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)

Secretion of tumor necrosis factor (TNF)/cachectin occurs during gram-negative bacterial sepsis in response to macrophage stimulation by lipopolysaccharide (endotoxin) and may play an early pivotal role in the subsequent host response. We sought to determine whether administration of: (1) murine monoclonal antibody directed against endotoxin, (2) steroids, or (3) antimicrobial agents would abrogate TNF production and whether the protective capacity would correlate with TNF levels in an experimental model of murine gram-negative bacterial sepsis. Mice were pretreated with anti-lipopolysaccharide monoclonal antibody, gentamicin sulfate, hydrocortisone, or saline and were then challenged with a lethal dose of intraperitoneal Salmonella minnesota. Murine serum TNF levels were measured by the L929 fibroblast cytotoxicity assay. Both gentamicin and anti-lipopolysaccharide monoclonal antibody significantly enhanced survival, and TNF activity at 1.5 and 3 hours was significantly suppressed in animals receiving these agents compared with animals that received either steroids or saline. We conclude that agents such as gentamicin, which inhibits bacterial replication, or monoclonal antibodies, which may neutralize lipopolysaccharide, indeed enhance survival, and survival was correlated with a significant reduction in circulating TNF during the early stages of infection.
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PMID:Decreased tumor necrosis factor production during the initial stages of infection correlates with survival during murine gram-negative sepsis. 229 80

The synthesis of tumor necrosis factor (TNF)/cachectin was assessed in primary monocyte-derived macrophage (MDM) cultures after in vitro infection with a macrophage-tropic strain of HIV-1 (HTLV-IIIBa-L/85). Productive and cytopathic infections in MDM cultures were established using a high multiplicity of infection (m.o.i. = 3) under conditions that minimized endotoxin contamination. Culture supernatants were tested for TNF/cachectin activity by L929 cell cytotoxicity assay, and TNF/cachectin mRNA was assessed by a sensitive PCR amplification technique that could detect between 1 and 10 cells fully activated for TNF/cachectin expression. Unstimulated MDM cultures produced no detectable levels of TNF/cachectin activity or mRNA, consistent with previous demonstrations that production of this cytokine by macrophages is an inducible and not a constitutive event. HIV-1 infection failed to induce detectable TNF/cachectin activity or mRNA in these unstimulated cultures. In addition, the responsiveness of macrophages to lipopolysaccharide (LPS) induction of TNF/cachectin production was assessed in dose-response and kinetic experiments. No differences between infected and uninfected cultures were discernable. These results demonstrate that productive and cytopathic infection with a macrophage-tropic strain of HIV-1 does not alter the regulation of TNF/cachectin expression in macrophages.
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PMID:Human immunodeficiency virus-1 infection of macrophages in vitro neither induces tumor necrosis factor (TNF)/cachectin gene expression nor alters TNF/cachectin induction by lipopolysaccharide. 229 23

The role of tumor necrosis factor (TNF, cachectin), a putative endogenous pyrogen, was investigated by comparing fever and plasma TNF levels after the intraperitoneal and intramuscular injection of 10 micrograms/kg lipopolysaccharide (LPS) into male Sprague-Dawley rats and by neutralization of endogenous TNF using TNF antiserum. An intraperitoneal injection of LPS caused a biphasic fever that lasted approximately 6.5 h. TNF levels in these rats peaked at 657 +/- 222 U/ml at 1 h then declined to virtually undetectable levels by the fourth hour. The intramuscularly injected animals showed a lower monophasic fever and low sustained TNF levels (40 +/- 10 U/ml at 1 h, 18 +/- 11 U/ml at 4 h). In a second study, an antiserum that had been shown to neutralize rat TNF was injected intraperitoneally 2 h before the intramuscular injection of 10 micrograms/kg LPS. Control rats were injected with normal rabbit serum before LPS. During the second hour after the injection of LPS, the animals that received the antiserum developed fevers that tended to be lower than those seen in the rats that were injected with control serum (0.33 +/- 0.06 vs. 0.58 +/- 0.1), although this difference was not significant. However, during the third through eighth hours after LPS, the antiserum-injected rats had mean body temperatures that were significantly higher than those of the control rats (1.62 +/- 0.11 vs. 1.07 +/- 0.09; P = 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antiserum against tumor necrosis factor enhances lipopolysaccharide fever in rats. 230 25

