Gene/Protein Disease Symptom Drug Enzyme Compound
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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

Cytokines, interleukin-1 (IL-1), tumor necrosis factor alpha, and the neurotransmitter, substance P, have been implicated in the pathogenesis of arthritis because they stimulate synovial cells to secrete prostaglandin E2 and collagenase in vitro. We investigated in vivo changes in intraarticular substance P and the degradation of cartilage proteoglycan in response to intraarticular cytokine injections in rabbits. Twenty-four hours after a single injection of 10 ng, 30 ng, or 100 ng of recombinant human IL-1 alpha (rHuIL-1 alpha) per joint, the mean +/- SEM levels of substance P detected in the cell-free joint lavage fluid were 250 +/- 67 fmoles, 480 +/- 60 fmoles, and 530 +/- 130 fmoles (n = 4-5), respectively. The level of substance P in the contralateral knees injected with diluent was 58 +/- 8 fmoles (n = 12). The level of substance P had increased by 2 hours after IL-1 injection and remained elevated in the joint 48 hours after injection. Cytokine-induced proteoglycan depletion was also time- and dose-dependent. Proteoglycan concentrations in articular cartilage dissected from the weight-bearing condyles were calculated as the ratio of sulfated glycosaminoglycan measured using 1,9-dimethylmethylene blue: hydroxyproline. After 48 hours, 10 ng, 30 ng, or 100 ng of rHuIL-1 alpha per joint decreased proteoglycan levels by 9 +/- 4%, 14 +/- 4%, and 21 +/- 3% (n = 8), respectively. Likewise, the injection of recombinant human tumor necrosis factor alpha induced depletion of intraarticular substance P and cartilage proteoglycan.
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PMID:Elevated substance P and accelerated cartilage degradation in rabbit knees injected with interleukin-1 and tumor necrosis factor. 169 99

To evaluate potential adverse effects of acetate use in hemodialysis (HD), we measured plasma interleukin (IL-1 alpha, IL-1 beta, IL-6), TNF alpha, TGF beta 1, and beta 2-microglobulin levels with ELISA assays in normal (N = 9), CRF (N = 6), CAPD (N = 7) and HD (N = 8) subjects and compared the effects of acetate (Ac) and acetate-free (Ac-free) dialysate. TGF beta 1 was the only cytokine consistently detected. Compared to normals (median 57, range 53 to 68 pg/ml, one undetected; N = 8), TGF beta 1 was higher in the CRF (75, 70 to 97 pg/ml, one undetected) and CAPD (75.5, 66 to 116 pg/ml, N = 6) groups (P less than 0.05), and was somewhat higher in the HD (68, 52 to 88 pg/ml) group (P less than 0.10). Acutely, TGF beta 1 pre-HD (70, 63 to 88 pg/ml) increased above normals post AcHD [79.5, 65 to 140 pg/ml uncorrected for ultrafiltration (UF)] and was higher after AcHD versus Ac-free HD both uncorrected (79.5, 65 to 140 pg/ml vs. 70, 52 to 86 pg/ml) and corrected for UF (68, 51 to 115 pg/ml vs. 57, 43 to 69 pg/ml; P less than 0.05). beta 2-microglobulin was not different after AcHD (81.2 +/- 8.0 mg/ml) versus Ac-free HD (72.5 +/- 6.9 mg/ml). Significantly lower serum inorganic phosphorus was also found four hours post-AcHD compared to four hours post-Ac-free HD (0.87 mmol +/- 0.10 SEM vs. 1.05 mmol +/- 0.07 SEM; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of acetate dialysate on transforming growth factor beta 1, interleukin, and beta 2-microglobulin plasma levels. 176 11

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

The levels of 3 bone resorptive cytokines, interleukin 1 alpha (IL-1 alpha), IL-1 beta, and tumor necrosis factor alpha (TNF alpha), were assessed in tissues from sites of periodontal disease. As determined by ELISA of tissue extracts, IL-1 beta and TNF alpha were detected in all diseased sites, whereas IL-1 alpha was present in 8/22 sites, IL-1 beta was present in highest concentration (mean +/- SEM: 11,695 +/- 2,888 pg/ml; 672 pM), followed by TNF alpha (434 +/- 135 pg/ml; 26 pM), and IL-1 alpha (342 +/- 160 pg/ml; 20 pM). The levels of all 3 mediators were significantly lower in clinically healthy tissues. There was a highly significant correlation between levels of IL-1 beta and TNF alpha (rs = 0.61, P less than 0.001), suggesting coordinated expression of these 2 mediators. The numbers of cells containing each mediator was also determined by indirect immunofluorescence on frozen tissue sections. Consistent with findings from tissue extracts, IL-1 beta-containing cells were present in approximately 5-fold higher numbers than TNF alpha-containing cells, and 40-fold higher numbers than IL-1-alpha-containing cells. Taken together with previous findings, these results indicate that IL-1 beta is likely to be an important mediator in the pathogenesis of periodontal disease.
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PMID:Tissue levels of bone resorptive cytokines in periodontal disease. 192 18

