UNIPROT:P05231 - FACTA Search

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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of the induction of pulmonary phospholipidosis by amiodarone on selected pulmonary host defense functions was studied in male Fischer-344 rats. One week of daily amiodarone treatment resulted in a 4.5-fold increase in total phospholipid in alveolar macrophages recovered from the lungs by bronchoalveolar lavage. The presence of the phospholipidosis had no effect on the phagocytosis of heat-killed yeast cells, the induction of luminol-dependent chemiluminescence, or the spontaneous release of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), or spontaneous and LPS-stimulated release of IL-1 by alveolar macrophages in vitro. In contrast, the LPS-stimulated release of IL-6 and TNF-alpha by phospholipidotic alveolar macrophages was enhanced compared with control cells. The pulmonary clearance of Listeria monocytogenes following intratracheal administration of the bacteria was not affected by the phospholipidotic condition. It appears that, in the context of the functions studied, the induction of pulmonary phospholipidosis by amiodarone does not impair pulmonary host defense processes in rats, and may actually be associated with the augmentation of some activities.
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PMID:Effects of amiodarone-induced phospholipidosis on pulmonary host defense functions in rats. 861 40

Interleukin-10 (IL-10), like IL-4, is known to inhibit cytokine expression in activated human monocytes. We showed that both IL-10 and IL-4 inhibit LPS-induced IL-6 mRNA and protein expression by inhibiting the transcription rate of the IL-6 gene. The strong inhibition of the IL-6 transcription rate prompted us to study the effect of IL-10 and IL-4 on the expression of transcription factors. We questioned whether or not IL-10 and IL-4 affected the expression of transcription factors that are known to be involved in the control of the IL-6 transcription rate, namely activator protein-1 (AP-1), nuclear factor IL-6 (NF-IL6), and nuclear factor kappa B (NF-kappaB). In electrophoretic mobility shift assays (EMSAs) we showed that IL-10 and IL-4 inhibited LPS-induced AP-1 binding activity. The inhibiting effect of IL-4 was slightly more pronounced than that of IL-10. Downregulation of LPS-induced AP-1 was accompanied, and thus possibly explained, by a reduced expression at mRNA level of the two major components of the AP-1 complex, namely c-fos and c-jun as determined by Northern experiments. Binding activity of NF-IL6 was also strongly inhibited by IL-4 whereas IL-10 showed no effect. NF-IL6 mRNA levels were not affected by IL-10 or IL-4, suggesting that IL-4 affects binding activity of preexisting NF-IL6. Neither IL-10 nor IL-4 inhibited LPS-induced NF-kappa B binding activity. In agreement with this finding, Northern experiments where p65 and p105 mRNA levels were determined, demonstrated that expression of these components of the NF-kappa B transcription factor were not affected by IL-10 or IL-4. Furthermore, neither IL-10 nor IL-4 showed any effect on I-kappa B mRNA expression as determined by Northern experiments. Thus, IL-10 and IL-4 similarly affect IL-6 expression. However, for IL-4 this was accompanied with a reduction of AP-1 and NF-IL6 binding activity whereas IL-10 only inhibited AP-1 binding activity.
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PMID:Effects of IL-10 and IL-4 on LPS-induced transcription factors (AP-1, NF-IL6 and NF-kappa B) which are involved in IL-6 regulation. 870 36

Recent studies have suggested that substance P (SP) and some other neuropeptides are able to induce the synthesis of the proinflammatory cytokines interleukin-1 (IL-1) and interleukin-6 (IL-6) in peripheral blood mononuclear cells. In the present study, we re-examined these findings by using a completely endotoxin-free monocyte cultivation system. We demonstrate that the neuropeptides SP, vasoactive intestinal peptide, substance K. cholecytokinine, alpha-endorphin and beta-endorphin are consistently unable to induce the synthesis of IL-1 and IL-6 in human peripheral blood monocytes. However, low amounts of LPS (1 pg/ml) synergized with SP to induce IL-6 mRNA expression. In contrast to its lack of effect in monocytes, we were able to confirm the ability of SP to induce cytokine synthesis in astrocytic cells. Our results raise questions about previous results claiming a neuropeptide-induced synthesis of proinflammatory cytokines in human monocytes. In conjunction with other studies, we suggest that undetected levels of endotoxin/LPS in the culture medium may have been primarily responsible for results suggesting an inductive effect of neuropeptides on cytokine synthesis in monocytes.
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PMID:Effects of substance P and selected other neuropeptides on the synthesis of interleukin-1 beta and interleukin-6 in human monocytes: a re-examination. 876 29

