Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “IL6”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed2006

Association of the IL6-174(G/C) polymorphism with C-reactive protein concentration after weight loss in obese men.

Elevated plasma concentration of C-reactive protein has emerged as an important predictor of future cardiovascular diseases and metabolic abnormalities in apparently healthy individuals. Obese individuals tend to have elevated C-reactive protein concentrations. Weight loss induces a change in this protein, and single nucleotide polymorphisms in regulating genes might affect this change, since C-reactive protein concentration is known to be approximately 40-50% heritable. Our aim was to study the association between the IL6 -174(G/C), IL1B +3,954(C/T) and CRP +1,059(G/C) single nucleotide polymorphisms, and CRP concentrations in obese men during a weight reduction program. We genotyped 72 obese men who had participated in a weight reduction program. Their C-reactive protein concentrations, interleukin-6 levels and fat mass were determined at two time points: at baseline and after weight reduction (after 2 months). After weight reduction, the mean weight loss was 14.3 kg. Median C-reactive protein concentrations decreased, after weight reduction, from 1.72 to 1.22 mg/l (p < 0.02). The baseline C-reactive protein concentration did not differ between the IL6-174(G/C) genotypes, but after weight loss, concentrations differed (p = 0.03 Kruskal-Wallis test); the highest concentration was found in the CC genotype (CC 1.01 versus GG 1.93 mg/l, p = 0.007 ANOVA post-hoc test). This change in concentration was associated with the IL6-174(G/C) genotype (p = 0.01, Kruskal-Wallis test), being least in the CC genotype. The other single nucleotide polymorphisms studied were not associated with CRP concentrations. Our results show that, at baseline, there is no difference in C-reactive protein concentrations among the different IL6-174(G/C) genotypes, but after weight loss the CC genotype is associated with highest C-reactive protein concentrations, resulting from the fact that C-reactive protein seems not to decrease with weight loss in this genotype.

Adult↗
PubMed1991

Suppression of c-myc and c-myb is tightly linked to terminal differentiation induced by IL6 or LIF and not growth inhibition in myeloid leukemia cells.

Cell proliferation and differentiation are intimately related processes where the proto-oncogenes c-myc and c-myb have been implicated to play a role. Previously, we have shown that both c-myc and c-myb were induced in normal myeloid precursors when the cells were stimulated for growth, were expressed in the autonomously proliferating myeloid leukemic M1 cell line and were rapidly suppressed in both normal and M1 cells following induction of terminal differentiation associated with growth arrest. In order to distinguish molecular events associated with terminal differentiation versus those due to growth inhibition, as well as to increase our understanding of the role of the proto-oncogenes c-myc and c-myb in both of these cellular processes, in this work we have studied the expression of c-myc and c-myb in M1 cells induced for growth inhibition associated with terminal differentiation (via treatment with the physiological inducers IL6 or leukemia inhibitory factor mean value of LIF), partial differentiation (using IL1 or LPS) or no detectable differentiation properties (using IFN beta or IFN gamma). We show that, for all the treatments used in this study, down regulation of the proto-oncogenes c-myc and c-myb occurred only when M1 cells were stimulated to undergo terminal differentiation. In addition, we transfected the M1 cell line with a vector containing the c-myc gene under control of the beta-actin promoter, so that c-myc was no longer down regulated by IL6 or LIF. Previously, we have shown that in the presence of the myeloid differentiation inducers IL6 or LIF, these M1myc cells were blocked at an intermediate stage of myeloid differentiation and continued to proliferate. In sharp contrast to their altered response to IL6 or LIF, M1myc cells were as responsive as the parental M1 cells to growth suppression by the different antiproliferative compounds which do not induce terminal differentiation. Thus, continued expression of c-myc had no effect on growth suppression induced by IL1, IFN beta, IFN gamma and LPS. Taken together, these results indicate that c-myc and c-myb down regulation is not necessary for growth suppression, but down regulation of c-myc is, and c-myb may be, essential for terminal differentiation.

