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 studied the effect of cyclosporine A, prednisolone, and the Ca2+ channel blocker verapamil on interleukin-6 binding to mitogen-activated peripheral blood mononuclear cells, using a flow cytometric technique and phycoerythrin-conjugated IL-6. All mitogenic stimuli up-regulated IL-6 binding to a variable degree. PHA alone or in combination with PMA was the most effective stimulant in up-regulating IL-6 binding in all the experiments performed. The main changes in IL-6 binding were seen in the large cell cluster, which consisted mainly of lymphoblasts. PHA and PHA/PMA, however, also up-regulated the mean fluorescence intensity on the small cell cluster, which consisted mainly of quiescent lymphocytes. The overall effect of the three pharmacological agents on mitogen-up-regulated IL-6 binding was minimal; most significant were a down-regulation by all three agents of IL-6 binding by small lymphocytes in PHA/PMA cultures, a down-regulation of IL-6 binding by CsA in PHA/PMA-induced large PBMC, and an up-regulation by verapamil of PMA-induced IL-6 binding in large PBMC. Measurements of IL-2 binding and of IL-6 production in the same cultures showed a different pattern than that seen with IL-6 binding, as well as different CsA, prednisolone, and verapamil action. In conclusion, by using a new flow cytometric technique providing information both about the quantity of bound cytokine and about the proportion of IL-6-binding cells, we have demonstrated that IL-6 receptor expression in vitro by PBMC can be up-regulated by the use of stimulants differing in the signal transduction pathways they activate. In addition, by using different pharmacological agents and stimuli to dissect different activation pathways of the in vitro immune response, we conclude that IL-6R generation is regulated differently from IL-6 production. Furthermore, since CsA and prednisolone are known inhibitors of in vitro IL-2 production, our results indicate that IL-6R generation does not rely exclusively on the presence of IL-2.
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PMID:Binding of phycoerythrin-conjugated interleukin-6 to in vitro-activated human peripheral blood mononuclear cells--effect of immunosuppressive agents and of a calcium channel blocker. 149 42

A porcine interleukin-6 (pIL-6) cDNA has been cloned from pig spleen cDNA library to provide information that would allow us to study IL-6 mRNA expression during pregnancy of several domestic Artiodactyla. The cDNA is 1058 bp long and with a single open reading frame that encodes a 212 amino acid polypeptide with 28-residue signal sequence. It shares 61% and 43% amino acid sequence identity with human and mouse IL-6, respectively. PCR procedures with primers designed from regions of sequence conserved between human and pig have been used to identify IL-6 cDNA in lambda gt11 libraries constructed from day 15-16 (sheep), day 17 (cattle), and day 13-17 (pig) conceptus mRNA. The presence of IL-6 mRNA in elongating preimplantation ovine (days 13-25), porcine (days 13-21), and bovine (days 16-20) conceptuses was also demonstrated by PCR after reverse transcription of total ribonucleic acid with reverse transcriptase and by solution hybridization with a pIL-6 cRNA probe. These observations suggest that IL-6 is a product of these early conceptuses and may be involved in early maternal responses to the presence of an embryo within the uterus.
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PMID:Expression of interleukin-6 in porcine, ovine, and bovine preimplantation conceptuses. 149 80

