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)

The immunostimulant poly(A)-poly(U) induces a rapid enhancement of circulating colony-stimulating activity (CSA) in normal mice, culminating 2 h after i.v. injection. A dose of 200 micrograms per mouse is sufficient for a maximal effect. The colonies formed in response to sera from poly(A)-poly(U)-injected mice are mainly granulocytic with few macrophages. These sera are devoid of detectable interleukin 3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF), but contain large amounts of interleukin 6 (IL-6) that are perfectly correlated with circulating CSA levels. Although, in our hands, IL-6 alone induces no colony formation in the standard methylcellulose colony assay, it is nevertheless requisite for this biological activity because 1) monoclonal antibodies against IL-6 strongly diminish colony formation in response to sera from poly(A)-poly(U)-injected mice, and 2) recombinant (r)IL-6 induces colonies when tested in combination with low amounts of normal murine serum. At the concentrations used (0.3%-2.5%), the latter has no or a very slight effect alone. Low amounts of hematopoietic growth factors, that is, macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF), GM-CSF, or IL-3 that are almost ineffective in the absence of IL-6 can replace normal serum. Taken together, these data suggest that circulating IL-6, induced by i.v. injection of poly(A)-poly(U), promotes colony formation by interacting with serum components that might be identical with hematopoietic growth factors present in normal serum at subliminal concentrations. Finally, the involvement of lipopolysaccharide (LPS) in this phenomenon has been ruled out by the use of the low responder strain of mice (C3H/HeJ) that leads to similar results.
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PMID:Poly(A)-poly(U) induces circulating colony-stimulating activity resulting from interactions between endogeneous interleukin 6 and serum components. 205 90

In unprimed mice, a single injection of a non-lethal dose of lipopolysaccharide (LPS) produced a rise in tumor necrosis factor (TNF) and interleukin 6 (IL 6) activities. Peak serum concentrations were attained, respectively, 1.5 hr and 2.5 hr after the challenge. Pretreatment with recombinant human TNF-alpha (rHuTNF) had a priming effect for enhanced production of both serum cytokines without any change in kinetics. The enhancement was more pronounced in the TNF (15-fold) than in the IL 6 (4-fold) response. Recombinant murine TNF caused a comparable increase in LPS-induced cytokine release. In contrast, comparable pretreatment with another macrophage-derived cytokine, recombinant human interleukin 1 beta (HuIL1-beta), revealed a negative effect on LPS-induced TNF release whereas IL 6 in the blood reached levels similar to those found after priming with rTNF. Moreover, when administered in combination with rHuTNF, rHuIL1-beta inhibited the priming effect on TNF autocrine production.
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PMID:Differential priming for endotoxin-induced circulating cytokine production by tumor necrosis factor-alpha and interleukin 1 beta. 210 35

The purpose of these studies was to test whether pentoxifylline, a drug that can inhibit the production and action of cytokines hypothesized to be endogenous pyrogens (for example, interleukin 1 and tumor necrosis factor [TNF]), is antipyretic. We also tested the effects of pentoxifylline on plasma activities of interleukin 6 (IL 6) and TNF in response to an injection of a fever-inducing dose of lipopolysaccharide (LPS). Our results showed that a high dose of pentoxifylline (200 mg/kg) caused hypothermia in control rats and blocked LPS fever, while a low dose (50 mg/kg) did not have these effects. Injection of the high dose of pentoxifylline in control rats caused a rise in plasma IL 6 but not in plasma TNF. However, the peak levels of plasma IL 6 and TNF activities following an injection of LPS were significantly reduced by pretreatment with pentoxifylline. Overall, the data are consistent with the hypothesis that pentoxifylline is an antipyretic drug, which may act at least in part by inhibiting the secretion of pyrogenic cytokines.
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PMID:The effects of pentoxifylline on lipopolysaccharide (LPS) fever, plasma interleukin 6 (IL 6), and tumor necrosis factor (TNF) in the rat. 210 30