Animals↗
PubMed1995

Modification of M1 cells by exogenous introduction of IL6 gene: a model for gene therapy of acute and chronic myeloid leukemia in mice.

A number of recent studies has shown that animals immunized with cytokine secreting primary tumors show resistance against an unmodified tumor cell challenge. In the present study we have evaluated the potential role of IL6, a myeloid differentiation inducing factor, in modifying myeloid leukemia cells, a tumor so far not challenged by this approach. M1 cells transduced with N2 based retrovirus carrying the murine IL6 gene exhibit morphological and functional alterations. Genetically modified M1 cells show significant reduction in the growth constant coefficient and in the ability to form hematopoietic colonies. Flow cytometry analysis demonstrate increased expression of CD11b, CD18, F4/80, FcR and MHC class II, suggesting driven differentiation towards commitment. Transduced cells secrete high level of autocrine IL6 and, upon activation with LPS, high levels of TNF further indicating a functional alteration and differentiation. The insertion of IL6 gene coding for signals of cell activation and improved expression of MHC antigens into myeloid leukemia cells may enable more effective tumor recognition in vivo, and boost the local as well as the systemic immune-mediated anti-leukemia response.

Acute Disease↗
PubMed1993

[Changes of serum interleukin 6 (IL6) and acute phase protein after hepatectomy in patients with chronic liver disease].

We examined the changes in serum levels of interleukin 6 (s-IL6) and acute phase protein (APP) during perioperative periods in patients with or without chronic liver disease (CLD) who underwent hepatectomy or other surgeries. The elevation of s-IL6 on the first postoperative day was only correlated with preoperative values of indocyanine green retention test (ICG-R15) (r = 0.56, p < 0.01), and not concerned with any operative factors. We divided the patients into the following three groups; the patients with CLD undergoing hepatectomy (n = 21, group A), the patients without CLD undergoing hepatectomy (n = 7, group B), and the patients without CLD undergoing surgeries other than hepatectomy (n = 7, group C). The values of s-IL6 on preoperative day, 1st, 4th, and 7th days after surgery in group A were significantly higher than the corresponding values in group C (p < 0.05). Among the hepatectomy groups, the serum levels of APP on the 4th day after surgery were significantly higher than those on preoperative day. We concluded that the changes in s-IL6 after hepatectomy were strongly concerned with preoperative liver function, especially with values of ICG-R15. However, it seemed that the induction of APP was negatively correlated with the preoperative liver function.

Acute-Phase Proteins↗
PubMed1993

[Specific cytotoxicity of recombinant interleukin 6-pseudomonas exotoxin fusion protein (IL6-PE40) on LT12 leukemic cells expressing high levels of interleukin 6 receptor (IL6R)].

An acute promyelocytic leukemic cell line LT12 was transduced with IL6R cDNA by electroporation. The resultant LT12-IL6R+ leukemic cells expressed more than 1000 IL6R per cell. The effect of the recombinant IL6-PE40 on both the LT12-IL6R+ cells and the IL6R- parental cells (LT12-IL6R-) was studied by leukemic progenitor colony (CFU-L) formation and 3H-TdR incorporation assays. It was found that IL6-PE40 at concentrations ranging from 1 to 1,000 ng/ml inhibited CFU-L formation and DNA synthesis of LT12-IL6R+ cells in a dose-dependent manner. No inhibition was seen at the same concentration range in LT12-IL6R- cells. At concentrations of 250-1000ng/ml, IL6-PE40 led to only 40% inhibition of DNA synthesis in LT12-IL6R- cells. Inasmuch as rIL6 at the same concentrations had no significant effect on both IL6R+ and IL6R- cells, we concluded it is IL6-PE40 that exerts its highly specific killing on leukemic cells expressing high levels of IL6R.

ADP Ribose Transferases↗
PubMed1993

The role of NF-kappa B and NF-IL6 transactivating factors in the synergistic activation of human serum amyloid A gene expression by interleukin-1 and interleukin-6.