Phagocyte-derived interleukin-12 (IL-12) is a proinflammatory cytokine promoting cell-mediated immune responses in inflammatory and infectious disorders. Based on sequence homology of the p40 subunit with the interleukin-6 receptor it has been speculated that IL-12 could also exist as a membrane-bound form, but thus far only soluble (secreted) IL-12 has been identified. We have therefore analyzed human monocytic U937 and mouse P388D1 macrophages for membrane-bound IL-12 by flow cytometry. IL-12 is constitutively expressed on the cell surface of both cell lines. IL-12 cell surface staining is enhanced in response to stimulation with IFN-gamma plus LPS. IL-12 is also present in the supernatant of cultured P388D1 macrophages. Thus, in addition to a soluble form IL-12 occurs as a membrane-bound molecule on monocyte/macrophage cell lines.
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PMID:The proinflammatory cytokine interleukin-12 occurs as a cell membrane-bound form on macrophages. 878 Jul 34

Endotoxemia initiates a cytokine response that is thought to mediate the syndromes of sepsis and multiple organ failure. This study measured cytokine levels in the blood and airways of rats at critical time points during the development of lung injury induced by chronic endotoxin (LPS) infusion in the rat. Tumor necrosis factor-alpha (TNF), interleukin-1-beta (IL-1), and interleukin-6 (IL-6) were measured in the blood and bronchoalveolar lavage fluid (BALF) of endotoxemic and control animals. BALF was also studied for the percentage of neutrophil (PMN) count and chemotactic activity. Lung histology was determined at 72 h following infusion of LPS. Chronic endotoxemia of > or = 48 h but not < or = 24 h resulted in severe acute lung injury (ALI). Circulating levels of TNF and IL-1 were only transiently elevated, whereas IL-6 remained elevated in the endotoxemic rats. TNF, IL-1, and IL-6 levels in BALF were only transiently elevated. Chemotactic activity, levels of cytokine-induced neutrophil chemoattractant (CINC), and the percentage of PMN counts in BALF all increased significantly by 36 h. Other potential chemoattractants; leukotriene B4 and transforming growth factor-beta were not elevated in BALF. In conclusion, severe ALI requires a minimum of 48 h LPS infusion in this model and is associated with high levels of circulating IL-6, increased CINC activity, and an increased percentage of PMN count in BALF. Local inflammatory events may be as important as the systemic cytokine milieu in mediating ALI. The signal for these local events does not appear to depend solely on the transient elevations of circulating TNF and IL-1 at the onset of endotoxemia, although sustained high levels of IL-6 may be important.
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PMID:Acute lung injury in endotoxemic rats is associated with sustained circulating IL-6 levels and intrapulmonary CINC activity and neutrophil recruitment--role of circulating TNF-alpha and IL-beta? 882 83

Three different procedures were used to isolate lipopolysaccharides from the Salmonella enteritidis strain 477: phenol-water extraction with ethanol precipitation (LPS 1), phenol-water extraction with methanol precipitation (LPS 2) and FPLC purification (LPS 1/1). Production of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) was observed in the supernatants of adherent spleen cells of BALB/c mice after the stimulation and cultivation of the cells. The quantity of IL-1 beta and IL-6 depended on the method of LPS isolation. The highest level of IL-1 beta was recorded at LPS 2, and of IL-6 at the stimulation of cells by means of LPS 1.
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PMID:Production of IL-1 beta and IL-6 by adherent spleen cells after the stimulation with lipopolysaccharides from Salmonella enteritidis strain. 887 94

