Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Astrocytes and microglia, both produced interleukin-6 (IL-6) in culture by lipopolysaccharide (LPS) stimulation. IL-6 activity was detected 3-5 h after LPS stimulation and reached a maximum at 10 h. Microglia responded faster than astrocytes. Tumor necrosis factor alpha and interleukin 1 also induced IL-6 mRNA and biological activity in astrocytes, but not in microglia. Among these stimuli, LPS was the most potent inducer of IL-6 production by astrocytes. Our results suggest that different regulatory mechanisms for cytokine production exist in glial cells. The possible roles of astrocytes and microglia in CNS immune responses are also discussed.
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PMID:TNF alpha induces IL-6 production by astrocytes but not by microglia. 150 36

The direct effects of pro-inflammatory cytokines on the contractility of mammalian heart were studied. Tumor necrosis factor alpha, interleukin-6, and interleukin-2 inhibited contractility of isolated hamster papillary muscles in a concentration-dependent, reversible manner. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) blocked these negative inotropic effects. L-Arginine reversed the inhibition by L-NMMA. Removal of the endocardial endothelium did not alter these responses. These findings demonstrate that the direct negative inotropic effect of cytokines is mediated through a myocardial nitric oxide synthase. The regulation of pro-inflammatory cytokines and myocardial nitric oxide synthase may provide new therapeutic strategies for the treatment of cardiac disease.
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PMID:Negative inotropic effects of cytokines on the heart mediated by nitric oxide. 163 60

Tumor necrosis factor alpha (TNF) is thought to play a major role in the pathogenesis of septic shock. Anti-TNF antibody was preadministered in low-dose endotoxin lethality models in which BALB/c mice were challenged with small amounts of lipopolysaccharide following their sensitization with either carrageenan (CAR) or D-galactosamine (D-GalN). Although the antibody virtually eliminated circulating TNF in both the CAR and the D-GalN models, only the D-GalN model mice were afforded survival, adding to a growing body of evidence that substances other than TNF play a key role in endotoxin-induced lethality. Further examination of sera from these mice showed a much greater elevation of interleukin-6 levels in the CAR-sensitized group than in the D-GalN-sensitized group.
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PMID:Experimental elimination of tumor necrosis factor in low-dose endotoxin models has variable effects on survival. 185 80

The regulation of the three major acute-phase proteins alpha 2-macroglobulin, cysteine proteinase inhibitor and alpha 1-antitrypsin by recombinant human interleukin-1 beta, recombinant human interleukin-6 and recombinant human tumor necrosis factor alpha was studied in rat hepatocyte primary cultures. Synthesis and secretion of the acute-phase proteins was measured after labeling with [35S]methionine and immunoprecipitation. Incubation of hepatocytes with interleukin-6 led to dose-dependent and time-dependent changes in the synthesis of the three major acute-phase proteins and albumin, similar to those occurring in vivo during experimental inflammation. alpha 2-Macroglobulin and cysteine proteinase inhibitor synthesis was induced 54-fold and 8-fold, respectively, 24 h after the addition of 100 units/ml interleukin-6. At the same time synthesis of the negative acute-phase protein albumin was reduced to 30% of controls. Half-maximal effects were achieved with 4 units interleukin-6/ml. Interleukin-1 beta had only a partial effect on the regulation of the four patients studied: only a twofold stimulation of alpha 2-macroglobulin and a 60% reduction of albumin synthesis were observed. Tumor necrosis factor alpha did not alter the synthesis of acute-phase proteins. The stimulation of alpha 2-macroglobulin and cysteine proteinase inhibitor synthesis by interleukin-6 was inhibited by interleukin-1 beta in a dose-dependent manner. In pulse-chase experiments the effect of interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha on the secretion of acute-phase proteins was examined. Interleukin-6 markedly accelerated the secretion of total proteins and alpha 2-macroglobulin, whereas the secretion of cysteine proteinase inhibitor, alpha 1-antitrypsin and albumin was not affected. The inhibition of N-glycosylation by tunicamycin abolished the effect of interleukin-6 on the secretion of alpha 2-macroglobulin, indicating a possible role of interleukin-6 on N-glycosylation.
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PMID:Regulation of synthesis and secretion of major rat acute-phase proteins by recombinant human interleukin-6 (BSF-2/IL-6) in hepatocyte primary cultures. 245 86

Tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) play a main role in inducing acute phase protein production by hepatocytes. This study describes the serum levels of TNF alpha and IL-6 in relation to serum levels of C-reactive protein (CRP) and alpha 1-acid glycoprotein (alpha 1AG) in three systemic lupus erythematosus (SLE) patients. Disease courses of these patients were divided in a total of 19 clinical periods, according to the clinical symptoms and interleukin profiles. Significantly elevated TNF alpha levels were found in all but three of the defined periods, without being associated with disease activity. In only four of the defined periods elevated TNF alpha were observed combined with elevated IL-6 and CRP levels. Two of these periods coincided with minor symptoms of SLE, one with an exacerbation and the other one with a systemic infection while SLE activity was low. All other periods showed varying combinations of elevated TNF alpha and/or IL-6 levels being followed or not by elevated CRP levels. Significantly raised alpha 1AG levels were measured in all clinical periods. In most of the observed periods a dissociation was found between TNF alpha and IL-6 and also between the different cytokine (TNF alpha and IL-6) levels and acute phase protein (CRP and alpha 1AG) levels. These data could not be explained by differences in disease course or influences of medication. We conclude that more factors other than TNF alpha and IL-6 must play a role in the regulatory pathway of the acute phase response in SLE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Profiles of cytokines (TNF alpha and IL-6) and acute phase proteins (CRP and alpha 1AG) related to the disease course in patients with systemic lupus erythematosus. 751 Oct 20

Tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) antigenic sites were shown within the resident glomerular mesangial cells of lupus nephritis patients applying the colloidal gold immunocytochemical approach at the electron microscopic level. Using specific polyclonal antibodies against human recombinant (hr) TNF alpha and hrIL-6 in conjunction with the protein A-gold complex, TNF alpha and IL-6 were shown in the mesangial cells, being particularly associated with the membranes of the rough endoplasmic reticulum. In addition, IL-6 also was present in glomerular immune deposits and occasionally in glomerular epithelial cells. In normal renal tissue the TNF alpha and IL-6 immunoreactivities were undetectable. The specific presence of TNF alpha and IL-6 in pathological specimens was shown by several control experiments. Thus, our results offered morphological support that TNF alpha and IL-6 might play a role in human lupus nephritis. The data showed their synthesis by the mesangial cells and their possible participation in the progression to chronicity of the renal injury on secretion.
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PMID:Presence of tumor necrosis factor alpha and interleukin-6 in renal mesangial cells of lupus nephritis patients. 775 Sep 40

Tumor necrosis factor alpha (TNF) is released systematically during the early phase of endotoxin induced fever. To study the effects of this cytokine in guinea pigs, 2 micrograms TNF were intra-arterially injected as a bolus or slowly infused within 60 min. Both modes of administration induced a biphasic elevation of the animals' abdominal temperature lasting 6 h and stimulated the release of endogenous interleukin-6 (IL-6)-like activity. The second phase of the thermal response and the release of endogenous IL-6-like activity were significantly higher, when TNF was slowly infused into the animals' circulation, in spite of a transiently higher TNF-like activity after the bolus injection of TNF. Both TNF and IL-6 may therefore be regarded as candidates to trigger the febrile response in guinea pigs.
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PMID:Changes in body temperature and circulating levels of interleukin-6 after intra-arterial injections or infusions of tumor necrosis factor alpha in guinea pigs. 792 48