To understand the mechanisms by which large increases in serum amyloid A (SAA) occur during the acute phase response, human hepatoma cells were transfected with SAA2 gene reporter plasmids and stimulated with combinations of cytokines. Although interleukin-1 (IL-1) and interleukin-6 (IL-6) stimulated transcription from this promoter individually, addition of both mediators produced a response between two and nine times greater than the expected additive response. This synergistic activation was dependent on the integrity of at least two cis-acting sequences in the SAA2 enhancer. The SAA2 NF-kappa B site was required functionally for the response to both IL-1 and IL-6 alone as well as for synergistic activation; however, IL-6 did not directly induce binding of nuclear proteins to the NF-kappa B sequence. A NF-IL6 site was required for full induction by IL-1 and IL-6, and also mediated strong transactivation by recombinant NF-IL6. Furthermore, transfected NF-IL6 synergized strongly with co-transfected NF-kappa B, particularly with RelA (p65). However synergy between IL-1 and IL-6 was only partly reduced by mutation of the NF-IL6 site, indicating further levels of interaction in addition to the NF-kappa B/NF-IL6 cooperativity.

Base Sequence↗
PubMed1995

Different isoenzyme patterns of nonspecific esterases and the level of IL6 production as markers of macrophage functions.

We examined the isoenzyme patterns of alpha and beta naphtyl acetate esterase and the IL6 production of two macrophage cell lines, which were cloned from a single fusion of macrophage tumor cells and spleen adherent cells. These clones were phenotypically indistinguishable but differ functionally as line 59 presents antigen to Th 1 lymphocytes while line 63 induces suppressor T lymphocytes. Cell extracts of these lines exhibit different isoenzyme patterns of alpha and beta naphtyl acetate esterase at both pH 7.5 and 5.8 but do not differ significantly in the level of produced IL6. Treatment with nitrogranulogen (NG), a derivative of cyclophosphamide, changes the isoenzyme pattern in line 59 and decreases severalfold IL6 production, while in similarly treated line 63 cells isoenzyme pattern remains unaffected but the production of IL6 is significantly increases. We assume that the observed differences between these two cell lines are due to distinct intracellular translation of the membrane signal delivered by NG. The different behaviour of these two parameters can thus be used as a useful tool to further delineate different macrophage subpopulations. We regard it likely that nonspecific esterases may play a role in intracellular processing or trafficking of antigen.

Animals↗
PubMed1997

Variations of IL2, IL6, TNF alpha plasmatic levels in relapsing remitting multiple sclerosis.

We performed a longitudinal analysis of serum IL2, IL6 and TNF alpha concentrations in 40 relapsing remitting MS patients and 20 healthy subjects. Disease activity was quantified by Minimal Record of Disease (M.R.D.) for MS, every 2 or 3 months. IL2, IL6 TNF alpha production was analysed without and with PHA stimulation of whole blood for 2 hours at 37 degrees C. No significant change in IL2 level was found in MS serum. Individual TNF alpha production was significantly increased (P < 0.007) during relapses. The global spontaneous IL6 production was markedly higher in the relapse group than in the control group (P < 0.01) and than in the remission group (P < 0.002) without significant individual variations of cytokine levels regarding the disease activity. Productions of cytokines were enhanced by PHA stimulation, a condition that however suppressed the differences observed without mitogen stimulation. Our data suggest that TNF alpha could be a marker for relapses while IL6 might reflect the global activity of the immune system in MS.

Adult↗
PubMed1996

Improvement by eicosanoids in cancer cachexia induced by LLC-IL6 transplantation.