We recently reported that human recombinant interleukin-6 (hrIL-6) microinjected into the preoptic area (POA) of guinea pigs induced fever at high doses, suggesting that IL-6 may be another endogenous pyrogen. This study was undertaken to determine whether hrIL-6 affects the single-unit activity of thermosensitive and thermally insensitive neurons in hypothalamic tissue slices and whether indomethacin (Indo) or naloxone (Nal), a cyclooxygenase inhibitor and a mu-opioid receptor antagonist, respectively, influences the effects of hrIL-6 on those neurons. hrIL-6 (2 x 10(3)-8 x 10(3) U/ml) depressed the activity in 50 (83%) of 60 warm-sensitive (W) neurons and excited all 4 cold-sensitive (C) neurons found. It had no effect, however, on 14 (48%) of 29 thermally insensitive (I) neurons, albeit 7 and 8 I neurons decreased and increased their firing rates, respectively. Indo (0.05-1 mg/ml) blocked the effect of hrIL-6 on 22 of 24 W neurons and 2 C neurons tested. Nal(0.1-1 mg/ml) blocked or reduced the effect of hrIL-6 on 21 of 25 W neurons and 1 C neuron recorded. These drugs induced no neuronal response per se. Nal at 2-5 mg/ml, which increased the activity of four W neurons by itself, reversed their depressed response to hrIL-6. These results support the possibility that IL-6-induced fevers may be mediated through an effect on thermosensitive neurons in the POA and that opioids and prostaglandin E may both be involved in this process.
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PMID:Hypothalamic neuronal responses to interleukin-6 in tissue slices: effects of indomethacin and naloxone. 150 50

To investigate the correlation between interleukin-6 and urothelial neoplasms, interleukin-6 activities in blood and urine samples of patients with bladder carcinoma were measured with a proliferation assay using an interleukin-6 dependent murine hybridoma clone, MH60.BSF2. A total of 43 patients and 15 normal volunteers were entered into this study. All of the patients were examined preoperatively and 26 were reexamined more than 6 days postoperatively to eliminate the effect of surgical injury on interleukin-6 secretion. The interleukin-6 titers in urine and serum increased in accordance with the progression of the tumor stage, and tumor removal induced a remarkable decrease in the titer of urinary interleukin-6. Although the interleukin-6-producing site has not been elucidated yet, our study suggests that interleukin-6 activity in bladder carcinoma patients may reflect the immunoreaction against the tumor in local urothelium.
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PMID:Interleukin-6 activity in urine and serum in patients with bladder carcinoma. 151 27

The carboxyl(C)-terminus of human interleukin-6 (hIL-6) has a critical role in the expression of the biological activity of this cytokine. To define the structure-function relationships of this region, semi-random mutagenesis of the C-terminal Leu181-Arg182-Qln183-Met184 sequence of hIL-6 was performed. The mutants were produced in Escherichia coli, renatured, and purified. Alterations of the C-terminal 4 amino acids caused a significant reduction of the proliferative effect of the mutants on MH60.BSF2 and KT-3 cells, and also led to a drastic decrease in receptor binding affinity. These results suggest the importance of a positively charged residue at position 182 or 183 and an alpha-helix at position 181 for the biological activity of hIL-6.
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PMID:Effect of semi-random mutagenesis at the C-terminal 4 amino acids of human interleukin-6 on its biological activity. 152 Feb 99

An atypical case of familial mediterranean fever is presented in a 55 year old male with neither family antecedents nor ethnic determinants. The patient presented isolated articular involvement and positive response in the metaraminol provocation and colchicine suppression test. It was associated with monoclonal type IgG kappa gammopathy which evolved over one year until obtaining criteria, although asymptomatic, for myeloma. The increase of the monoclonal component and the infiltration of the bone medulla by plasmatic cells were considered as signs of progression inducing the initiation of treatment despite the lack of symptoms. Both entities are discussed and a mechanism justifying their association is proposed: interleukin-6 produced by macrophages in the inflammatory articular foci due to the deficiency of the C5a inhibitor existing in familial mediterranean fever, may act on a plasmatic cell clone in which receptors for IL-6 exist as a paracrine growth factor.
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PMID:[Familial Mediterranean fever and myeloma: an undescribed association]. 154 23

