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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma cells isolated from bone marrow (BM) aspirates of 15 patients with active multiple myeloma (MM) were cultured and analysed for in vitro proliferative response and Ig-synthesis upon stimulation with interleukin-3 (IL-3), interleukin-4 (IL-4) and interleukin-6 (IL-6). The proliferative response, determined as Ki-67 positivity in concentrated plasma cells, was increased by IL-6 (Stimulation Index, SI = 1.77 +/- 0.21 (M +/- SEM] but not by IL-3 or IL-4. This proliferation could be blocked by anti-IL-6. In vitro Ig-synthesis was stimulated by IL-4 (SI = 1.62 +/- 0.12 (M +/- SEM) P less than 0.05) but not by IL-6 or IL-3. This effect was not antagonized by anti-IL-6. An inverse correlation was found in this group of patients between the IL-6 induced stimulation of plasma cell proliferative activity and the IL-4 induced increase of Ig-synthesis (P = 0.027). These data indicate in MM that Ig-synthesis and the in vitro proliferative activity may be stimulated by different haematopoietic growth factors, which may reflect the involvement of different responding cells.
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PMID:In vitro Ig-synthesis and proliferative activity in multiple myeloma are stimulated by different growth factors. 177 80

Peripheral blood mononuclear cells from 8 normals and 8 patients with atopic dermatitis (AD) were cultured with recombinant interleukin-4 (IL-4) and the IgE and IgG subclass levels in the culture supernatants measured by radioimmunoassays. IL-4 induced IgE and IgG4 secretion by B cells from both normals and AD patients whereas it has no consistent effect on IgG1, IgG2 and IgG3 secretion. The IL-4 dose response was similar for IgE and IgG4 secretion by cells from both normals and AD patients. On the average, the patients' cells secreted more IgE and less IgG4 than the cells from normals, but because of a large variation, the differences were not significant. However, the ratio of IgG4:IgE secretion was significantly greater for normals than AD patients (mean +/- SEM 7.1 +/- 1.6:1 vs. 1.5 +/- 0.4:1; p less than 0.01). The data demonstrate that IL-4 induces IgE and IgG4 secretion by B cells from both normals and AD patients and suggest that the IL-4 induced switch from IgM to IgG4 or IgE secretion may proceed preferentially to IgE in AD patients as compared to normals.
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PMID:Interleukin-4 induced IgE and IgG4 secretion by B cells from atopic dermatitis patients. 193 71

Peripheral blood mononuclear cells (PBMCs) from healthy nonallergic donors were cultured with recombinant interleukin-4 (rIL-4), and the Ig of different isotypes was quantitated in the culture supernatants by radioimmunoassays. Recombinant IL-4 induced IgG4 and IgE secretion in a dose-dependent manner, whereas it had no consistent effect on the secretion of the other isotypes. In the absence of rIL-4, B cells in the PBMC preparations secreted less than 1 ng IgE/ml and a mean of 5 ng IgG4/ml. In the presence of the optimal dose of 100 U rIL-4/ml, PBMCs from five donors secreted a mean +/- SEM of 37 +/- 8 ng IgE/ml and 66 +/- 25 ng IgG4/ml. In kinetic studies, no IgG4 or IgE secretion was detected during the first 5 days of culture, and approximately 50% of the IgG4 and IgE secreted by day 15 was detected in supernatants on day 7. Cycloheximide, actinomycin-D, and mytomycin-C completely inhibited the rIL-4-induced IgG4 and IgE secretion, indicating that de novo protein, RNA, and DNA synthesis was required. As shown by Percoll buoyant density centrifugation, rIL-4 induced B cells in the high-density fraction to secrete IgG4 and IgE, whereas it inhibited spontaneous IgG4 secretion by low-density B cells. Interferon-gamma inhibited IL-4-induced IgG4 and IgE secretion. The data demonstrate that IL-4 induces small, dense, peripheral blood B cells to secrete not only IgE but also IgG4, which parallells the IL-4-induced IgE and IgG1 secretion by murine B cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-4 induces both IgG4 and IgE secretion by peripheral blood B cells. 212 56