Psychological stress (e.g., exposure to a novel environment) causes a rapid rise in body temperature in rats. In this study, we examined the roles of physical activity and the immune cytokine tumor necrosis factor or cachectin (TNF) in this temperature change. The elevation in temperature of rats exposed to cage-switch stress during the day correlated poorly with the increase in activity (r = 0.07; P = 0.84) and, during cage switch at night, correlated negatively (r = 0.64; P = 0.04). TNF was not detected in the plasma or cerebrospinal fluid of rats after exposure to open-field stress. However, the injection of antiserum against TNF 3.5 h before exposure to the stress of being in an open field resulted in a significantly greater hyperthermia than was seen in the control serum-injected rats (1.38 +/- 0.11 vs. 0.79 +/- 0.14 degrees C; P = 0.002). The peak temperature change after cage-switch stress was similarly increased in rats that had been injected with anti-TNF (0.82 +/- 0.08 vs. 0.50 +/- 0.08 degrees C; P = 0.016). This enhanced hyperthermia is similar to the excessively high fever that occurs during the later phase of lipopolysaccharide fever in animals that have been injected with antiserum against TNF. These data support the hypotheses that stress hyperthermia is a true fever and that TNF is an endogenous antipyretic, limiting the magnitude of this fever.
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PMID:Antiserum against tumor necrosis factor increases stress hyperthermia in rats. 231 7

These experiments provide an explanation for the observation that two intravenous injections of lipopolysaccharide (LPS) spaced 5 h apart in rabbits cause tumor necrosis factor/cachectin (TNF) levels to rise in the blood only after the first LPS injection. Herein we show that treatment of elicited peritoneal exudate rabbit macrophages (PEM) with two doses of LPS given 9 h apart results in a marked reduction in TNF production by the second LPS exposure. This state of hyporesponsiveness is a result of adaptation to LPS, is induced by LPS concentrations that are 1,000-fold less than required to induce TNF production (picograms vs. nanograms), is characterized by a decrease in LPS-induced TNF mRNA without any change in TNF mRNA half-life, is not changed by including indomethacin in cultures, and is specific for LPS since LPS-adapted cells display a TNF response to heat-killed Staphylococcus aureus that is at least as good as that observed in control PEM.
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PMID:Adaptation to bacterial lipopolysaccharide controls lipopolysaccharide-induced tumor necrosis factor production in rabbit macrophages. 231 68

The immunomodulating cytokines, tumour necrosis factor/cachectin (TNF) and lymphotoxin (LT) are thought to play an essential role as mediators of inflammatory reactions. To evaluate the role of TNF and LT in atopic dermatitis (AD) and psoriasis, we investigated their production by mononuclear cells (MNC) in vitro. The 24-h supernatants of lipopolysaccharide (LPS)- and phytohaemagglutinin (PHA)-stimulated and unstimulated MNC from 26 patients with AD and 20 with psoriasis and from 17 non-atopic healthy controls were tested for the concentrations of TNF and LT using an ELISA technique. In patients with AD, TNF levels were significantly decreased in the supernatant of PHA-stimulated (P less than or equal to 0.005) and LPS-stimulated (P less than or equal to 0.02) MNC in comparison to controls. There was no significant difference in TNF production between psoriatic patients and the control group. Release of LT in the supernatant of PHA-stimulated MNC by patients and controls did not differ significantly. There was no significant spontaneous production of TNF and LT by MNC of patients and controls. These studies indicate that different immunomodulating mechanisms are responsible for triggering the inflammatory response in AD and psoriasis.
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PMID:Immunomodulating cytokines in atopic dermatitis and psoriasis: production of tumour necrosis factor and lymphotoxin by mononuclear cells in vitro. 235 11

The bolus injection of tumor necrosis factor (TNF)/cachectin into rats has been reported to induce shock and tissue injury similar to catabolic states seen in cachexia. In the present study, we administered TNF/cachectin to rats by either bolus injection or slow infusion and analyzed the influence on splenocyte mitogen-induced proliferation and interleukin-1 (IL-1) production. Also, TNF administration was compared with lipopolysaccharide (LPS) injection and saline injection. Serum TNF levels were elevated by 30 min following the start of slow infusion, peaked at around 90 min, and remained elevated throughout the 3-h sampling. However, analysis of serum TNF following a bolus injection showed that TNF peaked earlier (30 min) but then declined over the next 2.5 h. LPS infusion resulted in a serum TNF peak at 60-90 min with a rapid decline to near baseline by the end of the 3-h sampling. Spleens were removed from rats following either 3 h of infusion or 3 h following bolus injection, and single-cell suspensions were prepared and analyzed in culture for lymphocyte proliferation to either concanavalin-A (con-A) or pokeweed mitogen (PWM). Adherent spleen cell cultures were also tested for IL-1-forming capacity in response to LPS. The slow infusion of TNF had a suppressive effect on splenic T lymphocyte responsiveness to con-A. This suppressive effect was not observed in the response to the T cell-dependent B cell mitogen PWM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alteration of rat splenocyte blastogenesis and interleukin-1 production following slow infusion of human tumor necrosis factor-alpha. 238 Jul 46

