UMLS:C0432222 - FACTA Search

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

In this study, we have attempted to determine whether mouse peritoneal mast cells released histamine in response to IL-3. Recombinant mouse (m)IL-3 induced histamine release from mouse peritoneal mast cells in a dose-dependent fashion. Histamine release did not occur in the absence of phosphatidyl serine (PS), and was dependent on PS concentrations. The release was 14.3 +/- 3.8 and 43.5 +/- 11.5% (mean +/- SEM, n = 5) at 1 nM IL-3 in the presence of 10 and 20 micrograms/ml of PS. Calcium was required for the response, and in the absence of calcium, significant histamine release was not observed. The kinetics were slower than those of anti-IgE-induced response. IL-3-induced histamine release reached a peak within 15 min, while that by anti-IgE reached 80% of the maximum in 3 min. Lower concentrations of IL-3, which failed to directly induce histamine release, did not enhance anti-IgE-induced histamine release. Other cytokines, including mIL-4, mIL-5, m-granulocyte-macrophage colony-stimulating factor, human (h)IL-1 alpha, hIL-1 beta and hIL-8, neither induced histamine release nor enhanced anti-IgE induced histamine release. IL-4 had no capacity to enhance IL-3-induced histamine release. These results suggest that locally produced IL-3 might modulate mast cell-related inflammation through histamine release from mast cells.
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PMID:Mouse IL-3 induces histamine release from mouse peritoneal mast cells. 138 45

Tumor-infiltrating lymphocytes (TIL) were isolated from 22 human primary and metastatic liver tumors, and expanded in vitro in the presence of either interleukin-2 (IL-2, 100 U/ml) plus tumor necrosis factor alpha (TNF alpha, 1000 U/ml), IL-2 (1000 U/ml) plus IL-4 (1000 U/ml) or IL-2 (1000 U/ml) alone. TIL proliferated in culture in 20/22 cases. Among different cytoline combination, TNF alpha and IL-2 were most effective in promoting the outgrowth of CD3+CD8+T lymphocytes (mean +/- SEM: 90% +/- 5) in the cultures of TIL from primary liver tumors. Cytotoxicity against autologous tumor cells was demonstrated in all early cultures of TIL from primary liver cancers in the presence of IL-2 plus TNF alpha. In contrast, cultures of TIL derived from colon cancer metastatic to liver had significantly lower levels of autotumor cytotoxicity and proportions of CD3+CD8+ cells (40% +/- 13) than those of TIL from primary liver tumors. The addition on day 0 of interferons (alpha or gamma) to TIL cultured in the presence of TNF alpha and IL-2, significantly augmented cytotoxicity against autologous tumor. In contrast, incubation of TIL in the presence of IL-4 and IL-2 did not result in increased autotumor responses in the cultures of TIL from primary liver tumors. The expansion (-fold) of TIL (day 30) cultured in the presence of IL-2 alone compared to that in the presence of TNF alpha and IL-2 was significantly greater for hepatocellular carcinoma (median, 280 vs 260) than for autologous peripheral blood lymphocytes (36 vs 27), cholangiocarcinoma (42 vs 51) or TIL from metastatic colon cancer (39 vs 30). Outgrowth of TIL in IL-2 plus TNF alpha offers an opportunity for in vitro enrichment in cells with autotumor cytotoxicity in primary liver tumors. However, this cytokine combination was unable to promote and sustain growth of autotumor effectors from TIL in metastatic liver cancer.
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PMID:Effects of cytokines on in vitro growth of tumor-infiltrating lymphocytes obtained from human primary and metastatic liver tumors. 184 44

