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

We investigated the regulation of IL6 biological activity, de novo synthesis, and mRNA levels in adult vascular endothelial cells (EC) by bacterial endotoxin or inflammatory cytokines. Cells incubated without stimulus released scant IL6 activity. IFN gamma, IL2, or PDGF did not augment IL6 release from EC. LPS, lipid A, and TNF increased IL6 release modestly (5 to 20-fold), while recombinant IL1s (rIL1s) stimulated this process 100 to 400-fold. Differential release of IL6 from EC treated with LPS or rIL1 continued for at least 144 hr. Exposure to LPS or rIL1 caused EC to synthesize IL6 de novo. EC secreted the newly synthesized IL6 into the supernatant, rather than retaining it within or bound to cells. EC accumulated IL6 mRNA after 3 hr of exposure to rIL1. However, we could only detect IL6 message in cells incubated with LPS under "superinduction" conditions with cycloheximide, consistent with lower levels of IL6 biological activity in response to LPS compared to IL1 stimulation. We propose that local production of IL6 by vascular EC, which comprise the barrier between tissues and the blood, may influence regional immune and inflammatory responses.
Cell Immunol 1989 Sep
PMID:Adult human vascular endothelial cells express the IL6 gene differentially in response to LPS or IL1. 278 20

Rat peritoneal exudate cells produce two interleukin 6 (IL6) messenger RNA species, a major 1200 nucleotide and a 5-fold less abundant, 2400-nucleotide species. A cDNA clone representing the major species was isolated, and sequenced. The 1055-base pair insert covered the 3'-nontranslated region, the 211 triplet coding region and most of the 5'-nontranslated region. The derived rat IL6 amino acid sequence was 93 and 58% identical, respectively, with mature murine and human IL6. Rat IL6 lacks N-glycosylation sites but contains a fifth cysteinyl residue in addition to the 4 residues shared in conserved positions with murine and human IL6. Stable murine L cell and human HeLa-derived cell lines were established by cotransfection with rat IL6 cDNA and a selectable neomycin resistance marker. These lines secrete 9-fold increased amounts of functional IL6 over their respective parental cells. A stable rat macrophage-derived cell line, RM-SV1, was established by transformation with simian virus 40. IL6 and Il1 mRNA levels are inducible 20- and 3.5-fold, respectively, in this line by treatment with lipopolysaccharide with kinetics characteristic of macrophages. A set of three overlapping genomic DNA clones was isolated and a 10-kilobase DNA segment was sequenced containing the rat IL6 gene plus 2.9 kilobases of 5'-flanking and 1.3 kilobases of 3'-flanking sequences. The two transcription start sites used in RM-SV1 cells were mapped within 5 base pairs of each other. The exon/intron boundaries are conserved with the murine and human IL6 genes. The two IL6 mRNA species are generated by alternative polyadenylation at sites separated by a distance of 1.2 kilobases. The intervening region contains a repetitive element 72-80% identical with the rat and murine consensus L1 family sequences.
J Biol Chem 1989 Sep 25
PMID:Structure of the rat interleukin 6 gene and its expression in macrophage-derived cells. 278 17

In order to assess the effect of interleukin-6 on the hypothalamo-pituitary-adrenal axis, we administered recombinant human interleukin-6 to conscious, freely-moving rats. The intravenous injection of interleukin-6 significantly increased the plasma level of adrenocorticotropic hormone 30 min after the injection in a dose-related manner. Immunoneutralization of corticotropin-releasing hormone blocked the stimulatory effects of interleukin-6 on adrenocorticotropic hormone secretion. These observations suggest that interleukin-6 stimulates the secretion of adrenocorticotropic hormone through the corticotropin-releasing hormone and is possibly involved in the interaction between the neuroendocrine and immune system.
Biochem Biophys Res Commun 1988 Sep 30
PMID:Interleukin-6 stimulates the secretion of adrenocorticotropic hormone in conscious, freely-moving rats. 284 68