We have investigated the dissociation, internalization, and degradation of 125I-interleukin-6 (125I-IL-6) by primary rat hepatocytes. Temperature shift experiments following saturation binding of 125I-IL-6 to cell surface receptors in hepatocytes showed a rapid loss of surface-bound 125I-IL-6 (t1/2 = 15 min), concomitant with a rapid rise in internalized radiolabeled ligand. After reaching a maximum by 30 min at 37 degrees C, the level of internalized 125I-IL-6 decreased with time and appeared in the culture media in a non-trichloroacetic acid-precipitable (degraded) state. The addition of the lysosomotropic agent chloroquine inhibited this receptor-mediated degradation of IL-6 without affecting ligand internalization. Polyacrylamide gel electrophoresis analysis of internalized 125I-IL-6 confirms these results. Additionally, we show that the IL-6.IL-6 receptor complex is stable, and dissociation of these two molecular species occurs at a pH below 5.0. In contrast to published results, data presented in this study clearly indicate that IL-6 is rapidly internalized and degraded within hepatocytes by a receptor-mediated mechanism.
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PMID:Dynamics of interleukin-6 internalization and degradation in rat hepatocytes. 155 93

The effects of interleukin-5 and interleukin-6 on immunoglobulin production in rat salivary glands were investigated using an in vitro tissue culture system. Detectable levels of IgA, IgG and IgM were observed in the culture media of unstimulated tissues of rat salivary glands after 7 days in culture. Incubation of the tissues with recombinant murine IL-5 (50 U/ml) enhanced the levels of IgA (205% of the control) and IgG (136% of the control), but had no effect on the levels of IgM. Similarly, incubation with recombinant human IL-6 (50 U/ml) enhanced IgA (224% of the control) and IgG (149% of the control) production, but had no effect on IgM. A combination of both IL-5 and IL-6 had no additional effect on the enhanced IgA levels than that seen with IL-5 or IL-6 alone. These data demonstrate a potential regulatory function of lymphokines in glandular mucosal tissue that differs from that previously noted in experiments with cultured rat lacrimal glands or isolated cells derived from both mucosal and non-mucosal tissues.
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PMID:Regulatory role of interleukins 5 and 6 on immunoglobulin production in cultured rat salivary glands. 158 78

Interleukin-6 is a member of a class of hormone-like molecules termed cytokines. The actions of IL-6 are highly pleiotropic. In adults IL-6 functions as a major mediator of inflammatory responses as well as inducing the synthesis of acute phase proteins by the liver following infection or injury. Based on in vitro and in vivo studies IL-6 also has important functions in regulating the development of multiple lineages of hemopoietic cells. It may also be an inflammatory mediator in the central nervous system. Although IL-6 has been found in early mouse embryos, its function has not yet been determined. Its expression by placental trophoblasts and maternal decidua suggests that it has some role in fetal-maternal interactions. Finally, the response of fetal hemopoietic progenitor cells to IL-6 suggests that IL-6 may have a broader action on the expansion and maturation of fetal precursors. New approaches such as those involving the disruption of the IL-6 gene in mice will be needed for a more complete understanding of IL-6's role in embryonic development.
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PMID:The role of interleukin-6 in development. 160 Nov 70

Biosensor technology employing surface plasmon resonance (SPR) detection provides a highly-sensitive (sub ng), non-extrinsic labelling approach for monitoring protein interactions in real-time. We have used this approach to map the binding sites on human interleukin-6 (hIL-6) for a series of anti-hIL-6 monoclonal antibodies (mAbs). Epitopes were localised by monitoring the ability of ten synthetic peptides, spanning the sequence of hIL-6, to inhibit the binding of anti-hIL-6 mAbs to immobilised hIL-6. Peptide P8 (Pro139-Gln153) inhibited binding of anti-IL-6-mAbs 1, 2 and 7. To increase the sensitivity of detection of antibody-synthetic peptide interactions, a procedure was developed for immobilising the synthetic peptides directly to the sensor surface of the SPR instrument. From this study, association equilibrium constants of 2.1 x 10(6)M-1 and 3.6 x 10(4)M-1 were calculated for the mAb7-immobilised P8 and mAb7-free P8 interactions, respectively.
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PMID:Binding of anti-human-interleukin-6 monoclonal antibodies to synthetic peptides of human interleukin-6 studied using surface plasmon resonance. 162 66


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