Juvenile chronic myelogenous leukemia (JCML) is a rare pediatric malignancy characterized by marked hepatosplenomegaly, leukocytosis with prominent monocytosis, elevated fetal hemoglobin, no Philadelphia chromosome, and generally a poor prognosis. In vitro, JCML peripheral blood granulocyte-macrophage progenitors (granulocyte-macrophage colony-forming units, CFU-GM) demonstrate the unique characteristic of "spontaneous" proliferation at very low cell densities in the absence of exogenous growth factors. The "spontaneous" CFU-GM proliferation can be abolished by prior adherent cell (monocyte) depletion, suggesting a paracrine mode of cellular proliferation. Although previous studies using a [3H]thymidine ([3H]TdR) incorporation assay suggested an important role for granulocyte-macrophage colony-stimulating factor (GM-CSF) in JCML, many non-growth factor-related reasons for [3H]TdR incorporation and the relatively low level of inhibition of [3H]TdR uptake left those conclusions open to question. Therefore, we performed clonal CFU-GM assays, which more specifically reflect cytokine effects on CFU-GM, using JCML peripheral blood mononuclear cells (PBMNC) and neutralizing antibodies against GM-CSF, granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating (M-CSF), interleukin 3 (IL-3), interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), interleukin 4 (IL-4), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF alpha), and interferon gamma (IFN gamma). Cultures containing anti-GM-CSF alone inhibited "spontaneous" JCML CFU-GM by 87% +/- 9% (mean +/- standard error of the mean [SEM]). No other anti-cytokine antibody produced a significant inhibition of CFU-GM growth. Various combinations of antibodies, excluding anti-GM-CSF, failed to demonstrate any synergistic inhibitory effects upon CFU-GM. Because this apparent paracrine cellular stimulation could be due to excessive cytokine production, by monocytes or other accessory cells, we examined cytokine levels in conditioned media from various JCML cell populations using enzyme-linked immunosorbent assays (ELISAs). Monocytes from only a minority of JCML patients produced higher than normal quantities of GM-CSF, G-CSF, IL-1 beta, IL-6, and/or TNF alpha, but no obvious pattern could be discerned. Further, only 7 of 15 JCML monocyte-conditioned media (MCM) had elevated GM-CSF, and 6 of 15 JCML patients had normal levels of all nine cytokines tested. The monocyte depletion experiments and the inhibition experiments with anti-cytokine antibodies taken together demonstrate clearly that the "spontaneous" growth of JCML CFU-GM in vitro critically depends on at least one monocyte-derived growth factor, GM-CSF.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of monocyte-derived hemopoietic growth factors in the regulation of myeloproliferation in juvenile chronic myelogenous leukemia. 191 2

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

As in humans, rabbit coronary artery endothelium basally expresses vascular cell adhesion molecule-1 (VCAM-1). Treatment with parenteral cyclosporine (CsA) to prevent graft rejection in rabbits receiving heterotopic heart transplantation reduced VCAM-1 expression in coronary arteries not only in transplanted, but also in native rabbit hearts. To explore the mechanism of this effect, we co-incubated cultured human saphenous vein endothelial cells for 24 hr with CsA or its vehicle (containing polyoxyethylated castor oil, or Cremophor, and ethanol), at concentrations compatible with those achievable in plasma during administration of parenteral preparations of CsA. Cells were then stimulated with TNF alpha or IL-4 to induce VCAM-1 expression, assessed by a cell-surface enzyme immunoassay. Both CsA and vehicle inhibited IL-4-stimulated VCAM-1 expression in a dose-dependent manner (from [OD mU, mean +/- SEM] 230 +/- 5 to 165 +/- 3 for CsA 50 ng/ml, and to 181 +/- 6 for the corresponding vehicle concentration; P < 0.05 for both comparisons). To investigate whether this vehicle effect also occurs in vivo, we treated 9 New Zealand White rabbits with saline (n = 3), CsA (10 mg/kg/day, n = 3), or vehicle at corresponding doses (n = 3) for 6 weeks. Profiles of coronary arteries (> or = 48 for each group) were semiquantitatively scored (0-5) for VCAM-1 in immunostained heart cross-sections. Administration of both CsA and vehicle significantly reduced VCAM-1 expression compared with saline. Two vehicle components, ethanol and ricinoleic acid, were further evaluated directly on endothelial cells in vitro. While ethanol was ineffective, the monounsaturated fatty acid ricinoleic acid inhibited IL-4-stimulated VCAM-1 expression in a dose-dependent manner (IC50 between 10 and 100 microM). Thus, a fatty acid component of CsA vehicle exerts direct endothelial effects, potentially limiting arterial leukocyte recruitment during parenteral CsA treatment. This observation reveals a novel mechanism for CsA as an inhibitor of leukocyte-endothelial interactions, and furnishes a new potential rationale for the therapeutic action of unsaturated fatty acids in graft coronary disease.
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PMID:The direct effect of injectable cyclosporine and its vehicle, cremophor, on endothelial vascular cell adhesion molecule-1 expression. Ricinoleic acid inhibits coronary artery endothelial activation. 754 37