Fifty-seven patients with decompensated cirrhosis were studied prospectively to assess the sensitivity and specificity of early clinical or biological signs of bacterial infection. Among them, 19 had proven infection on admission (7 spontaneous bacterial peritonitis, 5 bacteraemia, 3 urinary tract infections, 2 pneumonia, 1 dental abscess and 1 cholangitis). Fever, polymorphonuclear cell count, fibrinogen and C-reactive protein levels were found to be of little or no help in diagnosing bacterial infection on admission. Interleukin-6 plasma levels were, however, significantly different between infected (median: 1386 pg/ml, range: 237-20,000) and non-infected patients (median: 34 pg/ml, range: 0-4500, p < 0.00001). Levels above 200 pg/ml were always found in infected patients, giving a sensitivity of 100% and a specificity of 74%. C-reactive protein correlated weakly with interleukin-6 levels, indicating a defective acute-phase response in cirrhosis. Tumor necrosis factor alpha plasma levels were less sensitive (95%) and specific (68%) for the diagnosis of bacterial infection at a threshold of 50 pg/ml, but were more closely related to a poor patient outcome. In decompensated cirrhosis, interleukin-6 plasma levels on admission provided the most sensitive and specific tool for the diagnosis of bacterial infection.
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PMID:Interleukin-6: an early marker of bacterial infection in decompensated cirrhosis. 793 Apr 84

The aim of this study was to examine if TNF alpha and IL-6 plasma levels could be of value in diagnosing neonatal sepsis. Tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) plasma levels were determined in 15 newborn infants with confirmed sepsis (group I), 18 with suspected sepsis (group II) and 22 control infants (group III). In 33 newborns, initially suspected of having sepsis (groups I and II), a positive test result for plasma concentration of TNF alpha (> 70 pg/ml) had a sensitivity of 73% and a specificity of 94%. A positive test result for IL-6 (> 500 pg/ml) had a sensitivity of 80% and a specificity of 78%. When plasma levels of TNF alpha and IL-6 were combined for the diagnosis of neonatal sepsis, a positive test result for both tests had a sensitivity of 60% and a specificity of 100%. When both tests are positive the diagnosis of neonatal sepsis is almost certain (likelihood ratio = infinity). The combination of TNF alpha and IL-6 determinations appears to be a good predictor of neonatal sepsis.
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PMID:Diagnostic value of plasma levels of tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) in newborns with sepsis. 794 97

The simian immunodeficiency virus SIVsmmPBj14 (SIV-PBj14) is an atypical lentivirus that causes acute disease and death in pig-tailed macaques and in vitro replicates efficiently in resting macaque lymphocytes and activates and induces proliferation of lymphocytes. The present study was conducted to test the hypothesis that production of large quantities of SIV-PBj14 induces widespread immune activation and elaboration of cytokines which lead directly to the death of infected pig-tailed macaques. Following intravenous inoculation of pig-tailed macaques with SIV-PBj14, acute disease developed and was characterized by high levels of plasma viremia, p27gag antigenemia, tumor necrosis factor alpha, and interleukin-6 (IL-6). All animals died within 10 days of infection, at which time some animals had as many as 100% CD4+ cells in the periphery and lymphoid tissues infected. During the last few days before death, titers of infectious virus in blood increased as much as 10(5)-fold. By using dual-label immunofluorescence assays for detection of cell surface activation markers, both CD4+ and CD8+ lymphocytes were shown to express the IL-2 and transferrin receptors following either in vivo or in vitro infection with SIV-PBj14. Furthermore, in vitro infection of quiescent macaque lymphocytes by SIV-PBj14 was accompanied by proliferation of both CD4+ and CD8+ lymphocyte subsets, as measured by incorporation of [3H]thymidine. Increases in numbers of activated lymphocytes and levels of proinflammatory cytokines in plasma coincided with increased amounts of detectable virus in vivo. Clinical signs of disease and pathologic findings were most consistent with death from a shock-like syndrome, in which acute-phase inflammatory cytokines are known to play a major role. Tumor necrosis factor alpha, IL-2, and IL-6 were detected in some cultures infected with SIV-PBj14, but this finding was not consistent. When cytokines were detected, their concentrations were essentially no different from those found in control cultures infected with SIVsmm9, a prototypic strain from which SIV-PBj14 was derived. The in vivo results suggest a synergistic cycle of activation of lymphocytes and monocytes, elaboration of cytokines, and virus production that accelerates uncontrolled and culminates in death. The observed correlations between in vivo and in vitro activation events following SIV-PBj14 infection validate the use of in vitro studies to clarify lentivirus-lymphocyte interactions that may contribute to the virulence of SIV-PBj14.
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PMID:Immune activation and viral burden in acute disease induced by simian immunodeficiency virus SIVsmmPBj14: correlation between in vitro and in vivo events. 805 36


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