This report presents results concerning the potential role of negative regulators in hematopoietic suppression observed in human immunodeficiency virus (HIV)-infected long-term cultures (LTC) of human bone marrow cells. Confluent stromal cell layers established from human bone marrow cells were exposed to HIV-1ADA, a monocytotropic strain of HIV-1. A progressive increase in the concentration of HIV-1 p24 antigen in cultures exposed to HIV-1ADA demonstrated that there was a productive infection. Cells from both noninfected and HIV-infected stromal cell layers produced factors that stimulated the proliferation of colony-forming units for granulocytes and macrophages (CFU-GM) from non-infected CD34+ cells. In contrast, when noninfected CD34+ cells were directly cocultured on intact stromal cell layers fewer CFU-GM and burst-forming units for erythroid cells (BFU-E) were detected in HIV-infected LTC than in noninfected LTC. One week after the addition of CD34+ cells, the number of CFU-GM in HIV-infected LTC in six of nine experiments was reduced compared to noninfected control LTC. In those six experiments, the number of CFU-GM was only 53 +/- 5% (SEM) of the number in noninfected LTC. The number of BFU-E in HIV-1-infected LTC was only 46 +/- 5% of the number in noninfected LTC (n = 5). There were fewer BFU-E in HIV-1-infected LTC, whether or not there was a reduced number of CFU-GM. Neutralizing antibody to tumor necrosis factor alpha (TNF-alpha) had no effect on the number of BFU-E in HIV-infected LTC. The number of BFU-E, however, was 2.1 +/- 0.2-fold greater (n = 3) in HIV-infected LTC incubated with neutralizing antibody to interferon-alpha. In HIV-infected LTC with decreased numbers of CFU-GM, the number of CFU-GM was approximately 2-fold greater after incubation of HIV-infected LTC with anti-interleukin-4 (IL-4). The effect of anti-TNF-alpha was variable, and anti-transforming growth factor-beta had no effect on the number of CFU-GM in HIV-infected LTC. After 2 weeks, the number of CFU-GM in HIV-infected LTC incubated with anti-IL-4 and anti-TNF-alpha was 2- to 4-fold greater than in untreated HIV-infected LTC. Antibody treatment did not promote an increase in the number of CFU-GM in noninfected LTC or in LTC in which CFU-GM numbers were not reduced after HIV infection.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Negative regulators may mediate some of the inhibitory effects of HIV-1 infected stromal cell layers on erythropoiesis and myelopoiesis in human bone marrow long term cultures. 754 Jun 43

Human lung dendritic cells (DC) are considerably more potent than alveolar macrophages (AM) in inducing allogeneic T-cell proliferation. Tumor necrosis factor (TNF) alpha and beta produced during alloreaction are likely to be major inflammatory cytokines involved. Their concentrations were therefore analyzed during the interaction of AM or DC with allogeneic T cells. TNF alpha and TNF beta levels were respectively three-fold and sevenfold higher in the presence of DC as compared with AM. Cytokines such as interleukin-4 (IL-4), interleukin-10 (IL-10), and transforming growth factor beta (TGF beta) were compared as to their ability to control DC-induced T-cell proliferation as well as TNF alpha or TNF beta production. IL-10 had the unique capacity of reducing both TNF alpha and TNF beta production by 60 +/- 5% (mean +/- SEM) and 63 +/- 12%, respectively, while inhibiting T-cell proliferation by only 32 +/- 23%. IL-4 and TGF beta increased the release of TNF beta by 275 +/- 22% and 95 +/- 32%, respectively, while that of TNF alpha was slightly decreased or unchanged. An additive effect of IL-10 to cyclosporine was found for all three parameters studied. Interaction between CD4 or CD8 with DC was affected similarly by IL-10. Part of this effect could be due to the downregulation of class I and class II major histocompatibility complex expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-10 decreases tumor necrosis factor alpha and beta in alloreactions induced by human lung dendritic cells and macrophages. 759 41

We investigated the effects of interleukin-4 (IL-4) on the survival of leukemic and normal B-cell progenitors cultured on bone marrow stroma. IL-4 (at 100 U/mL) was cytotoxic in 16 of 21 cases of B-lineage acute lymphoblastic leukemia, causing reductions in CD19+ cell numbers that ranged from 50% to greater than 99% (median 83.5%) of those in parallel cultures not exposed to the cytokine. All nine cases with the t(9;22)(q34;q11) or the t(4;11)(q21;q23), chromosomal features that are often associated with multidrug resistance and a fatal outcome, were susceptible to IL-4 toxicity. IL-4 cytotoxicity resulted from induction of programmed cell death (apoptosis); there was no evidence of cell killing mediated by T, natural killer, or stromal cells. IL-4 cytotoxicity extended to a proportion of normal B-cell progenitors. After 7 days of culture with IL-4 at 100 U/mL, fewer CD19+, CD34+ normal lymphoblasts (the most immature subset) survived: in five experiments the mean (+/- SEM) reduction in cell recoveries caused by IL-4 was 60.0% +/- 6.0%. By contrast, reductions in recovery of more differentiated bone marrow B cells (CD19+, CD34-, surface Ig+) were low (6.6% +/- 2.2%; P < .001 by t-test). Our findings indicate that IL-4 is cytotoxic for human B-cell precursors and support clinical testing of IL-4 in cases of high-risk lymphoblastic leukemia resistant to conventional therapy.
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PMID:Interleukin-4 induces programmed cell death (apoptosis) in cases of high-risk acute lymphoblastic leukemia. 814 40

