LPS). Blood was collected by jugular puncture at 0, 2, 4, 8, 12, and 24 h after injection. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), cortisol, plasma urea nitrogen (PUN), NEFA, and triglycerides were determined. Immunological stress was induced by LPS as indicated by increased secretion of TNF-alpha, IL-6, and cortisol. In pigs receiving 5 micrograms/kg of LPS, plasma TNF-alpha was increased 10-fold at 2 h after injection and was still elevated (P < .01) at 4 h. In these same pigs, plasma concentration of IL-6 was increased at 2 h and peaked at 4 h with levels exceeding baseline values by 200-fold (P < .01). Cortisol was elevated at 2, 4, and 8 h after injection (P < .01). The increased secretion of cytokines and cortisol in pigs injected with 5 micrograms/kg of LPS was followed by an increase in protein degradation, as evidenced by PUN values that were increased two- and threefold at 8 and 12 h after injection, respectively. However, unlike previous reports in laboratory animal species, plasma glucose, NEFA, and triglycerides were not altered by LPS. Nonetheless, as the period of feed deprivation progressed from 12 to 36 h, plasma NEFA and triglycerides increased (P < .05) and plasma glucose tended to decrease. We believe that immunological challenge induces cytokine synthesis and secretion in swine which, in turn, may induce protein catabolism.
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PMID:Time course of increased plasma cytokines, cortisol, and urea nitrogen in pigs following intraperitoneal injection of lipopolysaccharide. 925 May 11

The notion that stress activates central and peripheral pathways to inhibit the menstrual cycle is well accepted, but the initial processes through which this occurs have not been investigated. This study uses a relevant nonhuman primate model to document the cyclic endocrine effects imposed by a moderate short-term stress episode in the follicular phase. The stress paradigm is a 5-day inflammatory/immune-like challenge produced by the administration of bacterial endotoxin [lipopolysaccharide (LPS)], which, through the release of endogenous cytokines and other mediators, induces a physiopathological response similar to a bacterial infection. LPS was administered iv twice daily for 5 days starting on days 2-8 of the follicular phase. The stress challenge resulted in a significant lengthening of the follicular phase in all monkeys. Two distinct groups were observed. In group 1 (n = 5), the mean (+/- SE) length of the follicular phase in the LPS-treated cycle was significantly increased, from 10.2 +/- 0.2 in control cycle 2 to 30.8 +/- 4.3 days (except in one monkey that had a 4-month amenorrheic interval). In group 2 (n = 5), the length of the follicular phase significantly increased but not to exceed the duration of the LPS treatment (9.7 +/- 1.1 vs. 13.6 +/- 1.2). Estradiol concentrations decreased significantly after LPS in group 1 (34.8 +/- 5.5 vs. 16.2 +/- 6.5 pg/mL) and remained suppressed after the challenge. In group 2, estradiol levels remained stationary throughout the 5-day LPS treatment (26.0 +/- 6.5 vs. 25.6 +/- 3.9). Compared with control values at a similar stage of the follicular phase, most LH and FSH values during LPS treatment were higher than controls. Estradiol and gonadotropin surges were delayed by LPS treatment for a varying length of time according to each grp. Significant differences in integrated luteal progesterone concentrations characterized control cycles of groups 1 and 2 (group 1: 36.5 +/- 1.5, group 2: 47.5 +/- 2.6). In group 1, there were no further effects of LPS on luteal progesterone during the treatment and two post-LPS cycles. In contrast, in group 2, integrated luteal progesterone concentrations were significantly decreased in post-LPS cycle 1 (to 36.0 +/- 4.4). Cortisol significantly increased at hour 3 after each morning LPS injection but the amplitude of the response decreased over the 5-day period. Progesterone increased significantly by hour 3 after the first LPS injection but remained unchanged after subsequent LPS administration. Our data demonstrate that a 5-day inflammatory-like episode during the follicular phase can delay folliculogenesis and that damage to this process is intensified in individuals who already demonstrate a subtle cyclic degradation, in the form of decreased progesterone secretion in the luteal phases preceding the stress episode. Long-term endocrine effects, in the form of decreased luteal secretory activity in the first poststress cycle, are observed in normally cycling individuals, suggesting that inadequacy of the luteal phase may represent the first stage in the damage that a stress episode can inflict upon the normal menstrual cycle.
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PMID:Stress and the menstrual cycle: relevance of cycle quality in the short- and long-term response to a 5-day endotoxin challenge during the follicular phase in the rhesus monkey. 966 28

