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)

We have analysed the prognostic information for survival of presenting features in an unselected series of 394 myeloma patients. 15 variables with significant prognostic information were identified, among these were some not previously or only recently reported: serum levels of hepatocyte growth factor (HGF), interleukin-6 (IL-6), C-terminal cross-linked telopeptide of collagen I (ICTP) and soluble interleukin-6 receptor (sIL-6R). In a multivariate Cox analysis six variables were significantly and independently associated with poor survival: high age, low W.H.O.-performance status (PS), high serum levels of calcium, beta-2-microglobulin (beta-2M), IL-6 and sIL-6R. A risk score formed to predict survival for each percentile of the patient population allowed an efficient separation of prognostic groups. The discriminating power of the model compared favourably with three other previously published staging systems applied to the study population. Exclusion of IL-6 and sIL-6R from the model only marginally decreased the efficacy of the separation. The predictive value of some variables (sIL-6R, beta-2M and W.H.O.-PS) decreased significantly over time. We conclude that formation of a risk score based on independent variables is an efficient way to separate prognostic groups, that the contribution of new and not easily available parameters should be thoroughly evaluated before inclusion in prognostic models for clinical use and that the predictive value of parameters may decrease over time.
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PMID:Prognostic evaluation in multiple myeloma: an analysis of the impact of new prognostic factors. 1052 4

Chronic intermittent injection of carbon tetrachloride (CCl4) for more than 10 weeks induced liver fibrosis in mice, as evidenced by positive Azan staining and increased intrahepatic collagen content. Preceding the onset of liver fibrosis, interleukin-6 (IL-6) gene expression was enhanced in liver and immunoreactive IL-6 was detected in infiltrating inflammatory cells. To delineate the role of IL-6 in this process, we treated IL-6-deficient mice with CCl4 in a similar manner for 12 weeks, after which fibrotic changes were less evident and serum albumin levels were lower in IL-6-deficient than wild-type mice. Moreover, CCl4-induced expression of transforming growth factor beta1 and hepatocyte growth factor genes in liver was significantly reduced in IL-6-deficient mice. Thus, IL-6 may be vitally involved in fibrotic changes and maintenance of serum albumin levels, partly by modulating intrahepatic expression of these cytokines.
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PMID:Attenuated liver fibrosis and depressed serum albumin levels in carbon tetrachloride-treated IL-6-deficient mice. 1053 16

We examined the effect of parathyroid hormone and various signaling molecules on collagen synthesis and chloramphenicol acetyltransferase activity in cultured transgenic mouse calvariae carrying fusion genes of the rat Col1a1 promoter and the chloramphenicol acetyltransferase reporter. After 48 h of culture, parathyroid hormone, forskolin, dibutyryl cAMP, 8-bromo cAMP, and phorbol myristate acetate inhibited transgene activity, while the calcium ionophore ionomycin had no effect. Pretreatment of calvariae with the phosphodiesterase inhibitor isobutylmethylxanthine potentiated the inhibitory effect of 1 nM parathyroid hormone on transgene activity and collagen synthesis. Parathyroid hormone further inhibited transgene activity and collagen synthesis in the presence of phorbol myristate acetate. Parathyroid hormone inhibition of transgene activity and collagen synthesis was not affected by indomethacin or interleukin-6. After 48 h of culture, parathyroid hormone inhibited chloramphenicol acetyltransferase activity by 50-85% in cultured calvariae carrying transgenes having progressive 5' upstream deletions of promoter DNA down to -1683 bp. These data show that the inhibitory effect of parathyroid hormone on Col1a1 expression in mouse calvariae is mediated mainly by the cAMP signaling pathway. Prostaglandins and IL-6 are not local mediators of the parathyroid hormone response in this model. Finally, regions of the Col1a1 promoter downstream of -1683 bp are sufficient for parathyroid hormone inhibition of the Col1a1 promoter.
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PMID:Parathyroid hormone inhibits collagen synthesis and the activity of rat col1a1 transgenes mainly by a cAMP-mediated pathway in mouse calvariae. 1067 25