Interleukin-1 alpha (IL-1 alpha) and interleukin-2 (IL-2) levels were measured by radioimmunoassay in samples of conditioned medium from mononuclear cells taken from 20 normal subjects (14 adults ranging in age from 20 to 45 years and 6 children ranging in age from 3 to 11 years) and from 49 children with growth delay. Cultures were performed with 10(6) cells/ml in medium containing 1% normal human serum and 4.8 g/l phytohemagglutinin M. The incubation was performed for 48 h in an atmosphere containing 5% CO2. In normal subjects, the production of IL-1 alpha was 38.5 +/- 9.8 fmol/ml of conditioned medium (mean +/- SEM) in 14 adults and 41.6 +/- 3.0 fmol/ml in 6 children. The production of IL-2 was 46.9 +/- 6.5 and 57.3 +/- 10.5 fmol/ml, respectively. In the 16 patients with growth hormone (GH) deficiency studied before treatment, the production of ILs was significantly decreased in relation to the degree of deficiency. We observed a positive correlation between the production of IL-1 alpha and the values of insulin-like growth factor I but not with serum GH values. IL-1 alpha production was normalized after 15 days of substitutive GH therapy and IL-2 was normalized after 3 months of therapy. In 10 other patients with GH deficiency (4 with total and 6 with partial isolated GH deficiency) studied after long-term GH treatment (5 months or more), the mean of IL production was not significantly different from that of GH-deficient children treated for 3 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Production of interleukin-1 alpha and interleukin-2 by mononuclear cells from children with growth delay in relation to the degree of growth hormone deficiency: effects of substitutive treatment. 210 Feb 77

The two forms of interleukin-1, IL-1 alpha and IL-1 beta respectively, and tumour necrosis factor (TNF) are polypeptides sharing different biological activities which are often associated with host defence mechanisms. Because of the well-recognized benefits of breast feeding for newborns, colostrum from 9 healthy lactating women was analysed for the presence of these 3 cytokines. Specific radioimmunoassay revealed that colostrum contains a significant amount of IL-1 beta (mean +/- SEM values of 1,130 +/- 259 pg/ml). The concentrations of IL-1 alpha and TNF were negligible. Colostral leukocytes are able to produce IL-1 since high activity was found after stimulation with Staphylococcus epidermidis. In addition, these cells produced IL-1 spontaneously in vitro, in contrast to resting maternal blood monocytes. As IL-1 increases resistance to infection, the presence of this cytokine represent a beneficial aspect of breast feeding.
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PMID:Interleukin-1 beta in human colostrum. 228 96

In this study, we have explored the relationship between interleukins and human basophil activation. Previous studies by ourselves and others have found that recombinant human (rh) IL-3 causes histamine release. The ability to release histamine has also been claimed for IL-1 but we cannot confirm this. In experiments with the basophils of 29 donors (excluding one D2O responder), histamine release with 100 ng/ml rhIL-1 alpha was 1.3 +/- 1% (SEM), whereas with rhIL-1 beta, it was 0.8 +/- 1%. Both IL-1 alpha and -1 beta were also used at concentrations of 0.01 to 1000 ng/ml without causing release. Neither increasing the Ca2+ concentration nor adding D2O or cytochalasin B caused IL-1 alpha and -1 beta to become secretagogues. rhIL-1, however, did augment IgE-dependent histamine release. The enhancement was similar with both rhIL-1 alpha and -1 beta, i.e. they were dose-dependent between 0.1 and 3 ng/ml and reached a plateau from 3 to 100 ng/ml. At submaximal histamine release (less than 10%), there was enhancement of three IgE-dependent secretagogues: 125% with goat anti-human IgE (n = 7), 215% with Ag E (n = 10), and 260% with a histamine releasing factor (n = 7). Non-IgE-dependent stimuli (formyl-methionine-leucine-phenylalanine and the ionophore A23187, n = 10) were enhanced less than 5%. rhIL-1-enhancement persisted after cell washing (n = 10). rhIL-1 was active in preparations of 50 to 75% pure basophils in which mononuclear cells were reduced by greater than 95% (n = 4), and mAbH34 to IL-1 beta blocked the enhancement caused by that molecule. We postulate that basophils have an IL-1 receptor which, when occupied, upregulates the response to IgE-related signals. Thus, this work characterizes a second interaction between interleukins and the cells central to the allergic response.
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PMID:Recombinant human IL-1 alpha and -1 beta potentiate IgE-mediated histamine release from human basophils. 247 85