Exposure of Mono-Mac-6 cells to lipopolysaccharide (LPS) can induce rapid and transient expression of cytokines like tumor necrosis factor (TNF), interleukin 1 and interleukin 6. Preculture of Mono-Mac-6 cells in culture medium containing small amounts (1-50 ng/ml) of LPS for 3 days leads to an unresponsiveness to a subsequent stimulation with a high amount of LPS. This in vitro desensitization of a monocytic cell line may serve as a model for desensitization to LPS seen in vivo, for example in mice or man repetitively treated with LPS. Addition of interferon-gamma (IFN-gamma) to the Mono-Mac-6 cells during the LPS preculture period leads to an inhibition of desensitization, whereas addition of IFN-alpha or IFN-beta is not able to inhibit the LPS-induced desensitization. The inhibition of desensitization by IFN-gamma was dose dependent and time dependent. Preculture of Mono-Mac-6 cells with LPS leads to a strong reduction of TNF mRNA. This reduction of specific mRNA is also overcome by addition of IFN-gamma, but not by IFN-alpha and IFN-beta, indicating that pretranslational mechanisms are responsible for the regulation of TNF in desensitization.
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PMID:Inhibition of lipopolysaccharide-induced in vitro desensitization by interferon-gamma. 211 78

Seven patients with advanced epithelial carcinoma and ascites, relapsing after two or more regimens of standard chemotherapy, have been treated with recombinant gamma-interferon (rIFN-gamma) i.p., via a permanent catheter. rIFN-gamma (Immuneron; Biogen; 0.5 mg = 10(7) IU in 2 liters of saline) was administered 3 times a week, on alternate weeks, for a total of nine courses. No major toxicities were observed: mild fever, malaise, and a flu-like syndrome occurred in all patients. The modulation of immunological parameters was studied. Cytotoxic activity of immunocompetent cells against tumor cell lines was measured both in the peritoneal compartment and in peripheral blood mononuclear cells. A significant increase of cytotoxicity of tumor-associated macrophages was observed in 5 of 7 patients and in 4 of 7 patients with tumor-associated peritoneal lymphocytes. Circulating effector cells were only occasionally stimulated. Tumor-associated macrophages isolated from the ascitic fluid and stimulated with lipopolysaccharide produced higher amounts of interleukin 1 in 5 of 6 patients tested, while interleukin 6 production by unstimulated tumor-associated macrophages was augmented in 2 of 2 patients after rIFN-gamma treatment. Freshly isolated ovarian carcinoma cells from the ascitic fluid has a variable, although usually low, expression of HLA-DR antigens. rIFN-gamma treatment caused a marked increase in HLA-DR expression in all patients tested. Expression of HLA class I antigens was negative in 2 of 5 patients and was strongly increased in 1 of the 2 after treatment. The observation that rIFN-gamma administered i.p. activates in situ effector cells and augments major histocompatibility antigen expression in tumor cells, with minimal toxicity, encourages further efforts to investigate its therapeutic potential in ovarian carcinoma.
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PMID:Intraperitoneal recombinant gamma-interferon in patients with recurrent ascitic ovarian carcinoma: modulation of cytotoxicity and cytokine production in tumor-associated effectors and of major histocompatibility antigen expression on tumor cells. 212 37

To better understand the immediate early genetic response of myeloid cells to terminal differentiation and growth inhibitory stimuli, complementary DNA clones of myeloid differentiation primary response (MyD) genes have recently been isolated. In this study, a set of known (junB, c-jun, ICAM-1, H1(0), and H3.3 histone variants) and novel (MyD88, MyD116) MyD genes were used as immediate early molecular markers to further dissect the primary genetic response of myeloid cells to various differentiation and growth inhibitory stimuli. Expression of all of these MyD genes was highly induced in autonomously replicating differentiation inducible M1D+ myeloblasts following induction of terminal differentiation and growth inhibition by interleukin 6. Expression of all MyD genes except MyD88 was induced upon inhibition of M1D+ cell growth and induction of early, but not late, differentiation markers by interleukin 1 and lipopolysaccharide. In sharp contrast, only expression of H1(0) and H3.3 histone variants was increased following inhibition of M1D+ cell growth by interferon beta or gamma, which did not induce any differentiation associated properties. No increase in the expression of any of these MyD genes was seen in a clone of WEHI-3B D- myelomonocytic cells following stimulation with interleukin 6, which neither induced it for differentiation nor inhibited its growth. 12-O-Tetradecanoylphorbol-13-acetate, known to be a potent inducer of jun expression in many cell types, failed to induce high or stable expression of junB and c-jun in M1D+ cells, where it did not induce differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dissection of the immediate early response of myeloid leukemia cells to terminal differentiation and growth inhibitory stimuli. 212 51