Cachexia frequently occurs in the late stages of cancer, and is difficult to manage. We previously reported that interleukin-6 (IL-6) cDNA transfection into Lewis lung carcinoma (LLC-IL6) induced cachexia-like symptoms in C57BL/6 mice. This was thought to be a useful experimental model of cancer cachexia. We have examined the effects of two eicosanoids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in order to evaluate whether they could relieve cachexia. LLC-IL6-bearing animals were divided into three treatment groups receiving DHA, EPA or water as the control; 80-microliter samples of these compounds (purity > 95%) were administered orally by catheter daily starting 7 days after tumor transplantation. Tumor growth curves were similar in the three groups. There were no differences in water or food intake in the three groups. However, body weight, a marker of cachexia, was significantly higher in treated mice than in the control group. Sixteen days after tumor transplantation, the mean body weight was 17.45 g (P < 0.05), 17.2 g and 16.41 g in the groups receiving DHA, EPA and water respectively. The eicosanoids did not affect serum levels of IL-6. Ubiquitination of muscle protein, a marker of proteolysis coupled to cachexia, was compared in LLC-IL6- and LLC-transplanted mice. The eicosanoids prevented the ubiquitination of approximately 180 kDa protein. These results suggest that eicosanoids may prevent the cachexia mediated by IL-6.

Animals↗
PubMed1990

Effects of cytokines on human thymic epithelial cells in culture. II. Recombinant IL 1 stimulates thymic epithelial cells to produce IL6 and GM-CSF.

Our earlier study reported the ability of interleukin 1 (IL1) to promote proliferation and to induce morphological changes of human thymic epithelial cells (TEC) in culture. The present study was undertaken to examine the effects of IL1 on the secretory function of TEC. Both human recombinant IL1 alpha and IL1 beta induced TEC to produce molecules in the culture supernatant fluids (TES) which displayed marked thymocyte proliferative capacities. This activity was specifically induced by IL1 since other TEC growth factors such as epidermal growth factor and a bovine pituitary extract had no effect on promoting secretion of T cell-activating molecules by TEC. Using specific radioimmunoassays for both forms of IL1, we found that unstimulated TEC produced negligible amounts of IL1 alpha and IL1 beta in TES, which were not increased by IL1 stimulation, and we concluded that the IL1-induced TES molecules were not IL1. IL1 induced TEC to produce IL6, as detected by the hybridoma growth factor biological activity. Neutralizing anti-IL6 antibodies completely blocked the thymocyte activating capacities of the IL1-induced TES thus implying a major role for IL6 in TEC-derived T cell activation. IL1 also induced TEC to produce GM-CSF as measured by bioassay and confirmed by an immunoenzymetric assay. Our results confirm that TEC are a source of cytokines and show that TEC respond to IL1 by producing cytokines with consequences on the thymic lymphoid population. This further emphasizes the importance and complexity of paracrine molecular interactions involved in intrathymic development.

Antibodies↗
PubMed1992

TNF-mediated IL6 gene expression and cytotoxicity are co-inducible in TNF-resistant L929 cells.

Interleukin (IL)-6 gene induction was studied in the murine cell line, L929r2, which is resistant to the cytotoxic action of tumor necrosis factor (TNF). Increasing concentrations of TNF slightly elevated the background levels of IL6 expression as compared to non-induced cells. Under conditions where the resistant cells are sensitive to TNF by combined TNF/IFN-gamma treatment, the IL6 levels were strongly induced. This induction could be further enhanced by the addition of lithium chloride, or reduced by inhibitors of cytotoxicity, such as dexamethasone. These results confirm our earlier conclusions regarding the close relationship between TNF-mediated IL6 gene expression and the pathway leading to cytotoxicity.

Animals↗
PubMed2006

Association between human African trypanosomiasis and the IL6 gene in a Congolese population.

Despite the importance of behavioural and environmental risk factors, there are arguments consistent with the existence of a genetic susceptibility to human African trypanosomiasis (HAT). A candidate gene association study was conducted in the Democratic Republic of Congo using a family-based sample which included a total of 353 subjects (86 trios; one case and parents (n=258) and 23 families with more than one case and parents (n=95)). Polymorphisms located on the IL1alpha, IL4, IL6, IL8, IL10, TNFalpha and IFNgamma genes were genotyped after re-sequencing of the genes for extensive SNP search. The T allele of the IL6(4339) SNP was significantly associated with a decreased risk of developing the disease (p=0.0006) and a suggestive association was observed for the IL1alpha(5417 T) SNP and an increased risk of developing the disease. These results suggest that genetic variability of the IL6 and to a lesser extent the IL1alpha gene are involved in the development of HAT. For the TNFalpha and IL10 gene polymorphisms, association results obtained here were different from those we observed in another population living under different epidemiologic conditions. This underlines the complexity of the interactions existing between host genetic polymorphisms, parasite diversity and behavioural and environmental risk factors in HAT.