The administration of interleukin 2 (IL-2) to mice and humans is limited by the induction of a dose-dependent increase in vascular permeability causing a vascular leak syndrome (VLS). We have investigated the impact of the injection of recombinant interleukin 1 alpha (IL-1 alpha) on the VLS induced by IL-2 by measuring the extravasation of 125I-albumin into tissues and by assessing wet and dry lung weights. IL-1 alpha alone did not induce any significant extravasation of radiolabeled albumin. IL-2 alone, however, caused a significant increase in the extravasation compared to control lungs. IL-1 alpha injection along with IL-2 significantly reduced the IL-2-induced extravasation of radiolabeled albumin [9,886 +/- 533 (SEM) cpm were observed in IL-2 and IL-1 alpha-treated lungs compared to 14,172 +/- 2,628 cpm in lungs treated with IL-2 alone (P less than 0.02)]. IFN-alpha in combination with IL-2 produced more severe vascular leakage than caused by IL-2 alone. IL-1 alpha also significantly decreased (P less than 0.05) the vascular permeability induced by the combination of IFN-alpha and IL-2. We observed 44,811 +/- 13,131 cpm in IFN-alpha- and IL-2-treated lungs compared to 18,350 +/- 2,622 cpm in IFN-alpha-, IL-2-, and IL-1 alpha-treated lungs. The IL-2- and IFN-alpha-induced increase in lung water weight was also reduced significantly by the addition of IL-1 alpha. The decrease in vascular leakage was dependent on the dose and timing of IL-1 alpha administered. When recombinant IL-1 alpha was given as a single i.p. injection, 24 h before the injection of IL-2 (or Hanks' balanced salt solution) or IL-2 and IFN-alpha no abrogation of the VLS was observed. Although IL-1 alpha decreased VLS significantly in mice treated with IFN-alpha and IL-2 the survival of mice was not improved by the simultaneous administration of IL-1 alpha. Histologically, treatment with IFN-alpha and IL-2 produced marked perivascular and intraalveolar edema which was completely eliminated by the addition of IL-1 alpha. However, some perivascular edema in IL-1 alpha-treated mice remained which was equivalent to that caused by IL-2 alone. Treatment of MCA-106 induced pulmonary metastases was enhanced by the administration of IFN-alpha and IL-2 together.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Decrease in interleukin 2-induced vascular leakage in the lungs of mice by administration of recombinant interleukin 1 alpha in vivo. 278 61

Native human IL-1 beta and IL-1 alpha stimulated prostaglandin E2 secretion by human embryonic lung fibroblasts at half-maximal concentrations of 3 +/- 1.2 pM (+/- SEM) and 10 +/- 2.3 pM, respectively. In contrast to the 20-50-fold lower affinities previously found for IL-1-R on 3T3 cells as well as murine and human lymphoblastoid lines, monoiodo 125I-IL-1 beta bound to normal human fibroblasts with a Kd of 8.4 +/- 4.1 pM in direct binding experiments, and with a Ki of 11.2 +/- 2.8 pM in competitive binding experiments. IL-1 alpha bound to the receptor identified by 125I-IL-1 beta with a Ki of 50 +/- 18 pM. The receptor exhibited homogeneous affinity for IL-1 beta or IL-1 alpha. The receptor did not recognize IL-2, IFN-gamma, tumor necrosis factor alpha, a functionally related monokine, or bovine acidic fibroblast growth factor, a structurally related mediator. Comparison of the biological response curves and binding curves obtained for IL-1 alpha and IL-1 beta showed that they were parallel and that 10-15% occupancy of the estimated 3,000 sites by either species of IL-1 was sufficient to give half-maximal stimulation of prostaglandin E2 secretion. Thus, the amount of apparent signal amplification observed on fibroblasts was considerably lower than the 100-100,000 fold amplification previously reported for lymphoid lines. Crosslinking experiments revealed a major band with a corrected molecular mass of approximately 80 kD and a minor band of approximately 200 kD. Labeling of these bands was blocked by IL-1 beta and IL-1 alpha but not by IL-2, IFN-gamma, or tumor necrosis factor alpha. These results demonstrate that normal human embryonic lung fibroblasts bear IL-1-R of sufficiently high affinity to mediate their biological responsiveness to low picomolar concentrations of IL-1 beta and IL-1 alpha and are consistent with the existence of a single receptor mediating the biological properties of both human IL-1 species.
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PMID:Identification of a high-affinity receptor for native human interleukin 1 beta and interleukin 1 alpha on normal human lung fibroblasts. 294 68


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