Immunomodulatory activities of constituents isolated from Hydrangeae Dulcis Folium and their related compounds on lymphocyte proliferation were investigated using splenocytes and lymph node cells. Thunberginol A (TA) significantly suppressed B lymphocyte proliferation stimulated by lipopolysaccharide (LPS) at 10(-5) M. However TA at a lower concentration (10(-6) M) and the other compounds, except hydrangenol and 3'-hydroxyhydrangeaic acid, tended to potentiate B lymphocytes proliferation (10(-5) M). On the other hand, thunberginol A significantly suppressed T lymphocyte proliferation stimulated by concanavalin A (Con A), but did not suppress phytohemagglutinin (PHA). Hydrocortisone and cyclosporin A strongly suppressed T lymphocyte proliferation induced by both Con A and PHA. These results suggest that thunberginol A acts on both B and T lymphocytes and may have a suppressive mechanism different from the known immunosuppressants. The cytotoxicity of TA for splenocytes seemed weaker than known immunosuppressants resulting from viability tests using MTT assay and the measurement of lactate dehydrogenase (LDH) released in the medium. Moreover, TA suppressed antigen-specific T lymphocyte proliferation in mice lymph node cells immunized with keyhole limpet hemocyanin (KLH). Thus, these findings show that TA has a suppressive effect on lymphocyte activation, and this inhibitory effect of TA seems to contribute to its suppressive effect on type IV allergies.
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PMID:Development of bioactive functions in Hydrangeae Dulcis Folium. VII. Immunomodulatory activities of thunberginol A and related compounds on lymphocyte proliferation. 974 47

Increased psychologic and physiologic stressors can have profound effects on the immune system. Previously believed to be immunosuppressive, there is mounting evidence that stress may actually induce a shift in the type 1/type 2 cytokine balance toward a type 2 cytokine response. Cortisol is elevated in response to stress and has been reported to alter cytokine production in murine and human peripheral blood mononuclear cells (PBMC). The current investigation examined the effects of dexamethasone (DEX) mimicking basal, stress, and supraphysiologic levels of cortisol on production of interferon-gamma (IFN-gamma) (type-1), interleukin (IL)-12p40 (type 1), IL-10 (type 2), and IL-4 (type 2) by human PBMC. Both supraphysiologic and stress levels of DEX decreased production of type 1 cytokines and either increased or maintained production of type 2 cytokines PBMC stimulated with phytohemagglutinin (PHA), immobilized anti-CD3, lipopolysaccharide (LPS) or tetanus. Although preincubation with DEX was sufficient to induce a type 2 switch in short-term mitogen cultures, PBMC cultures for extended periods of time required DEX at the initiation and throughout the duration of culture. Mifepristone, a glucocorticoid receptor antagonist, blocked the DEX-induced shift in the type 1/type 2 cytokine balance. These data demonstrated the ability of the glucocorticoid dexamethasone, to induce a shift in the type 1/type 2 cytokine balance toward a type 2 cytokine response and simulate the type 1/type 2 cytokine alterations observed in in vivo stress models. This model will allow detailed investigation of the cellular and molecular mechanisms of stress-induced immune alterations in humans.
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PMID:Glucocorticoid-induced type 1/type 2 cytokine alterations in humans: a model for stress-related immune dysfunction. 987 50

Interleukin-1 (IL-1) is a primary mediator of inflammation that is regulated, in part, by the hypothalamic-pituitary-adrenal axis. The purpose of this study was to determine if gender- or age-related differences exist in the sensitivity of IL-1-producing cells to hydrocortisone. Peripheral blood mononuclear cells (PBMC) isolated from men and women (21-77 yr old) were incubated with hydrocortisone (0, 50, 100, 500, or 1,000 ng/ml) with or without lipopolysaccharide (LPS). Secretion of IL-1beta and IL-1 receptor antagonist was inhibited in a dose-dependent manner (P = 0.001) without age- or gender-related differences. Hydrocortisone decreased soluble IL-1 receptor type II (sIL-1RII) secretion by unstimulated cells (P = 0. 0001), but it increased secretion by LPS-stimulated cells (P = 0. 0001) in all groups. Unstimulated cell supernatants from men contained greater concentrations of sIL-1RII than the supernatants from women (P = 0.011). Compared with men, PBMCs from women were less responsive to hydrocortisone inhibition of sIL-1RII secretion, regardless of age (P = 0.001), and compared with the follicular phase, sIL-1RII secretion was lower in the luteal phase of the menstrual cycle (P < 0.05). These data indicate that basal secretion and glucocorticoid modulation of sIL-1RII secretion by cultured PBMCs are gender dependent. Moreover, glucocorticoid influences on sIL-1RII secretion depend on the presence or absence of gram-negative bacterial toxins.
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PMID:Glucocorticoid sensitivity of interleukin-1 agonist and antagonist secretion: the effects of age and gender. 1074 72