Macrophages, unlike CD4+ T cells, can be productively infected by human immunodeficiency virus (HIV) without prior cellular activation. Cytopathic infection ensues without the induction of tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), or tissue factor genes. In detailed studies on TNF alpha, HIV infection did not affect the regulation of TNF alpha in response to bacterial lipopolysaccharide. In an effort to examine the interferon responsiveness of HIV-infected macrophages, the cells were challenged with vesicular stomatitis virus (VSV) with or without interferon pretreatment. Surprisingly, HIV-infected macrophages were completely resistant to VSV-induced lysis even in the absence of interferon; however, no interferon was detected in the supernatants of these infected cells. The resistance of HIV-infected macrophages to superinfection with VSV indicates a previously undescribed effect of HIV upon macrophage cellular metabolism.
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PMID:Characterization of a macrophage-tropic HIV strain that does not alter macrophage cytokine production yet protects macrophages from superinfection by vesicular stomatitis virus. 217 98

The objective of this study was to analyze monokine production by peripheral blood mononuclear cells from patients with alcoholic cirrhosis. The capacity of peripheral blood mononuclear cells and purified monocytes from these patients to produce tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 was investigated. Spontaneous production of tumor necrosis factor alpha, interleukin 6 and interleukin 1 beta was similar in cirrhotic and healthy subjects, but serum levels of interleukin 6 (less than 2 U/ml vs. 9.5 +/- 3 U/ml) and tumor necrosis factor alpha (3.1 +/- 1.2 pg/ml vs. 12.0 +/- 1.2 pg/ml) were significantly higher in cirrhotic patients. However, peripheral blood mononuclear cells or purified monocytes from patients with alcoholic liver cirrhosis, stimulated in vitro with Escherichia coli lipopolysaccharide, displayed a marked increase of tumor necrosis factor alpha, interleukin 1 beta and interleukin 6 secretions compared with healthy controls. A striking feature of this overproduction was its reversibility as assessed by allowing cells to rest in vitro without lipopolysaccharide for 1 to 7 days before stimulation. In such conditions, tumor necrosis factor alpha and interleukin 6 secretions declined to levels present in healthy subjects in whom production remained stable, whereas interleukin 1 beta secretion markedly decreased in both groups to the point where no difference could be seen. This reversible oversecretion of cytokines after lipopolysaccharide stimulation, along with the lack of abnormality of spontaneous cytokine secretion, suggests that monocytes in these patients may have undergone an in vivo activation process analogous to a priming phenomenon. The in vitro activation with lipopolysaccharide may represent the correlate of in vivo endotoxemia observed during acute events such as sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Excessive in vitro bacterial lipopolysaccharide-induced production of monokines in cirrhosis. 218 15

This study was designed to test the tumor necrosis factor (TNF) WEHI 164 clone 13 bioassay and the interleukin 6 (IL-6) B9 bioassay for sensitivity to endogenously produced dog TNF and IL-6 and then to use these assays to examine the associations between these cytokines and lipopolysaccharide (LPS)-induced fever. When dogs were injected with LPS (40, 10, 1, 0.1, and 0.01 microgram/kg), the resulting fever was dose dependent. A plot of plasma cytokine changes over time following LPS injections showed that the plasma TNF-like activity appeared to increase in an all-or-none dose response, whereas the increase in plasma IL-6-like activity appeared to be log dose dependent. Plasma TNF-like and IL-6-like activity were then separately plotted against temperature change (fever). Statistical analysis supported the interpretation that both TNF-like and IL-6-like activity were related to LPS-fever in an all-or-none manner, with IL-6 having a threshold region. We conclude that if these cytokines are circulating mediators of fever, they may induce fever in an all-or-none fashion.
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PMID:Plasma profiles of IL-6 and TNF with fever-inducing doses of lipopolysaccharide in dogs. 219 79

The purpose of these studies was to assess whether interleukin 6 (IL-6) is an endogenous pyrogen, responsible for all or part of the fever caused by lipopolysaccharide (LPS) in rats. We have found that the core temperature (as measured by biotelemetry) rose significantly after intracerebroventricular (icv) injection of recombinant human IL-6. The same doses of IL-6, when administered intravenously or intraperitoneally, had no effect on body temperature. The fever caused by icv administration of IL-6 was completely blocked by indomethacin. After injection of fever-inducing doses of LPS, the plasma and cerebrospinal fluid (CSF) IL-6 activities rose, the former much more than the latter. The correlation between fever and plasma IL-6 activity was r = 0.84 (P less than 0.0025); the correlation between fever and CSF IL-6 activity was r = 0.77 (P less than 0.015). The results of this study are consistent with the hypothesis that IL-6 is a mediator of LPS-induced fever in the rat.
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PMID:Role of interleukin 6 in fever in rats. 231 25


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