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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines play an essential role in normal and malignant B-cell proliferation and isotype-switching. Therefore we determined serum levels of different B-cell activating cytokines including IFN gamma, IL-4 and IL-10, IgG subclasses, further immunoglobulins and the soluble B-cell activation marker sCD23 in 68 patients with recently diagnosed and previously untreated IgG myelomas in comparison with age- and sex-matched healthy controls. Our results demonstrated that 16% of the myeloma patients had elevated IL-10 levels up to 1000 pg/ml and 8% showed increased IFN gamma serum concentrations. By contrast, only 7% of the controls showed detectable IL-10 levels and 3% had measurable IFN gamma levels. While in men 67% of the paraproteins were of the kappa light chain type, we found an equal occurrence of kappa and lambda light chains in women. In addition, the distribution of IgG subclasses differed in men and women. In comparison with the controls, no alteration of sCD23 was detected in myeloma patients. We found an apparent correlation of elevated IL-10 levels and the IgG1 subclass.
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PMID:[Cytokines, immunoglobulins, and IgG subclasses in patients with IgG plasmacytomas]. 792 79

The authors review contemporary findings on the role of different components of the cytokine network from the aspect of development, prognosis and treatment of multiple myeloma. Greatest attention was devoted to the main growth factor of myeloma elements IL-6, but also to the real or so far sparsely elucidated role of other cytokines (IL-1, IL-2, GM-CSF, G-CSF, IL-3, IL-4, IL-5, IL-10, TNF, interferon alpha and gamma) under conditions in vitro and in vivo. For completeness sake the authors did not omit the problem of the soluble receptor of IL-2 and the role of TNF, TNF beta and in particular IL-1 beta in the pathogenesis of osteolytic lesions and the potential therapeutic role of antibodies against IL-6 (anti IL-6 mab) and interferon alpha and gamma.
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PMID:[The cytokine network in multiple myeloma]. 794 39

Follicular dendritic cells (FDC) are specialized cells residing primarily within lymphoid follicles. They bind immunocomplexes and play an important role in the presentation of antigen to follicular B cells. Isolation of FDC for in vitro studies, however, is difficult because they constitute only about 1% of the cells in lymphoid tissue and form tight clusters entrapping lymphocytes within their dendritic processes. The monoclonal antibody (mAb) Ki-M4, which is highly restricted in its binding to FDC, is used to identify these cells. In order to establish a new immortalized cell line with features of FDC, we applied a modified procedure to isolate and enrich FDC from human tonsils and fused them with the myeloma cell line SP2/0-Ag14. The new hybrid cell line, designated FDC-H1, is of both mouse lymphoid and human FDC origin. FDC-H1 was found to have unlimited growth potential and to consistently express the Ki-M4 antigen and other surface antigens of human FDC. Semiquantitative reverse-transcribed polymerase chain reaction (RT-PCR) of enriched FDC and FDC-H1 revealed the same highly restricted cytokine/mRNA profile for both, with detectable levels of interleukin (IL)-1 alpha and surface CD23 and a lack of mRNA for IL-1 beta, IL-2, IL-3, IL-4, IL-7, IL-9, IL-10, interferon-gamma, tumor necrosis factor-alpha, transforming growth factor-beta and granulocyte/macrophage-colony-stimulating factor. Additionally a weak but constant IL-6 mRNA expression was found in the cell line FDC-H1 by RT-PCR. In situ hybridization experiments in tonsils revealed IL-6 transcripts in cells with a staining pattern characteristic of a dendritic cell only in a few germinal centers. To our knowledge, FDC-H1 is the first cell line that constantly expresses surface antigens and a cytokine profile characteristic of FDC. It is, therefore, well suited for studying the biology of FDC and the functional relationship between FDC and normal or neoplastic lymphatic cells.
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PMID:An immortalized cell line with features of human follicular dendritic cells. Antigen and cytokine expression analysis. 795 61