Keloids are characterized by a net accumulation of collagen. To date, the role of growth factors and various cytokines in the pathogenesis of these lesions has not been fully characterized. Interleukin-6 (IL-6) is an important immunoregulatory cytokine that has been implicated in a number of fibrotic autoimmune diseases such as scleroderma, interstitial nephritis, and pulmonary interstitial fibrosis. However, the role of IL-6 in the development of keloids has yet to be defined. This study demonstrates increased expression of the IL-6 gene in fibroblasts isolated from patients with keloids when compared with control fibroblasts using the ribonuclease protection assay. Subsequent detection of increased levels of IL-6 secretion by keloid fibroblasts is also demonstrated under unstimulated and stimulated conditions using serum and interferon gamma (IFN-gamma) (unstimulated: 0.3694 + 0.2499 pg/cell vs 0.0662 + 0.0786 pg/cell, P = 0.0137; serum: 1.066 + 0.513 pg/cell vs 0.233 + 0.231 pg/cell, P = 0.0027; serum and IFN-gamma: 1.286 + 0.395 pg/cell vs 0.244 + 0.199 pg/cell, P < 0.0001). These results suggest that IL-6 may play a significant role in the pathogenesis of keloids.
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PMID:Elevated interleukin-6 expression in keloid fibroblasts. 1072 Apr 55

Oral submucous fibrosis (OSF) is a pre-malignant fibrotic lesion of the mouth in betel quid chewers and is characterised by dense bands of collagen in the juxta-epithelial region preceded by inflammation. We have investigated the spontaneous and stimulated production of cytokines by peripheral blood mononuclear cells (PBMC) from OSF patients and compared them with genetically-related relatives, Indian and Caucasian control subjects. The cytokines studied included: interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). The results show: a) significant differences in the stimulated versus non-stimulated levels of IL-1beta, IL-6, IL-8 and TNF-alpha but not of IFN-gamma production by patients, and in the relatives' stimulated versus non-stimulated levels of IL-1beta, IL-6 and IFN-gamma; b) no difference in the spontaneous cytokine production between any two groups; and c) significant increases in the patients' stimulated cytokines compared to the Caucasian and Indian controls (P< or =0.050). These results demonstrate increased levels of proinflammatory cytokines and reduced anti-fibrotic IFN-gamma in patients with OSF, which may be central to the pathogenesis of OSF.
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PMID:Oral submucous fibrosis patients have altered levels of cytokine production. 1073 39

Hypertrophic burn scars (HBSs) are characterized by a net accumulation of collagen. The role of growth factors and various cytokines in the pathogenesis of these lesions has not been fully characterized. Interleukin-6 (IL-6) is an important immunoregulatory cytokine that can affect fibroblast function. This study showed increased expression of the IL-6 gene in fibroblasts isolated from patients with HBSs compared with control fibroblasts when the ribonuclease protection assay was used. A subsequent increase in unstimulated and stimulated IL-6 secretion was noted in HBS fibroblasts compared with normal control fibroblasts (unstimulated, 0.3627+/-0.2017 pg/cell vs 0.0662+/-0.0786 pg/cell, P = .0054; serum, 0.770+/-0.523 pg/cell vs 0.233+/-0.231 pg/cell, P = .0381; serum and interferon-gamma, 0.912+/-0.650 pg/cell and 0.244+/-0.199 pg/cell, P = .0327). These results are further evidence of the role of inflammatory cytokines in the development of HBSs.
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PMID:Altered interleukin-6 expression in fibroblasts from hypertrophic burn scars. 1075 47

In order to evaluate whether or not polyethylene terephthalate coated with pyrolytic carbon and collagen (PET+PC) favors inflammatory or hyperplastic reactions, the expression of mRNAs specific for interleukin-6 (IL-6), platelet-derived growth factor-A (PDGF-A), PDGF-B, transforming growth factor-beta1 (TGF-beta1), and TGF-beta2 were tested in vitro by cultured human umbilical vein endothelial cells (HUVEC). The cultures were put in contact with PET+PC for 1, 24, 48, and 72 h. The same cells cultured on polystyrene without biomaterials were tested as negative controls; cultures incubated with LPS were the positive control. The expression of mRNAs was evaluated by RT-PCR with specific primers. PET+PC did not determine any differences in the expression of IL-6-specific mRNA at any of the incubation times compared to the negative control while LPS (the positive control) induced expression after 24, 48, and 72 h. PET+PC induced a more precocious expression of mRNA specific for PDGF-A than did the negative control; however, the expression no longer was present after 48 h while in the negative control the expression stopped after 72 h. PET+PC induced a less frequent expression of PDGF-B-specific mRNA than did the negative control and LPS, especially after 24 h. PET+PC induced a later expression of TGF-beta2-specific mRNA than did the negative control and a less frequent expression of mRNA specific for TGF-beta1 after 24 and 72 h.
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PMID:Cytokine expression in vitro by cultured human endothelial cells in contact with polyethylene terephthalate coated with pyrolytic carbon and collagen. 1075 6

