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

A wide variety of cytokines have been demonstrated to affect B-cell function. However, it is unclear which of these mediators actually exert direct effects on the B cells themselves. In the present study, the direct role of interleukin (IL) 1, IL-2, Interferon-gamma, or Interferon-alpha in human B-cell activation, proliferation, or differentiation was examined and compared with the effects of a B-cell growth factor (BCGF) or a B-cell differentiation factor (BCDF). Highly purified human B lymphocytes were separated according to size into two nonoverlapping populations. The fraction of small B cells was incubated with IL-1, IL-2, Interferon-gamma, Interferon-alpha, BCGF, or BCDF, and cell size changes, RNA synthesis, DNA synthesis, or supernatant immunoglobulin (Ig) production were measured. Neither IL-1, IL-2, Interferon-alpha, Interferon-gamma, nor the BCGF induced substantial cell size changes, RNA synthesis, DNA synthesis, or Ig production by the small fraction of B lymphocytes; however, the BCDF could directly activate a proportion of resting B lymphocytes to secrete Ig. The fraction of large B cells was also incubated with these cytokines. While neither IL-1, Interferon-alpha, nor Interferon-gamma enhanced DNA synthesis or Ig production by the fraction of large B lymphocytes, DNA synthesis was augmented 23-fold by BCGF and IgG production was increased 7-fold by BCDF. Additionally, IL-2 slightly enhanced both proliferation and differentiation of large B cells but substantially less so than BCGF and BCDF; DNA synthesis was increased 4-fold, while Ig production in the presence of IL-2 was increased by approximately 50%. Thus, the most important lymphokines modulating the function of these two fractions of tonsillar lymphocytes were a BCGF and a BCDF.
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PMID:The direct effects of interleukin 1, interleukin 2, interferon-alpha, interferon-gamma, B-cell growth factor, and a B-cell differentiation factor on resting and activated human B cells. 242 21

Primary mouse hepatocytes were treated with the acute-phase mediators interleukin-1, interleukin-6, and glucocorticoids, singularly and in combination, in order to delineate the spectrum of proteins induced by the stimulatory factors. As found for rat and human liver cells, mouse hepatocytes responded to the cytokines by increasing production of acute-phase proteins, which in mice include haptoglobin, alpha 1-acid glycoprotein, complement C-3, serum amyloid A, and hemopexin. Serum amyloid A was unusual in that only the acidic peptide form responded to treatment with IL-1 and IL-6; the more basic form remained unchanged. In addition, an unidentified secretory protein was induced only by mixtures containing IL-6. The present study shows that a combination of IL-1, IL-6, and glucocorticoids is required for regulation of acute-phase plasma protein production in mouse liver cells.
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PMID:Interleukin-1 and interleukin-6 stimulate acute-phase protein production in primary mouse hepatocytes. 246 23

Interleukin-6 (IL-6) is a multifunctional cytokine that plays a role in regulation of hematopoiesis. Because IL-6 is coinduced with colony-stimulating factors (CSFs) by various cell types in response to stimulation with IL-1, we investigated whether IL-6 is involved in the IL-1-induced production of CSF by human bone marrow (BM) cells in long-term culture or human fibroblasts. We showed that IL-6 does not induce CSF production by these cells. Neither addition of exogenous IL-6 nor neutralization of endogenous production of IL-6 by an anti-IL-6 monoclonal antibody (MoAb) diminished the IL-1-induced colony-stimulating activity (CSA), indicating that IL-6 did not act synergistically with IL-1. Finally, IL-6 did not influence the kinetics of IL-1-induced CSA production by human fibroblasts. We conclude that IL-6, either alone or in combination with IL-1, does not induce CSF production by human BM stromal cells or fibroblasts.
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PMID:Interleukin-6 is not involved in the interleukin-1-induced production of colony-stimulating factors by human bone marrow stromal cells and fibroblasts. 247 24