Democratic Republic of the Congo↗
PubMed2002

Organization of the promoter region of the human NF-IL6 gene.

In monocyte/macrophages, the human NF-IL6 gene was activated by LPS or PMA. However, a robust response required stimulation of cells with both LPS and PMA. To examine the molecular basis of this response, we isolated human genomic DNA and determined the nucleotide sequence of a segment (6.4 kb) that included the transcription initiation site of the gene. The unique sequences in the 6.4-kb DNA include several potential transcription factor-binding elements that may explain the molecular basis of the activation of the human NF-IL6 gene by signaling molecules that control the immune and inflammatory responses. Deletion analysis localized an LPS+PMA responsive region downstream position -287, with respect to the transcription initiation site of the NF-IL6 gene. The responsive region includes a potential site for interactions with CREB and a region (-287 to -247) that interacts with SP1 and SP3. In functional assays, the potential CREB site responded to cellular stimulation. The region that interacted with SP1 and SP3 augmented the overall level of activity produced in response to LPS+PMA.

Binding Sites↗
PubMed1999

Dual mechanisms of action of interferon-gamma in potentiating responses to LPS in mice: IL1, TNFalpha and IL6 production in serum and hypothermia.

IFNgamma potentiates the production of serum cytokines and mortality induced by LPS, but these responses do not change in parallel, and the underlying mechanisms are not clear. Pretreatment of mice with 15 microg rrIFNgamma intraperitoneally (IP) resulted in potentiation of LPS-induced serum cytokine production and hypothermia, but these changes depended on the pretreatment time and did not occur in parallel. TNFalpha and IL1beta levels showed peak potentiation after 8-h-IFNgamma pretreatment which may result from a process of sensitization of mechanisms involved in LPS responses. IL6 levels were most markedly potentiated after 3- and 6-h-IFNgamma-pretreatment and hypothermia was markedly potentiated after 0-8 h pretreatments. These effects may result from an additional synergistic action of IFNgamma with other mediators when it is present at significant levels earlier after its injection, given that IFNgamma had little (hypothermia) or no effect (cytokines) alone. The degree of potentiation induced by 18-h-IFNgamma pretreatment was related to the dose of LPS, the maximum response having been increased. Two injections of IFNgamma at 42 and 18 h prior to LPS induced greater increases in TNFalpha and IL1beta production than 18-h pretreatment alone, but not in IL6 production or hypothermia. There may be a maximum level of IL6 production which was surpassed under these conditions. These findings suggest that a balance of sensitizing and synergistic actions of IFNgamma with other mediators such as IL1 and TNFalpha, are the major mechanisms underlying its potentiation of LPS responses in mice.

Animals↗
PubMed1998

The nuclear factor interleukin-6 (NF-IL6) and signal transducer and activator of transcription-3 (STAT-3) signalling pathways co-operate to mediate the activation of the hsp90beta gene by interleukin-6 but have opposite effects on its inducibility by heat shock.