We analyzed the changes in the serum levels of both interleukin-6 (IL-6), human hepatocyte growth factor (h-HGF), and type IV collagen 7S (7S) during the perioperative period of a hepatectomy and evaluated their relationship with systemic inflammatory response syndrome (SIRS). The study subjects consisted of 40 patients who underwent a hepatectomy. In 14 out of 40 patients, postoperative SIRS(+) was observed. Between the SIRS(+) and SIRS(-) cases, there were significant differences in the preoperative values of prothrombin time, hepaplastin test, cholinesterase, and indocyanine green retention at 15 min (P < 0.01). Compared with the SIRS(-) cases, the IL-6, h-HGF, and 7S of the SIRS(+) cases fluctuated in a higher range and remained significantly higher after postoperative day 1 (P < 0.05). Eight out of 14 SIRS(+) patients had postoperative complications. In the 8 SIRS(+) patients with postoperative complications and in the 4 patients in which the SIRS(+) state lasted 3 days or longer, the 7S levels were significantly higher during the perioperative period (P < 0.05). In the SIRS(+) cases, the postoperative levels of IL-6 and h-HGF, as well as pre- and postoperative levels of 7S, were elevated. We therefore consider these levels to be risk factors for complications during the perioperative period of a hepatectomy.
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PMID:Significant changes in the serum levels of IL-6, h-HGF, and type IV collagen 7S during the perioperative period of a hepatectomy: relevance to SIRS. 1081 74

Although parathyroid hormone (PTH) has the ability to stimulate bone growth in both rats and humans, its mechanism of action is not fully understood at the molecular level. An in vitro marker that reflects the in vivo anabolic actions of PTH would facilitate the discovery of small-molecule compounds that stimulate bone growth. We therefore compared the patterns of gene expression in three cell lines treated with PTH. The levels of c-fos, collagenase, interleukin-6 (IL-6), and collagen mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR) in three osteoblast-like cell lines. The most responsive marker was c-fos, which was induced 5-10-fold after 1 h of PTH treatment in the UMR106-01 cell line. Because it is a critical early response gene in bone growth, we investigated the possibility of using c-fos stimulation as a method to screen for compounds that can stimulate bone formation. A highly sensitive, medium-throughput RT-PCR assay for c-fos mRNA expression was established using the Taqmantrade mark Detection System (Perkin Elmer, Mississauga, Ontario). Cells were treated with a series of compounds to determine the specificity of c-fos stimulation. Of the compounds tested, only PTH, prostaglandin E(2), 8-bromo-cAMP, and forskolin induced c-fos mRNA levels, indicating that this assay was specific for compounds that are known to induce cAMP and stimulate bone growth. These results indicate that a simple in vitro assay for c-fos may be a reliable method for the screening of compounds that stimulate bone growth in vivo.
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PMID:Development of an In Vitro Screening Assay for Compounds that Increase Bone Formation. 1083 33

Matrix metalloproteinases (MMPs) in the synovial fluid are responsible for collagen breakdown during physiologic cartilage turnover and the pathologic destruction of the cartilage. We measured the levels of MMPs, specific tissue inhibitors of metalloproteinases (TIMPs), and interleukin-6 (IL-6) in synovial fluid from the knees of 36 patients with cartilage lesions subdivided according to severity based on arthroscopic findings. Lesions were classified as mild (group 1, edema with no disruption of the surface), moderate (group 2, open lesions without exposure of subchondral bone), or severe (group 3, exposure of subchondral bone). Zymography (gel electrophoresis in the presence of hydrolizable substrates) showed a 60-kd band in all samples. A second band (94-kd) was found exclusively in specimens from groups 2 and 3, and a third band (110-kd) was present only in group 3. Concentrations of 2 of the most important modulators of MMP activity, TIMP-1 and IL-6, were measured. TIMP-1 levels did not vary significantly with the severity of cartilage damage. Linear regression analysis revealed a significant positive correlation between TIMP-1 and IL-6 in groups 1 and 2. These data indicate that the severity of the cartilage damage corresponds with MMP activity. The correlation between IL-6 and TIMP-1 in groups with mild and moderate damage suggests a regulating mechanism that is absent in severe lesions.
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PMID:Correlation between osteoarthritic cartilage damage and levels of proteinases and proteinase inhibitors in synovial fluid from the knee joint. 1153 4


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