n-3 polyunsaturated fatty acids (PUFA) can affect several monocyte functions and the biochemistry of blood cells, thus possibly influencing the initiation of thrombosis, inflammatory disease and atherosclerosis. In this study, we have investigated the effect of dietary supplementation with n-3 PUFA ethyl esters on procoagulant activity (PCA) and interleukin-6 (IL-6) production by human mononuclear cells. Nine healthy volunteers received 4 g/d of n-3 PUFA ethyl esters (4 x 1 g capsules with at least 85% eicosapentaenoic + docosahexaenoic acid ethyl esters) for 18 weeks. Before and at the end of the treatment, mononuclear cells were obtained from peripheral citrated blood by Ficoll-Hypaque density gradient centrifugation. Cellular suspensions (10(7) cells/ml) were incubated at 37 degrees C for 4 h in the absence and presence of lipopolysaccharide (10 micrograms/ml); PCA was determined by one-stage clotting assay and IL-6 concentrations were assayed in supernatants by specific ELISA. After 18-week treatment, both unstimulated and stimulated monocyte PCA were significantly reduced by 66% and 63%, respectively (P < 0.01). Similarly, a significant inhibitory effect by n-3 PUFA treatment on basal and LPS-stimulated IL-6 monocyte production was observed (50% and 46%, respectively, P < 0.05). These data indicate that 18-week n-3 PUFA supplementation may influence monocyte activities, which play a specific role in atherosclerosis and its thrombotic complications.
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PMID:n-3 PUFA supplementation, monocyte PCA expression and interleukin-6 production. 888 56

Inhalation of swine-house dust may cause an acute airway inflammatory condition (organic dust toxic syndrome). Thirty-eight healthy subjects were exposed to swine dust while weighing swine for 3 h. We studied the correlation between acute health effects and the inhaled bacterial exposure markers peptidoglycan (the main constituent of the cell walls of gram-positive bacteria, but also present in lesser amounts in gram-negative bacteria) and lipopolysaccharides (LPS; present only in gram-negative bacteria). LPS activity in airborne dust was measured with the Limulus amebocyte lysate assay (LPS(LAL)), and the total LPS was estimated from 3-hydroxy fatty acids, which were measured with gas chromatography-mass spectrometry (GC-MS) (LPS(GC-MS)). Peptidoglycan was estimated from muramic acid measured with GC-MS. The median (25th to 75th percentile) concentration of inhalable dust was 21 (16 to 25) mg/m3. LPS(LAL) was 1.2 (0.9 to 1.4) microg/m3; LPS(GC-MS) was 3.9 (2.5 to 4.9) microg/m3; and the peptidoglycan concentration in airborne dust was 6.5 (2.7 to 13) microg/m3. All exposure markers correlated significantly with an increase in serum interleukin-6. LPS(LAL) showed the highest correlation (r2 = 0.29) and total inhaled dust the lowest (r2 = 0.09). LPS(LAL) also correlated with symptoms and with an increase in bronchial responsiveness and decrease in vital capacity (VC). Peptidoglycan, but not LPS(LAL), correlated with an increase in the blood granulocyte concentration and in body temperature. The results suggest that several microbial agents in inhaled swine-house dust may contribute to acute systemic health effects.
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PMID:Exposure to bacteria in swine-house dust and acute inflammatory reactions in humans. 891 33