We have previously described YA2, a human T-cell clone that secretes B-cell differentiation factor (BCDF) but not B-cell growth factor (BCGF). The BCDFs secreted by YA2 and HTLV-I-transformed YA2 (TYA2) were functionally similar in their ability to stimulate Ig secretion by Staphylococcus aureus Cowan strain I-activated B cells and IgM secretion by SKW6.4 cells. In addition, they were biochemically similar with a MW of 30 kDa by high-performance liquid chromatography (HPLC) sieving, and a pI of 6.0-6.8 by isoelectric focusing. The BCDF activity was not blocked by antibodies to interleukin 2 and BCGF. BCDF was purified from TYA2 supernatant by sequential media protein immunoadsorption, flat bed isoelectric focusing, HPLC TSK 2000 sieving, and repeated immunoadsorption and was then iodinated. The iodinated material had functional BCDF activity and migrated to a single band at MW 30 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and at pI of 6.8 by polyacrylamide gel isoelectric focusing. 125I-BCDF purified in this manner bound specifically to a BCDF-responsive cell line and not to phytohemagglutinin-activated T cells. 125I binding to the BCDF-responsive cell line was competitively inhibitable by the addition of cold BCDF. Thus we have purified and characterized a factor with BCDF activity and demonstrated that this factor binds specifically to a BCDF-responsive cell line.
Cell Immunol 1987 Sep
PMID:Functional and biochemical characterization of B-cell differentiation factor (BCDF) produced by an HTLV-I-transformed human T-cell clone and demonstration of specific binding of the factor to a BCDF responsive cell line. 288 97

Interferon (IFN)-alpha and IFN-beta ("type I" IFNs), but not IFN-gamma reduced phytohemagglutinin- or pokeweed mitogen (PWM)-induced proliferation in cultures of human mononuclear leukocytes. Proliferation induced by specific antigens (tuberculin PPD or tetanus toxoid) or by exogenous interleukin 2 (IL-2) was strongly inhibited by type I IFNs and, to a lesser extent, by IFN-gamma as well. Inhibition of proliferation in mitogen-stimulated cultures was not due to a reduced production of IL-2 or to an inhibition of IL-2 receptor expression. Type I IFNs inhibited immunoglobulin (Ig) production in PWM-stimulated unseparated mononuclear cells, whereas IFN-gamma enhanced Ig production in such cultures. In cultures of purified B cells type I IFNs caused a stimulation of Ig production and this B-cell differentiation factor (BCDF)-like activity of IFNs was synergistically enhanced in the presence of IL-2. IFN-gamma produced less BCDF-like activity than type I IFNs. These results show that in some instances type I IFNs can be more potent in affecting functions of cells of the immune system than IFN-gamma.
Cell Immunol 1986 Sep
PMID:Modulation of lymphocyte proliferation and immunoglobulin synthesis by interferon-gamma and "type I" interferons. 309 92

CD28 is an Ag of 44-kDa Mr that is expressed on the membrane of the majority of human T cells and that is recognized by mAb 9.3. The functional effects of mAb 9.3 on peripheral blood T cells were studied. mAb 9.3 was not mitogenic, unless it was combined with PMA. When CD28 was cross-linked after binding of mAb 9.3 to the T cell by immobilized or soluble anti-mouse IgG, T cells proliferated in response to rIL-2, provided that monocytes were also present. The additional signal required for IL-2 responsiveness after cross-linking of CD28 could also be delivered in cultures of purified T cells by a cellfree monocyte culture supernatant. Expression of IL-2R on about 10% of the T cells was demonstrated by staining with an anti-IL-2R mAb, and was found to be largely restricted to CD4+ cells. The active compound responsible for the helper signal in the monocyte culture supernatant was identified as IL-6 because purified IL-6 (but not IL-1 beta) had similar activity and because an antiserum to IL-6 (but not an antiserum to IL-1 beta) neutralized the activity of the monocyte supernatant and blocked T cell proliferation. An anti-IL-2R antibody also completely inhibited T cell proliferation induced by the combination of mAb 9.3, IL-2, and IL-6. Our results provide evidence that cross-linking of CD28 induces functional IL-2R and that this activity is dependent on a helper signal provided by monocytes, more specifically IL-6. Moreover, our results indicate that IL-6 (previously called B cell stimulatory factor-2) is active on T cells. If a natural ligand for CD28 can be identified, the mechanism of induction of IL-2 responsiveness described here might explain how T cells become nonspecifically involved in an ongoing cellular immune reaction.
J Immunol 1988 Sep 01
PMID:Cooperation between an anti-T cell (anti-CD28) monoclonal antibody and monocyte-produced IL-6 in the induction of T cell responsiveness to IL-2. 326 51