Kupffer cells are the main producers of tumor necrosis factor-alpha (TNF; cachectin) and eicosanoids in the liver exposed to lipopolysaccharide (endotoxin; LPS). A very rapid but transient release of TNF is followed by a slow, steady synthesis of prostaglandin E2 (PGE2). TNF itself is able to provoke eicosanoid synthesis in Kupffer cells; the rate and pattern of prostaglandin production are similar to those observed after treatment with LPS. Anti-TNF antibodies completely neutralize TNF action on Kupffer cells, thus ruling out any participation of contaminating LPS. LPS stimulation of PGE2 production in Kupffer cells is reduced by the antiserum to 50%, indicating an involvement of TNF in the stimulatory action of LPS. On the other hand, PGE2, a potent inhibitor of LPS-elicited TNF release, is able to suppress LPS- but not TNF-stimulated eicosanoid synthesis in rat Kupffer cells. In addition to this autocrine circuit, extrahepatic factors participate in the regulation of Kupffer cell activation: glucocorticoids not only inhibit TNF or prostaglandin production, they also reverse the LPS-specific changes in the prostaglandin pattern of Kupffer cells. LPS, TNF or cycloheximide when given alone in the concentration range applied in this study do not affect the viability of rat Kupffer cells. However, the combinations of cycloheximide and either LPS or TNF cause rapid death of the cultured cells. The cytolytic potential of either combination cannot be alleviated by treatment with glucocorticoids.
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PMID:Interdependence of tumor necrosis factor, prostaglandin E2, and protein synthesis in lipopolysaccharide-exposed rat Kupffer cells. 239 Sep 87

We defined the acute phase behaviour of a number of rabbit plasma proteins in studies (in vivo) and studied the effects of monokine preparations on their synthesis by rabbit primary hepatocyte cultures. Following turpentine injection, increased serum levels of C-reactive protein, serum amyloid A protein, haptoglobin, ceruloplasmin, and decreased concentrations of albumin were observed. In contrast to what is observed in man, concentrations of alpha 2-macroglobulin and transferrin were increased. Co-culture of primary hepatocyte cultures with lipopolysaccharide-activated human peripheral blood monocytes or incubation with conditioned medium prepared from lipopolysaccharide-activated human or rabbit monocytes resulted in dose-dependent induction of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and depression of albumin synthesis, while C-reactive protein synthesis and mRNA levels remained unchanged. A variety of interleukin-1 preparations induced dose-dependent increases in the synthesis and secretion of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and decreased albumin synthesis. Human recombinant tumour necrosis factor (cachectin) induced a dose-dependent increase in synthesis of haptoglobin and ceruloplasmin. In general, human interleukin-1 was more potent than mouse interleukin-1 and tumour necrosis factor. None of the monokines we studied had an effect on C-reactive protein synthesis or mRNA levels. These data confirm that C-reactive protein, serum amyloid A, haptoglobin and ceruloplasmin display acute phase behaviour in the rabbit, and demonstrate that, in contrast to their behaviour in man, alpha 2M and transferrin are positive acute phase proteins in this species. While both interleukin-1 and tumour necrosis factor regulate biosynthesis of a number of these acute phase proteins in rabbit primary hepatocyte cultures, neither of these monokines induced C-reactive protein synthesis. Comparison of these findings with those in human hepatoma cell lines, in which interleukin-1 does not induce serum amyloid A synthesis, suggests that the effect of interleukin-1 on serum amyloid A synthesis may be indirect.
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PMID:Regulation of rabbit acute phase protein biosynthesis by monokines. 246 85

Recombinant interleukin (IL) 1 beta and tumor necrosis factor/cachectin (TNF-alpha) induce, usually within 2 h, a dose-dependent increase in the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF mRNA in cultured human fibroblasts. Maximal induction is reached at about 4-8 h and usually last for at least 48 h. IL 1 beta and TNF have additive effects on the levels of GM- and G-CSF mRNA, and on the secretion of G-CSF activity into the culture medium. IL 1 alpha has the same additive effect that IL 1 beta has with TNF, but no additive effect with IL 1 beta. In contrast, the high basic level of M-CSF (CSF-1) mRNA shows little or lower variations in response to IL 1, TNF-alpha or both IL 1 and TNF-alpha also induce, with similar kinetics, an increase in IL 1 beta but not mRNA level. In contrast to what is observed with macrophages and endothelial cells, E. coli lipopolysaccharide does not modify the fibroblast CSF mRNA level up to 48 h of culture.
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PMID:Interleukin 1 and tumor necrosis factor-alpha additively increase the levels of granulocyte-macrophage and granulocyte colony-stimulating factor (CSF) mRNA in human fibroblasts. 246 2


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