Human C-reactive protein (CRP) is the major acute phase reactant during acute inflammation. The human CRP promoter is expressed in an inducible and cell-specific manner when linked to the bacterial CAT gene and transfected into human hepatoma cell cultures. In this paper we analyze the effect of several recombinant cytokines or CRP promoter inducibility in human Hep3B cells. When cytokines are tested singly the major inducer of CRP-CAT fusions is interleukin-6 (IL-6). Maximal CAT gene expression, however, is only achieved when both interleukin-1 beta (IL-1 beta) and IL-6 are present. The response to the two cytokines is cooperative. Cooperativity is maintained when the CRP promoter is linked to a different coding region, that of the bacterial neomycin phosphotransferase II gene. With a series of 5' and 3' deletions we show the existence of two distinct and independent regions responsive to IL-6 and located upstream to the TATA box. The IL-1 effect is exerted at the level of downstream sequences that are probably important for optimal mRNA translatability or nuclear-cytoplasmic transport. Inducibility is not influenced by the activation of protein kinases C or A and does not require new protein synthesis.
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PMID:Dual control of C-reactive protein gene expression by interleukin-1 and interleukin-6. 255 73

Stromal cells are believed to regulate lympho-hematopoiesis through direct cell-cell interactions and the release of growth factors. Many questions remain, however, about their lineage derivation and functional heterogeneity. We previously prepared a panel of stromal cell lines from murine spleen and bone marrow and characterized them based on their ability to support lymphocyte growth in long-term cultures. These cells are now compared with respect to their expression of various immunoglobulin superfamily and cytokine genes by Northern blot analysis. These results indicate that although stromal cells appear to be mesodermal in origin, they are not closely related developmentally to the hematopoietic progenitor cells they support. The potential production of at least six cytokines was demonstrated. All clones constitutively expressed mRNA for macrophage colony stimulating factor, interleukin-6, transforming growth factor beta and neuroleukin. The most potent lymphocyte supporting clones also made interleukin 7 constitutively. Previous findings had suggested that these clones responded to exogenous stimuli and this has now been demonstrated in terms of induced expression of IL-6 and G/M-CSF mRNA. Interleukin 6 mRNA levels were markedly upregulated by exposure of cells to LPS, TNF, IL-1, IL-6, IL-7, and EGF. G/M-CSF mRNA levels were "superinduced" by the combination of LPS and cycloheximide, a protein synthesis inhibitor. These responses are similar to ones documented by investigators working with endothelial cells and fibroblasts. Together, these data suggest that stromal cells are a multifunctional component of the lymphopoietic microenvironment and may be active participants in a complex, cytokine-mediated regulatory network.
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PMID:Characterization of murine bone marrow and spleen-derived stromal cells: analysis of leukocyte marker and growth factor mRNA transcript levels. 256 60

After in vivo immunization with antigen, B cells appear in the peripheral blood which can be induced in vitro by nonspecific factors found in mixed lymphocyte culture supernatants (MLC-SN) to differentiate and secrete antibody specific for the immunizing antigen. In order to further delineate the nature of the factors involved in the differentiation of these in vivo-activated B cells, various helper factors, including interleukin 1 and interleukin 2 (IL-1 and IL-2), B-cell growth factor (BCGF), and B-cell differentiation factor (BCDF) were added separately and in combination to cultures of these preactivated B cells. T-cell-depleted fractions of peripheral blood mononuclear cells were obtained from normal individuals immunized in vivo with keyhole limpet hemocyanin. MLC-SN alone, without the addition of antigen, selectively triggered an antibody response specific for the antigen used to immunize in vivo in the absence of a polyclonal B-cell response. In order to obtain responses equal to those seen with MLC-SN, a combination of BCGF, IL-2, and BCDF was required, although any two factors partially reconstituted the response. Exogenous IL-1 had the least effect but was suppressive in the presence of optimal concentrations of monocytes. Thus, for maximal in vitro differentiation of in vivo-preactivated B cells, a combination of at least three helper factors is required and acts in a synergistic manner to induce antigen-specific antibody responses.
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PMID:Synergy of helper factors in the differentiation of in vivo-preactivated antigen-specific human B cells. 257 96

The formation of CD8+ killer cells from nonlytic thymocyte precursors is mediated by interleukin 2 and a cytokine termed CTL differentiation factor (CDF). While several reports have focused on the effects of recombinant molecules on the development of CTL, the natural protein responsible for CTL development that is produced by normal leukocytes has not been conclusively identified. A 24 kD native protein with CDF activity was enriched from leukocyte conditioned medium and neutralizing antibodies were produced. Utilizing immunoaffinity chromatography and reverse phase chromatography, we purified this CDF to homogeneity. All 21 amino acid residues at the NH2-terminus of CDF were found to be identical to that of IL-6. Natural CDF and IL-6 share many of the same biological properties, including costimulation of thymocyte proliferation with IL-1. Antibodies against CDF or IL-6 can block the activity of either cytokine, and anti-CDF blocks the activity of bulk leukocyte conditioned medium. These results indicate that IL-6 is the principal CTL differentiation factor produced by stimulated human leukocytes.
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PMID:Interleukin 6 is the principal cytolytic T lymphocyte differentiation factor for thymocytes in human leukocyte conditioned medium. 261 Aug 54