The levels of the 90 kDa heat-shock protein (hsp90) and the activity of the hsp90beta gene promoter are increased in response to treatment by interleukin (IL)-6. The hsp90beta gene promoter contains binding sites for the transcription factors nuclear factor IL-6 (NF-IL6) and signal transducer and activator of transcription 3 (STAT-3), which are activated respectively by the mitogen-activated-protein-kinase and Jak-kinase pathways following IL-6 treatment. Both these factors can activate the hsp90 promoter and have a strong synergistic effect on its activity, which appears to be critical for IL-6-mediated activation of the promoter. Interestingly, the two factors interact differently with the heat-shock factor (HSF) and a heat-shock stress. Thus STAT-3 reduces the stimulatory effect of heat shock whereas NF-IL6 enhances it. When applied together, heat shock and IL-6 produce only weak activation of the hsp90 promoter compared with either stimulus alone, indicating that the inhibitory effect of STAT-3 on HSF predominates under these conditions. In contrast, IL-1, which activates only the NF-IL6 pathway, synergizes with heat shock to produce strong activation of hsp90. These effects are discussed in terms of the multiple stimuli that may regulate the hsp90 promoter in unstressed cells and their interaction with its stress-mediated activation.

CCAAT-Enhancer-Binding Proteins↗
PubMed1992

The p50 subunit of NF-kappa B associates with the NF-IL6 transcription factor.

The NF-kappa B-p50 polypeptide, a member of the Rel family of transcription factors, was produced as a fusion protein containing amino-terminal peptide additions that facilitate purification and detection with a monoclonal antibody and specific radiolabeling by phosphorylation in vitro. The 32P-labeled NK-kappa B-p50 fusion polypeptide was used as the probe in Western blotting experiments and in screenings of a bacteriophage expression library to isolate cDNAs encoding interacting protein domains. As expected, cDNAs encoding proteins of the Rel family were identified. Surprisingly, the 32P-labeled NF-kappa B protein also specifically bound to proteins encoded by cDNAs for the human NF-IL6 transcription factor. The NF-kappa B-p50 and NF-IL6 proteins directly interact, and the Rel homology domain and leucine-zipper motif, respectively, are important for this interaction. Since induction of the NF-kappa B and NF-IL6 factors are important events in immune and acute-phase responses, this interaction could permit coregulation of genes.

Amino Acid Sequence↗
PubMed2003

Interleukin-6 (IL6) genotype is associated with fat-free mass in men but not women.

We studied the association of the G-174C promoter polymorphism in the interleukin-6 gene (IL6) with total body fat and fat-free mass (FFM) in 242 men and women (IL6 genotypes: G/G, n = 87; G/C, n = 100; C/C, n = 55) across the adult age span (21-92 years). In men, but not women (significant genotype by sex interactions; p =.023-.048), the C/C group exhibited significantly lower total FFM than the G/G group (54.7 +/- 0.8 kg vs 57.2 +/- 0.7 kg, respectively, p =.020), as well as significantly lower FFM of the lower limbs compared with the G/G group (18.4 +/- 0.3 kg vs 19.8 +/- 0.3 kg, respectively, p =.004). No significant genotype differences were observed in total body fat mass in either men or women. The results indicate that the IL6 G-174C polymorphism is significantly associated with FFM in men but not women.

Adult↗
PubMed1991

Haemodialysis membranes modulate chronically the production of TNF alpha, IL1 beta and IL6.

As cytokines may play a role in the adverse effects of haemodialysis, TNF alpha, IL1 beta and IL6 were investigated before the haemodialysis session (chronic effect) and after 30 and 60 min (session effect). We found that haemodialysis exerts a chronic effect on cytokines but the type of haemodialysis membrane, Cuprophan or Hemophan, specifically influences each cytokine. Circulating levels of TNF and unstimulated production of TNF and IL1 by monocytes were increased in patients dialysed with Hemophan, whereas a greater LPS-stimulated production of TNF was observed in patients dialysed with Cuprophan. Both types of membrane induced a higher production of IL6 as compared to controls. The alternate use of Cuprophan and Hemophan demonstrated that the production of TNF and IL1 was dependent on the type of haemodialysis membrane. We also found that Cuprophan induced a reversible decrease of spontaneous and LPS-stimulated production of TNF, IL1 and IL6 during the haemodialysis session. Taken together, these results suggest that Hemophan induced a sustained production of cytokines whereas Cuprophan primed monocytes, probably through the activation of the complement pathway.

Aged↗