Previously, Puri et al. (Puri, R. K., M. Ogata, P. Leland, G. M. Feldman, D. Fitzgerald, and I. Pastan. 1991. Cancer Res. 51:3011-3017) have demonstrated that murine sarcoma and colon adenocarcinoma cells express high affinity interleukin-4 receptors (IL-4R) which are internalized after binding to a chimeric ligand consisting of IL-4 and Pseudomonas exotoxin. In the present study, we have tested primary cultures of human renal cell carcinoma (RCC) cells, generated from tumor specimens obtained after nephrectomy, for the expression of IL-4R and their modulation by IL-4. By using iodinated IL-4 in a receptor binding assay, we observed that renal cell carcinoma cells expressed a single class of high affinity IL-4R ranging from 1,425 +/- 207 (mean +/- SEM) to 3,831 +/- 299 (mean +/- SEM) IL-4R molecules/cell with a Kd ranging from 112 +/- 11 pM to 283 +/- 71 pM. Northern blot analysis for IL-4R gene expression, performed with a cDNA probe to IL-4R, revealed that all RCC cells exhibited a single mRNA species of 4 kb. IL-4 downregulated the surface expression of IL-4R on one RCC tumor cell line. The function of IL-4R expression on RCC tumor cells was further determined by investigating the effect of IL-4 on tumor cell growth in vitro and comparing it with IL-4 effect on growth of normal fibroblast and endothelial cell lines. Tumor cell growth, as measured by [3H]thymidine incorporation, was inhibited by IL-4 from 20 to 68% in a dose-dependent manner. A neutralizing antibody to human IL-4 was able to reverse the growth inhibitory effect of IL-4. Normal human fibroblast and endothelial cell lines also expressed high affinity IL-4R, however, IL-4 did not inhibit their growth in vitro. In fact, IL-4 caused modest stimulation of their growth. Taken together, our findings can help develop strategies for the treatment of RCC in which IL-4R may be used as a target for IL-4 itself, for IL-4 toxin therapy or, alternatively, in gene therapy.
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PMID:Expression of high affinity interleukin-4 receptors on human renal cell carcinoma cells and inhibition of tumor cell growth in vitro by interleukin-4. 842 37

Glucocorticosteroids (GCS) are beneficial in allergic asthma. GCS therapy results in reduced mRNA expression of interleukin-4 (IL-4) and IL-5 in cells from bronchoalveolar lavage (BAL) but not of IFN-gamma. In vitro studies with blood-derived T cells, however, show inhibition of all three cytokines by GCS. We studied the effects of GCS on T cells from BAL in vitro, namely Th0-, Th1, and Th2-like clones; and we compared BAL- with blood-derived clones. Dexamethasone (DEX) inhibited the anti-CD3-induced production of IL-4, IL-5 and IFN-gamma in all 20 clones tested. IFN-gamma production was inhibited significantly less than IL-4 and IL-5. DEX enhanced the ratio IFN-gamma/IL-4 (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005). Interestingly, two categories of clones were distinguished based on the effects of GCS on IL-2 production and IL-2R alpha expression and proliferation; 1) In low IL-2 producers DEX blocked IL-2 production and decreased IL-2R alpha expression and proliferation; 2) In high IL-2 producers DEX inhibited IL-2 production partially and enhanced IL-2R alpha expression and proliferation. Anti-IL-2 and anti-IL2R alpha blocked the DEX-induced increase in proliferation. High levels of added IL-2 induced the second type of response. In conclusion, the production of IL-4 and IL-5 by T-cell clones (derived either from BAL or blood) was more sensitive to inhibition by DEX than that of IFN-gamma, which may account for the therapeutic effects of glucocorticosteroids in patients with asthma. The differential effects of DEX on the proliferation of high and low IL-2 producers in vitro may implicate a selective outgrowth of Th1-like T cells in vivo in patients treated with steroids.
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PMID:Glucocorticosteroids affect functions of airway- and blood-derived human T-cell clones, favoring the Th1 profile through two mechanisms. 860 Sep 44