Early 4-hydroxyperoxycyclophosphamide (4-HC) resistant hematopoietic progenitor cells (pre-colony-forming units, pre-CFU) were evaluated by a two-step liquid culture system, (earlier progenitors), pre-CFU, as well as by the conventional semi-solid mixed colony assay (later progenitors) for their growth response to interleukin-6 (IL-6), interleukin-3 (IL-3), and a combination of both factors. The effect of the IL-6/IL-3 combination was compared to that of IL-1/IL-3. IL-3 alone proved less effective in supporting earlier pre-CFU cells than later progenitor cells. In a previous work IL-6 promoted the growth of early multipotential progenitor cells circulating in hairy cell leukemia (HCL) patients. IL-6 alone did not stimulate growth of either early or later normal progenitor cells. However, a significant synergistic effect was obtained when IL-6 and IL-3 were added together (p less than 0.05). IL-6/IL-3 synergism was more potent than IL-1/IL-3 in promoting growth of colonies. The previously described synergistic effect of IL-1/IL-3 seems to be independent of IL-6. Thus, our results suggest that the multi-functional cytokine IL-6, may be of use in shortening the engraftment time in bone marrow transplantation.
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PMID:Interferon beta 2/interleukin-6 and interleukin-3 synergize in stimulating proliferation of human early hematopoietic progenitor cells. 263 33

The central feature of hemopoiesis is life-long, stable cell renewal. This process is supported by hemopoietic stem cells which, in the steady state, appear to be dormant in cell cycling. The entry into cell cycle of the dormant stem cells may be promoted by such factors as interleukin-1, interleukin-6 (IL-6), and granulocyte colony-stimulating factor (G-CSF). Once the stem cells leave G0 and begin proliferation, the subsequent process is characterized by continued proliferation and differentiation. While several models of stem cell differentiation have been proposed, micromanipulation studies of individual progenitors suggest that the commitment of multipotential progenitors to single lineages is a random (stochastic) process. The proliferation of early hemopoietic progenitors requires the presence of interleukin-3 (IL-3), and the intermediate process appears to be supported by granulocyte/macrophage colony-stimulating factor (GM-CSF). Once the progenitors are committed to individual lineages, the subsequent maturation process appears to be supported by late-acting, lineage-specific factors such as erythropoietin and G-CSF. Synthesis of a hemopoietic factor may take place in different cell types and is regulated by multiple factors. The physiological regulator of erythropoiesis is erythropoietin, which, by a feedback mechanism, provides fine control of erythrocyte production. Feedback mechanisms for leukocyte production have not been identified. It is possible that there is no feedback regulator of leukopoiesis. In this model, leukocyte production in the steady state is maintained at a genetically determined level. When an infection occurs, the bacterial lipopolysaccharides may augment the production of interleukin 1 alpha and beta, tumor necrosis factor, macrophage colony-stimulating factor, etc.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemopoietic stem cells: stochastic differentiation and humoral control of proliferation. 264 80

An assay system was developed to measure feline hybridoma growth factor (HGF)/interleukin-6 (IL-6) activity in biological samples containing many kinds of cytokines by using the proliferation of the newly established mouse-rat hybridoma clone, B3B1. The proliferative response of this B3B1 clone was IL-6-specific, and could not be promoted by other cytokines including IL-1, IL-2, IL-3, and granulocyte-colony-stimulating factor (G-CSF). The anti-human B-cell stimulatory factor 2 (BSF-2)/IL-6 antiserum did not neutralize feline HGF/IL-6 activity in conditioned media prepared from feline con A-stimulated splenocytes and unstimulated alveolar macrophages, indicating antigenic differences between species. Feline HGF/IL-6 was eluted into the fractions corresponding to a molecular weight of 30,000-40,000 in gel filtration, and into the fractions at a salt concentration of 0.2-0.3 M NaCl in anion exchange chromatography. The physicochemical properties of feline HGF/IL-6 were slightly different from those of murine and human IL-6.
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PMID:Feline hybridoma growth factor/interleukin-6 activity. 268 91


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