The objective of this research was to provide an integrated look at systemic adrenal, somatotropic, and immune responses of growing pigs to challenge with lipopolysaccharide (LPS). Weaned pigs were challenged intraperitoneally with 100 microg/kg BW of LPS or sterile saline, and rectal temperature and blood data were collected for 72 h. Daily feed intake also was monitored. Plasma was analyzed for concentrations of cortisol, tumor necrosis factor alpha (TNFalpha), the acute phase protein haptoglobin, growth hormone (GH), insulin-like growth factor I (IGF-I), and prostaglandin E2 (PGE2). As expected, LPS decreased feed intake, stimulated a febrile response, and activated the hypothalamic-pituitary-adrenal (HPA) axis as demonstrated by increased cortisol levels. Cortisol reached maximum elevation 2 h after treatment (P < .001) and remained elevated through 12 h (P < .001). Circulating TNFalpha was increased by LPS at 2 and 4 h after treatment (P < .001), and an apparent (not statistically significant) increase in haptoglobin also occurred in challenged animals. The LPS injection suppressed IGF-I by 2 h following treatment (P < .01), and circulating IGF-I remained reduced relative to controls through 44 h. Overall, GH was increased in LPS-treated pigs (P < .05), although the treatment x time interaction was not significant. Plasma PGE2 was increased transiently at 2 h (P < .05) and then subsequently suppressed at 4, 8, and 12 h following LPS (P < .05). This study provides a comprehensive view of systemic effects of LPS on components of the HPA, growth, and immune axes. In addition, these are the first data to document changes in circulating PGE2 in unrestrained animals during the early hours of the acute phase response to LPS.
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PMID:Integrated adrenal, somatotropic, and immune responses of growing pigs to treatment with lipopolysaccharide. 1090 32

Cortisol is a steroid hormone produced in response to stress. This glucocorticoid can be toxic to neurons, and thus may be important in neurodegenerative diseases including Alzheimer's disease. Activated microglia produce molecules including nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) which can also be toxic to neurons. The current study was designed to determine the effect of cortisol upon the activation of primary cultured microglia and transformed N9 microglial cells. The studies indicate that cortisol represses lipopolysaccharide (LPS) induction of nitric oxide production in these microglial cells. The hormone acts by inhibiting the production of inducible nitric oxide synthase (iNOS) which catalyses the synthesis of NO. Cortisol likely acts by blocking transcription of iNOS gene expression since the hormone represses LPS induction of iNOS RNA levels in these cells. Activated microglia produce increased TNF-alpha, in addition to increased NO. The current studies demonstrate that cortisol inhibits release of TNF-alpha from LPS-treated microglial cells. Collectively, these data suggest that although cortisol may be directly toxic to neurons, the hormone may indirectly protect neurons by blocking the production of cytotoxic molecules by microglia.
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PMID:Inhibition of microglial cell activation by cortisol. 1092 18

The intron-exon organisation of the carp IL-1beta gene consists of 2455bp and comprises seven exons. Three IL-1beta RNA transcripts have been found in carp: (1) a fully spliced product; (2) exon 1-7 with introns 5 and 6; and (3) exon 1-7 with intron 5 only. The intron-containing products probably represent partially spliced transcripts. IL-1beta mRNA expression in carp was semi-quantitatively analysed by RT-PCR in multiple organs, including brain and pituitary. Constitutive expression of the IL-1beta mRNA was found in these organs with a predominant expression in the immune organs head kidney and spleen. Furthermore, a scattered distribution of IL-1beta producing cells was shown by in situ hybridisations of head kidney tissue. Administration of phorbol-myristate-acetate (PMA), lipopolysaccharide (LPS) or retinoic acid (RA), to phagocytes isolated from the head kidney, resulted in expression of IL-1beta intron-containing transcripts. Of these, only PMA and LPS were stimulators that induced the fully spliced transcript. A role for the nuclear factor (NF)-kappaB pathway in carp IL-1beta expression was shown with suppression of the LPS-induced IL-1beta expression by NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC). Cortisol was able to inhibit in vitro constitutive expression of IL-1beta transcripts. Addition of cortisol simultaneously with LPS could not substantially inhibit transcription.
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PMID:Regulation of interleukin 1 beta RNA expression in the common carp, Cyprinus carpio L. 1116 85


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