Murine interleukin-HP1 (HP1) was originally identified as a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas and plasmacytomas. This growth factor was recently shown to stimulate both normal B-cell differentiation and T-cell growth factor activity. We have determined the complete amino acid sequence of HP1 on 40 micrograms (approximately 2 nmol) protein using a combination of sensitive microbore column (1.0 and 2.1 mm internal diameter) HPLC, peptide mapping and automated amino acid microsequence analysis. Ion-pairing chromatography was employed to isolate hydrophilic peptides which were not retained on conventional reversed-phase HPLC systems. The molecule consists of 187 amino acid residues with a calculated molecular mass of 21710 Da. Although there is virtually no similarity between the NH2-terminal region of HP1 and its human biological counterpart (26-kDa protein/interferon-beta 2 = B-cell stimulatory factor-2/interleukin-6), these studies demonstrate extensive amino acid similarity in the middle and COOH-terminal regions of these molecules suggesting that HP1 is the murine homologue of human interleukin-6.
Eur J Biochem 1988 Sep 01
PMID:Murine hybridoma/plasmacytoma growth factor. Complete amino-acid sequence and relation to human interleukin-6. 326 59

We studied the ability of four clinically relevant particle species to stimulate human peripheral blood monocytes to release bone-resorbing agents, including interleukin-1 (both interleukin-1 alpha and interleukin-1 beta), interleukin-6, and prostaglandin E2. The species studied were titanium-6% aluminum-4% vanadium (TiAlV), commercially pure titanium, fabricated ultrahigh molecular weight polyethylene, and polyethylene retrieved from interfacial membranes of failed uncemented total hip arthroplasties. For all species, the mean size was less than 1 micron. Human peripheral blood monocytes were challenged with these particles in a uniform manner on the basis of surface area. Phorbol 12-myristate acetate, zymosan, and nonphagocytosable titanium particles served as controls. Stimulation of human monocytes is a function of the composition and concentration of particles. In this study, TiAlV particles appeared to be the most competent to elicit the synthesis and release of inflammatory mediators. Particles of commercially pure titanium and of fabricated ultrahigh molecular weight polyethylene also could induce the release of various cellular mediators, albeit at a lower level, whereas the particles of polyethylene retrieved from interfacial membranes were less stimulatory in these short-term in vitro experiments.
J Orthop Res 1995 Sep
PMID:Human monocyte response to particulate biomaterials generated in vivo and in vitro. 747 59

In a group of 111 patients with multiple myeloma (MM) comprising a group of 34 patients examined when the diagnosis was established and a group of 77 patients evaluated in different stages of the disease, the author examined the relationship between the interleukin-6 serum level (IL-6), assessed by the method of enzyme immunoanalysis and selected laboratory indicators of the disease. Elevated IL-6 values were recorded in 38% of the patients. In neither of the groups significant relations were found between IL-6 and calcium, urea, creatinine levels, the amount and type of monoclonal immunoglobulin, lacticode dehydrogenase, beta 2-microglobulin, ferritin, IL-2 and its soluble receptor in serum and the incidence of myeloma plasmocytes in bone marrow. In the second (but not in the first) group a significant relationship was recorded between IL-6 levels and the red cell sedimentation rate, the Hb value, the CRP level and serum albumin and the value of thymidinekinase in serum of patients with a value beyond the normal range. From the investigation ensues that examination of IL-6 serum levels in MM contributes so far mainly to improvement of the diagnosis and expedient classification of this disease in clinical practice.
Vnitr Lek 1995 Sep
PMID:[Serum interleukin-6 in multiple myeloma: I. Relation to selected laboratory indicators of disease]. 748 49

In a group of 111 subjects with multiple myeloma (MM) comprising a group of 34 patients examined when the diagnosis was established and a group of 77 patients examined in different stages of development of MM the authors evaluated the relationship between interleukin-6 (IL-6) serum levels and the clinical activity and the stage of the disease. In both groups a significant relationship was found between IL-6 and the clinical activity of MM; "stable" and "active" stages of the disease differed by the frequency of elevated values and the level of IL-6. In both groups the authors recorded rising levels and a rising rate of subjects with elevated IL-6 levels with advancing stages of the disease. When staging systems were used according to Durie-Salmon, the British Medical Research Council and according to Bataille the highest IL-6 values were recorded in the third stage of the disease, these values being significantly higher than in stages 1 and 2. In the group assembled at the time of assessment of the diagnosis of MM the described differences did not reach (with the exception of the evaluation according to Bataille) statistical significance. The classification of patients in stages 1-3 into sub-groups with regard to the activity of the disease ("stable" and "active") was associated with significantly different IL-6 levels. The investigation revealed that examination of IL-6 levels contributes at present rather to the understanding of the pathogenesis and biology of MM than to practical evaluation of the severity, activity and stage of the disease.
Vnitr Lek 1995 Sep
PMID:[Serum interleukin-6 in multiple myeloma. II. Relation to activity and stage of disease]. 748 50


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