Immunoglobulin (Ig) E is the principal Ig involved in immediate hypersensitivities and chronic allergic diseases such as asthma. Helminths are the most potent infectious agents known for their capacity to stimulate IgE production during the course of infection. In rats, the nematode Trichinella spiralis typically elicits a strong parasite-specific IgE response during infection, and this IgE antibody has been shown to be protective against the parasite in passive transfer experiments. The study reported here analyzed the fate of 125I-labeled myeloma IgE (1R162) in normal and T. spiralis-infected rats after intravenous injection. T. spiralis infection induced a capacity for specific binding to the gut wall of 125I-IgE rather than 125I-IgG1, as well as the transport of IgE, but not IgG1, into the gut lumen. Peak intestinal uptake and transport of 125I-IgE occurred during the first and second weeks after injection but was not elevated in the fourth week, that is, after intestinal adult worms had been expelled. Neither 125I-IgE uptake in the gut wall nor transport to the lumen could be ascribed to tissue damage or vascular leakage. Luminal transport occurred in the small intestine and not the liver, which only transports low molecular weight degraded 125I-IgE. Calculations based on the amount of intact IgE in the lumen suggest that, in a 24-h period, up to 20% of injected 125I-IgE can be transported to the gut lumen during the peak transport period, between 6 and 14 d after infection. The intestinal IgE binding and transport response can be adoptively transferred with T. spiralis immune CD4+ OX22- (CD45RC-) lymphocytes, which are protective, but not the nonprotective sister population CD4+ OX22+ (CD45RC+) of lymphocytes isolated simultaneously from thoracic duct lymph of infected rats. The intravenous infusion of recombinant rat interleukin 4 also elicited significant intestinal uptake of 125I-IgE. We also present evidence for the presence of CD23 on rat intraepithelial lymphocytes. These data provide evidence for a novel, inducible, intestine-specific IgE uptake and transport mechanism.
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PMID:Evidence for an interleukin 4-inducible immunoglobulin E uptake and transport mechanism in the intestine. 796 61

Expression of mRNA for eight cytokines was analyzed in an in vitro response-proliferation and Ig-secretion--of normal human B lymphocytes. This was made possible by the use of murine thymoma cells as helper cells in conjunction with human T cell supernatant, and the design of human DNA sequence-specific primers for RT-polymerase chain reaction. mRNAs for interleukin (IL)2 and IL-4, but also for IL-1 alpha and IL-1 beta remained undetectable during the whole culture period in highly purified B cells prepared by a three-step purification protocol. However, tumor necrosis factor alpha and IL-6 mRNAs peaked during days 1-3 after culture start and became undetectable after 5-6 d, shortly before bulk B cell proliferation started to decline. In contrast, transforming growth factor beta 1 mRNA, after a progressive increase during the first few days, and IL-10 mRNA, after a peak on days 1-3, remained detectable in immunoglobulin (Ig)-secreting cultures throughout the observation period of 22 d. Clonal analysis on 8-d cultures that had been seeded with single B cells by autocloning with the cell sorter, revealed that 85% of 77 B cell clones studied, expressed TGF-beta 1 mRNA, and only 19% IL-10 mRNA. These findings show a differentiation stage-related cytokine program during a B cell response, whereby (a) B cells can become activated without IL-1 alpha or IL-1 beta expression; (b) mRNA for positive (IL-10) and negative (TGF-beta 1) autoregulatory factors coexists in cell populations during the later phase of the response, although not necessarily in all B cell clones; and (c) normal Ig-secreting cells cease IL-6 expression in contrast to their malignant counterparts, myeloma cells.
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PMID:Cytokine mRNA expression during an in vitro response of human B lymphocytes: kinetics of B cell tumor necrosis factor alpha, interleukin (IL)6, IL-10, and transforming growth factor beta 1 mRNAs. 810 60

The transgenic (TG) mouse strain 207-4, carries mu a + kappa transgenes ligated to the anti-phosphocholine (PC) VH1 and V kappa 24 V region genes from the MOPC-167 myeloma. Although B cells from mice carrying these transgenes respond both in vivo and in vitro to thymus-dependent Ags, they failed to proliferate in response to soluble goat anti-mu Ab or other soluble anti-Ig reagents. On the other hand, B cells from the Sp6 mu kappa anti-trinitrophenyl TG mouse line proliferated normally after stimulation with soluble anti-mu. However, the 207-4 anti-PC transgene positive (TG+) splenic B cells proliferated when stimulated with anti-mu, anti-idiotype, anti-allotype, or PC-conjugated to Sepharose beads. TG+ B cells were also induced to proliferate when stimulated with anti-Lyb-2; thus, their defect may be restricted to signaling through sigM. The lack of response to soluble anti-mu could not be reversed by addition of IL-4, by removal of T cells, by addition of anti-FcR Ab, or by stimulation with F(ab')2 anti-mu. Thus, the failure to proliferate was not caused by active T cell suppression or FcR-mediated inhibition. In mixed cultures of TG+ and transgene negative (TG-) spleen cells, the TG- cells were able to proliferate normally to soluble anti-mu, indicating that suppressive factors were not involved in the unresponsiveness of the TG+ anti-PC-specific B cells. These studies suggest that B cells in the 207-4 anti-PC TG mice exhibit a defect in activation through their sIgM receptors, and this unresponsiveness may reflect a form of Ag-induced tolerance.
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PMID:B cells from M167 mu kappa transgenic mice fail to proliferate after stimulation with soluble anti-Ig antibodies. A model for antigen-induced B cell anergy. 817 9