Interleukin-6 (IL-6) administration to human subjects or experimental animals induces changes in thyroid hormone metabolism resembling those in the sick euthyroid syndrome. Furthermore, the decrease in serum T3 during illness is significantly related to serum IL-6 concentrations. These findings suggest, but do not prove, a causal role for IL-6 in the development of the low T3 syndrome. The aim of the present study was to evaluate the role of IL-6 in the development of the sick euthyroid syndrome in IL-6 knock-out (IL-6(-/-)) mice compared to that in wild-type mice (IL-6(+/+)). Illness was induced in IL-6(-/-) and IL-6(+/+) mice by 1) administration of bacterial endotoxin (LPS), 2) infection with Listeria monocytogenes, and 3) turpentine injection in both hind limbs. Food intake was kept similar in both groups in all three experiments. Serial measurements were made of serum IL-6, tumor necrosis factor-alpha, T3, T4, corticosterone, and liver 5'-deiodinase (5'-DI) messenger RNA (mRNA) for 24 h (LPS), 96 h (L. monocytogenes), and 48 h (turpentine). Serum IL-6 increased in response to all stimuli in IL-6(+/+) mice, but not in IL-6(-/-) mice. Serum tumor necrosis factor-alpha was induced by LPS in both groups to a similar extent, but did not rise after L. monocytogenes or turpentine administration. Serum T3 and T4 decreased after all three stimuli. The decrease in serum T4 in IL-6(-/-) was similar to that in IL-6(+/+) mice. The decrease in serum T3, however, was smaller in the IL-6(-/-) mice than in the IL-6(+/+) mice; T3 levels were 1.56 +/- 0.29 and 0.99 +/- 0.15 nmol/liter, respectively, 24 h after LPS treatment (P < 0.01), 2.39 +/- 0.17 and 1.75 +/- 0.24 nmol/liter 96 h after L. monocytogenes treatment (P < 0.01), and 1.46 +/- 0.18 and 1.10 +/- 0.25 nmol/liter 48 h after turpentine treatment (P < 0.05). The smaller fall in serum T3 in IL-6(-/-) mice could not be attributed to differences in the severity of the induced illness, food intake, or corticosterone response, which were all similar in IL-6(-/-) mice and IL-6(+/+) mice. Liver 5'-deiodinase mRNA decreased after all three stimuli; the decrease after LPS and L. monocytogenes infection was smaller in the IL-6(-/-) mice, but the difference in IL-6(+/+) mice just failed to reached statistical significance. Liver 5'-deiodinase activity after turpentine injection administration decreased in the wild-type animals by 36%, but did not change in the knock-out mice. In conclusion, acutely induced illness generates the low T3 syndrome, which is less marked in IL-6 knock-out mice than in wild-type mice. The data suggest a causal role of IL-6 in the development of the low T3 syndrome.
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PMID:Induced illness in interleukin-6 (IL-6) knock-out mice: a causal role of IL-6 in the development of the low 3,5,3'-triiodothyronine syndrome. 894 Mar 42

The major target organ for Hepatitis B Virus (HBV) is the liver, but extrahepatic sites including monocytes express receptors for HBV and may become infected. Therefore, we investigated the effect of HBV on the in vitro expression of interleukin-beta (IL-1 beta) and interleukin-6 (IL-6) by the monocytoid cell line THP-1, exposed to various stimuli (LPS, PMA or both). Nonstimulated THP-1 cells did not synthesize IL-1 beta and IL-6, even after in vitro exposure to HBV. LPS stimulation alone induced moderate secretion of both IL-1 beta and IL-6 (300 pg/ml). After induction of macrophage differentiation by PMA, THP-1 cells acquired adherence and expressed a higher level of IL-1 beta (up to 2 ng/ml) but did not synthesize IL-6. Treatment of THP-1 cells with PMA and LPS caused the highest production of both IL-1 beta and IL-6 (> 5ng/ml). In vitro exposure of PMA + LPS-stimulated THP-1 cells to HBV resulted in secretion of both HBsAg and preS2Ag which was maintained over 10 days of culture. Southern blot technique was used to study the state of HBV DNA in the cells. Hybridization of non-digested cellular DNA showed only high molecular weight HBV DNA forms. The HindIII restriction pattern revealed bands corresponding to large DNA fragments and the presence of bands at the 3.2 kb position. Under these conditions (PMA + LPS), HBV inhibited the production of IL-1 beta and IL-6 proteins and completely suppressed the IL-1 beta and IL-6 mRNA. Thus, our findings (i) strongly support a relationship between the state of cell differentiation and susceptibility of cells to HBV infection, and (ii) demonstrate that HBV exerts an inhibitory effect on the induction of IL-1 beta and IL-6 genes expression in monocytic THP-1 cells. These results suggest that HBV leads to a fall of pro-inflammatory cytokine production by monocytes/macrophages, which may contribute to impaired host immune response during infection.
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PMID:Suppressive effect of hepatitis B virus on the induction of interleukin-1 beta and interleukin-6 gene expression in the THP-1 human monocytic cell line. 901 Jun 83

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