Human interleukin-4 (huIL-4) has been shown to inhibit the growth in vitro of cells from patients with acute lymphoblastic leukemia (ALL). With the aim of determining whether this cytokine might be useful in the treatment of patients with ALL, the effects of huIL-4 on human B-cell precursor ALL engrafted in severe combined immunodeficient (SCID) mice were examined. The inhibition of [3H] thymidine uptake of primary ALL cells by huIL-4 was maintained following engraftment and passage of leukemia in SCID mice. Five of seven xenograft leukemias showed significant inhibition in vitro by huIL-4 at concentrations as low as 0.5 ng/mL; furthermore, huIL-4 counteracted the proliferative effects of IL-7. When used to treat two human leukemias engrafted in SCID mice, huIL-4 200 microgram/kg/d, as a continuous 14-day subcutaneous infusion, suppressed the appearance of circulating lymphoblasts and extended survival of mice by 39% and 108%, respectively, the first demonstration of IL-4 activity against human leukemia in vivo. The mean steady-state huIL-4 level in mouse plasma during the infusion was 1.46 ng/mL (SEM +/- 0.14 ng/mL), which was similar to concentrations found to be effective in vitro. ALL cells obtained from mice relapsing after huIL-4 treatment continued to show inhibition by the cytokine in vitro. These data suggest that IL-4 may be useful in the treatment of patients with ALL.
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PMID:Interleukin-4 enhances the survival of severe combined immunodeficient mice engrafted with human B-cell precursor leukemia. 863 51

To identify the immunologic mechanisms that influence susceptibility to GN, we compared the severity of accelerated anti-glomerular basement membrane (GBM) nephritis between Lewis (LEW) and Brown Norway (BN) rats and analyzed differences in their immune responses to the nephritogenic immunoglobulin. Lewis (LEW) rats preimmunized with sheep IgG developed proliferative GN with marked proteinuria [peak protein excretion (mean +/- SEM) = 85.3 +/- 15.3 mg/24 hr; normal = 6.4 +/- 0.8 mg/24 hr] after receiving a subnephritogenic dose of sheep anti-rat GBM antiserum. Identically treated Brown Norway (BN) rats, on the other hand, had minimal renal pathology and minimal proteinuria (peak protein excretion = 22.6 +/- 3.1 mg/24 hr; normal = 13.0 +/- 0.6 mg/24 hr). Serum titers of rat anti-sheep IgG isotypes and intraglomerular binding of sheep IgG, rat IgG, and rat complement (C3) were comparable in both strains. In contrast, only LEW rats developed a strong cellular immune response to sheep IgG represented by intrarenal T lymphocyte (OX19+) and monocyte (ED1+) accumulation [LEW vs. BN (mean +/- SEM): OX19+ = 0.60 +/- 0.10 vs. 0.14 +/- 0.01 cells/glomerulus, control = 0.02 +/- 0.01; ED1+ = 4.0 +/- 0.4 vs. 1.0 +/- 0.2 cells/glom., control = 0.8 +/- 0.3] and a significant cutaneous delayed-type hypersensitivity (DTH) reaction [LEW versus BN (mean +/- SEM): delta ear thickness = 0.22 +/- 0.02 vs. 0.05 +/- 0.03 mm; control = 0.04 +/- 0.02 mm]. Upon rechallenge with sheep IgG in vitro, LEW splenocytes expressed a T helper 1 (Th1) cytokine pattern (IFN gamma and IL-2 mRNA, but little IL-4 mRNA) which is associated with delayed-type hypersensitivity reactions. BN splenocytes, on the other hand, expressed IL-4 in addition to IL-2 and IFN gamma mRNA that is consistent with an undifferentiated (Th0) cytokine profile. These studies suggest that humoral immunity to heterologous immunoglobulin planted in the kidney is not sufficient for full expression of accelerated anti-GBM nephritis, and that additional cellular immune mechanisms are required. We conclude that susceptibility to accelerated anti-GBM nephritis is strongly influenced by the host's propensity to mount a Th1-type response and DTH reaction to the disease-inciting immunoglobulin.
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PMID:Immunologic determinants of susceptibility to experimental glomerulonephritis: role of cellular immunity. 906 95


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