The effects of interleukin (IL)-2, -3, -4, -5, -6, and -7 and granulocyte-macrophage colony-stimulating factor (GM-CSF) on histamine release from human basophils were evaluated. IL-3 was the only cytokine with histamine-releasing activity. This activity was observed predominantly on basophils from allergic patients (mean release +/- SEM, 33.9 +/- 9.5%; n = 12), whereas basophils from normal subjects responded less frequently to stimulation with IL-3 (mean release +/- SEM, 2.8 +/- 1.0%; n = 22). The effect of IL-3 was time and temperature dependent, since release was optimal after incubation for 120 min at 37 degrees C. When cell-bound IgE were eluted at acid pH, basophils became unresponsive to IL-3; however, IL-3-induced histamine release correlated with anti-IgE-induced histamine release in allergics, but not in normals. IL-3, IL-5, IL-6, and GM-CSF enhanced significantly anti-IgE- and FMLP-induced histamine release. In contrast, IL-2, IL-4, and IL-7 were devoid of any significant histamine-releasing or -potentiating activity. These results indicate that IL-3 can induce and IL-3, -5, and -6 and GM-CSF can enhance histamine release from human basophils, suggesting a possible role of these cytokines in the expression of allergic reactions.
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PMID:Inducing and enhancing effects of IL-3, -5, and -6 and GM-CSF on histamine release from human basophils. 768 60

mRNA and protein expression of the Th2 cytokines IL-4 and IL-5 from human lung were examined during the first 4 hr following IgE-mediated triggering, a time representative of the evolving late-phase reaction (LPR). Lung explants were incubated for 16 hr at 37 degrees C in culture media alone or with added dexamethasone (10(-6) M), washed, and then challenged with buffer or anti-IgE (3 micrograms/ml). Using RNase protection assays, in 16/16 individual lungs IL-5 mRNA expression was observed at 4 hr following anti-IgE and at no points following buffer challenge. Fragments released 1129 +/- 499 ng of IL-5/g wet wt over a 24-hr period (mean +/- SEM, n = 5). Neither IL-4 transcripts nor protein were detected in any anti-IgE challenges. Both the IgE-mediated IL-5 mRNA and protein responses were below the limits of detection following dexamethasone preincubation, suggesting a mechanism for the potent inhibitory effects of these agents observed in the LPR.
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PMID:IgE-dependent expression of interleukin-5 mRNA and protein in human lung: modulation by dexamethasone. 770 76

The cytokines interleukin-12 (IL-12) and IL-4 play important roles in the development of Th1-like (type-1) and Th2-like (type-2) T-cell responses, respectively, and there is evidence that type-1/type-2 T helper imbalances are important in the pathogenesis of human immunodeficiency virus (HIV) disease. With this background, we examined the effects of these cytokines on HIV replication. Neither stimulated HIV replication in fresh peripheral blood mononuclear cells (PBMC). However, in prestimulated PBMC, IL-12, and to a greater extent, IL-4 as well as IL-2, induced production of HIV p24 antigen over 7 days of culture (no cytokine 3,900 x/divided by 1.31 [GM x/divided by SEM] pg/mL; IL-12, 34,300 x/divided by 1.39 pg/mL; IL-4, 283,000 x/divided by 1.14 pg/mL; and IL-2, 328,000 x/divided by 1.31 pg/mL). Neither IL-12- nor IL-4-induced HIV replication was attributable to induction of IL-1, IL-2, tumor necrosis factor (TNF)-alpha, or TNF-beta. Both IL-12- and IL-4-induced HIV replication was associated with selective loss of the CD4+ subset in stimulated cultures. IL-4 stimulated HIV replication in monocyte/macrophages, while IL-12 had little or no effect in these cells. Finally, HIV replication stimulated by IL-12 or IL-4 was inhibited by dideoxynucleosides. Thus, IL-12 and IL-4 enhance HIV replication and HIV-induced cell death in prestimulated PBMC. Through killing of the CD4+ T cells stimulated by these cytokines, this may result in inappropriate type-1/type-2 responses in HIV-infected patients and contribute to their Th1 immunodeficiency.
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PMID:Effects of the Th1 and Th2 stimulatory cytokines interleukin-12 and interleukin-4 on human immunodeficiency virus replication. 771 82