Studies of interleukin function often require large quantities of these highly expensive substances. The available interleukins are generally recombinant proteins produced in bacteria or yeast and, less commonly, interleukins produced by mammalian cells, which provide appropriate glycosylation and other post-translational modifications. Due to differences in biosynthesis, difficulties in production and purification the quality of the interleukin preparations may vary. We have taken advantage of the recently developed constitutively interleukin-secreting mouse myeloma cell lines and the dialysis tubing culture technique, which permit cells to be grown at high densities, in order to establish a method for the production of large amounts of recombinant murine IL-2 and IL-4. We show that these interleukins can be produced at low cost and in concentrations 20-30-fold higher than in conventional culture flasks. A single dialysis tubing culture will produce more than 10(6) U of interleukin which may be compared with the available commercial preparations containing between 10- and a 100-fold less per vial. The IL-2 and IL-4 produced in this manner are biologically active molecules as demonstrated by the strong proliferative response of clonal T cells and the isotype-switching effect in LPS-stimulated splenic B cell cultures. The dialysis tubing culture technique is a simple and highly cost-effective means of generating large quantities of biologically active interleukins and is especially suitable for research laboratories interested in functional studies of these proteins.
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PMID:Production of large amounts of recombinant interleukins by cDNA transfected mouse myeloma cells cultured in dialysis tubing. 828 89

Cytokines play a key-role in the immune response. The best known of them is interleukin-2 and its specific receptors. Monoclonal antibodies directed against the interleukin-2 receptor have initially enabled this receptor to be characterized; then they served to confirm the major role played by this cytokine in immune responses, where it proved effective in many animal models such as allograft reaction, delayed hypersensitivity reaction and some experimental auto-immune diseases. These results have been confirmed in man, particularly in kidney transplantation (but also in bone marrow transplantation), and they encourage to develop new bioreagents (chimeral antibodies, "humanized" antibodies, fusion proteins). Some of these reagents are now undergoing evaluation in renal transplantation. The principles of these bioreagents, issued from molecular biology, can be applied to other cytokines involved in the immunopathological mechanisms of certain diseases such as, for example, IL-6 and its role in the development of myeloma. Data from immune intervention directed against other cytokines are, for the moment, preliminary, but many potential targets (IL-1, IL-4, TNF alpha, INF gamma) are emerging.
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PMID:[Anti-cytokines and anti-cytokine receptors]. 834 28

To study the effects of cytokines on human IgE antibody forming cells (AFCs), log phase U266 myeloma cells (3 x 10(3)/ml), which secrete immunoglobulin E (IgE), were cultured for 0-24 h with and without cytokine or with or without antibodies against various cytokines. The numbers of IgE AFCs were determined in ELISPOT assay. We found that interleukin-6 (IL-6) suppressed (to 95%) whereas anti-IL-6 increased (to 148%) the numbers of IgE AFCs and that both worked in a dose-dependent fashion. IL-4 and interferon-gamma (IFN-gamma) also suppressed IgE AFC responses in a dose-dependent fashion. However, antibodies to these cytokines had no effect. In contrast, IFN-alpha increased (to fourfold) the numbers of IgE AFCs in a dose-dependent fashion. The data are the first to show a suppressive effect of IL-6 on human IgE responses and may also suggest a role for IL-6 in the treatment of atopic disease.
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PMID:Suppression of human IgE antibody forming cell responses by IL-6. 836 May 95

Interleukin 6 (IL-6)/hybridoma growth factor (HGF) has been shown to be the requirement for growth of murine hybridomas in vivo or in vitro. In this paper, two kinds of conditioned media (CM) from the culture supernatants of a human fibroblast cell line CRL1506 and a cloned Epstein-Barr virus (EBV) transformed human lymphoblastoid cell line (LCL) N23 were found to have IL-6 activity by strongly promoting the growth, antibody secretion (increase of one- to three-fold), and cloning efficiencies of heterohybridomas secreting human monoclonal anti-hemorrhagic fever with renal syndrome virus antibodies and LCL. Since these CM contained no detectable IL-2, and IL-4 had no effects on the growth of the cell lines, IL-6 was considered to be the main active component of the CM responsible for promoting hybridoma growth. This effect was further confirmed by IL-6-dependent cell line 7TD1 bioassay (IL-6 activity in the CM ranging from 1,000 to 10,000 units/ml). Moreover, we successfully established four EBV-transformed lymphoblastoid cell lines at single-cell level by adding an equal volume of CRL1506-CM to 10% FCS-RPMI1640 in limiting dilution. Finally, it is worth noting that the sensitivity of the heterohybridomas to the two kinds of CM was not the same and was not consistent with that of their parental myeloma cell lines. Thus, it suggests that the CM might contain more than one factor, and the choice of proper conditioned media should be very useful for human monoclonal antibody production.
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PMID:The effects of hybridoma growth factor in conditioned media upon the growth, cloning, and antibody production of heterohybridoma cell lines. 843 56


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