A cell line, designated SEM, was established from the peripheral blood of a 5-year-old girl in relapse with acute lymphoblastic leukaemia (ALL). Both the lymphoblasts of the patient and the cells of the cell line SEM showed the t(4;11) chromosomal rearrangement. The analysis of the immunophenotype of the SEM cell line revealed the B-cell differentiation antigens CD19, CD22 and CDw75 in the absence of CD20, CD24 and immunoglobulin expression. Besides B-lineage antigens, SEM cells were positive for the myeloid antigens CD13, CD15, CD33 and CDw65. Immunogenotypic analysis of SEM cells showed a monoclonal rearrangement of immunoglobulin heavy-chain (IgH). T-cell receptor (TCR) gamma and delta genes. Addition of interleukin (IL)-7 promoted the growth of the patient's lymphoblasts in culture and enhanced the proliferation of SEM cells. The SEM cells also express messenger RNA (mRNA) for the IL-7 receptor (IL-7R), but no evidence for autocrine production of IL-7 by the cell line was found. Addition of IL-4, tumour necrosis factor (TNF)-alpha, interferon (IFN)-alpha, or IFN-gamma resulted in a profound inhibition of SEM growth. Thus, these cytokines may have important growth regulatory activities for biphenotypic leukaemic ALL cells.
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PMID:The acute lymphoblastic leukaemia cell line SEM with t(4;11) chromosomal rearrangement is biphenotypic and responsive to interleukin-7. 819 15

The mechanisms contributing to persistent T cell activation and poor response to glucocorticoids in chronic inflammatory illnesses such as steroid resistant (SR) asthma are poorly defined. We examined the possibility that certain cytokines, specifically IL-2 and IL-4, could affect T cell response to glucocorticoids. A [3H]dexamethasone radioligand-binding assay was used to measure the number of glucocorticoid receptors (GR) and dissociation constant (Kd) in PBMC from normal donors and patients with SR asthma, cultured in the absence and presence of these cytokines. PBMC from normal donors incubated for 48 h in the presence of combination IL-2 + IL-4 had nuclear GR with significantly reduced binding affinity (GR Kd = 36.1 +/- 1.63 nM, mean +/- SEM; p = 0.0001) as compared with PBMC incubated with medium alone (GR Kd = 6.74 +/- 0.46 nM). The cytosolic GR Kd remained unchanged. However, when PBMC were incubated with IL-2 alone or IL-4 alone, no change in GR-binding affinity was observed. Furthermore, when T cells and non-T cells were individually stimulated with combination IL-2 + IL-4, a significant reduction in GR-binding affinity was observed only in the T cell population (p = 0.0001). The IL-2 + IL-4-induced alteration in PBMC GR Kd was associated with an increase in GR number (8348 +/- 964 vs 1710 +/- 228 sites/cell; p = 0.0003). More importantly, the alteration in PBMC GR-binding affinity with IL-2 + IL-4 was associated with a functional change in T cell response to methylprednisolone MPN, i.e., a reduced inhibitory effect of MPN on PMA/ionomycin-induced T cell proliferation. These effects of IL-2 + IL-4 on PBMC GR affinity and response to MPN were blocked by co-incubation with IFN-gamma. Freshly isolated PBMC from four patients with SR asthma had a significantly reduced GR-binding affinity (Kd = 40.0 +/- 2.68 nM; p = 0.0001) when compared with seven normal subjects (7.15 +/- 0.41 nM). The altered PBMC GR binding from patients with SR asthma reversed to normal when incubated with medium alone, but was sustained with IL-2 + IL-4. These observations suggest that with persistent inflammation certain cytokines may contribute to an impaired response to glucocorticoids. Furthermore, the effects of IL-2 and IL-4 were blocked by IFN-gamma.
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PMID:Combination IL-2 and IL-4 reduces glucocorticoid receptor-binding affinity and T cell response to glucocorticoids. 837 86

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