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PubMedDate not supplied

[Concentration of interleukin-18, interleukin-1beta, soluble receptor for interleukin-1 (sIL-1RII) and C-reactive protein in patients with neuroborreliosis].

BACKGROUND AND PURPOSE: The aim of the present study was to determine the role of interleukin-18 (IL-18), interleukin-1beta (IL-1beta) and its soluble receptor sIL-1RII in the pathogenesis of neuroborreliosis as well as the usefulness of C-reactive protein (CRP) determination in the diagnosis and monitoring of treatment of Lyme neuroborreliosis. MATERIAL AND METHODS: The study group consisted of 20 patients with Lyme meningitis (age range 16-72 years, mean age 42.6 years). For measurements of IL-18, IL-1beta and sIL-1RII levels in serum and cerebrospinal fluid (CSF) the control group consisted of 10 healthy volunteers and 10 patients with infection of the central nervous system ruled out, respectively. Cytokines and sIL-1RII levels in serum and CSF were measured twice, before and after the 30-day treatment period. Serum and CSF levels of IL-18, IL-1beta and sIL-1RII were measured using ELISA, and CRP serum levels were measured using the immunoturbidimetric method. RESULTS: Before the treatment the concentration of IL-18, IL-1beta and sIL-1RII in serum as well as in CSF was significantly higher as compared to the controls. After the treatment end the level of IL-18, IL-1beta and sIL-1RII was reduced but the serum level of sIL-1RII and CSF level of IL-18 and sIL-1RII remained significantly higher than in the control group. The serum level of CRP was increased only in 15% of patients and after the treatment CRP concentration returned to a basal level (except one patient in whom CRP was slightly higher than in the control group). No correlation between CRP and IL-18, IL-1beta and sIL-1RII was observed. CONCLUSIONS: Our results confirm the involvement of IL-18, IL-1beta and sIL-1RII in the pathogenesis of neuroborreliosis and uselessness of CRP determination in the diagnosis of Lyme meningitis.

Adolescent↗
PubMed1988

Multiple sclerosis: effect of myelin basic protein on interleukin 1, interleukin 2 production and interleukin 2 receptor expression in vitro.

The production of interleukin 1 (IL-1) and interleukin 2 (IL-2) by peripheral blood mononuclear cells (PBMC) stimulated with human myelin basic protein (MBP) was assessed in vitro in multiple sclerosis (MS) patients in relapse, patients with other neurological diseases (OND) and healthy subjects. Myelin basic protein significantly increased both IL-1 and IL-2 production by PBMC from MS patients during relapse when compared to OND patients or healthy controls. The most efficient concentration of MBP for the induction of IL-1 and IL-2 was 50 micrograms/ml. The optimal IL-1 production occurred after 48 h of PBMC culture and optimal IL-2 production after 72 h of PBMC culture. Anti-Tac monoclonal antibody (MoAb) was used to study IL-2 receptor expression on the same sample of PBM used for IL-2 study in MS patients in relapse. In addition IL-2 receptor expression was studied in PBMC from chronic progressive MS patients. In both MS groups IL-2 receptor expression on PBMC stimulated with MBP appeared higher than in control groups, but these differences were not statistically significant. IL-2 receptor expression on cerebrospinal fluid lymphocytes (CSF-L) either unstimulated or MBP-stimulated was, however, significantly higher in both MS groups when compared to OND patients. These results confirm the presence of activated lymphocytes in the CSF of MS patients during active stages of disease and suggest that this activation may be related to expansion of MBP specific cells.

Adult↗
PubMed1986

Interleukin 1-dependent induction of both interleukin 2 secretion and interleukin 2 receptor expression by thymoma cells.

The macrophage-derived product, interleukin 1 (IL 1) is thought to play an important regulatory role in the proliferation of T lymphocytes; however, its mechanism of action is unknown. We describe in this report a variant subline of EL4 thymoma cells (EL4-6.1) that displays a high degree of responsiveness to IL 1. We show that recombinant IL 1 can induce both the secretion of interleukin 2 (IL 2) and the expression of IL 2 receptors (IL 2-R) by these cells. EL4-6.1 cells do not constitutively secrete IL 2, nor do they express IL 2-R; but when cultured in the presence of recombinant IL 1, they secrete detectable amounts of IL 2 (5 to 15 U/ml). In the presence of either suboptimal levels of phorbol ester (PMA) or Ionomycin, the addition of IL 1 resulted in up to an 80-fold enhancement in the amount of IL 2 secreted. Stimulation with IL 1 alone or in combination with Ionomycin was unable to induce detectable IL 2-R expression by EL4-6.1 cells. However, in the presence of suboptimal concentrations of PMA, IL 1 induced expression of about 3000 high affinity (dissociation constant, Kd of 31 pM) and 50,000 low affinity (Kd of 2800 pM) IL 2-R. These IL 2-R were functional, based on their ability to rapidly internalize IL 2. This model system will allow a detailed analysis of the mechanisms involved in the regulation of the immune response by IL 1 and IL 2.

Animals↗
PubMed1985

Induction of interleukin 2 responsiveness in thymocytes by synergistic action of interleukin 1 and interleukin 2.

Thymocyte cultures from C3H/HeJ mice were stimulated for proliferative responses with purified preparations of interleukin 1 (IL 1) and interleukin 2 (IL 2). Synergistic responses were obtained in the absence of mitogen. In the presence of excess IL 2, the thymocyte proliferation response was strictly dependent on the amount of IL 1 in the cultures. Antibodies to IL 1 inhibited the response in a dose-dependent manner. The combination of IL 1 plus IL 2 induced the appearance of IL 2 receptors on murine thymocytes as detected with a monoclonal antibody directed against the IL 2 receptor. Neither IL 1 nor IL 2 alone had this effect. The thymic subpopulation found to become IL 2 responsive upon IL 1 stimulus was the peanut agglutinin-negative (PNA-) medullary fraction.

Animals↗
PubMed1994

Influence of corticosteroid pulse therapy on the serum levels of soluble interleukin 2 receptor, interleukin 6 and interleukin 8 in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the influence of corticosteroid pulse (CP) therapy on soluble interleukin 2 receptor (sIL-2R), interleukin 6 (IL-6) and IL-8 levels in patients with active rheumatoid arthritis (RA). METHODS: Twenty-five patients with active RA were studied before and after treatment with intravenous CP therapy. In 12 patients lymphocyte subsets were also assessed. RESULTS: All patients showed a significant decrease in clinical disease activity variables after 4 to 8 weeks of CP therapy. Baseline levels of sIL-2R were higher among patients with active RA than healthy controls; after CP therapy, sIL-2R levels decreased significantly, but not as much as the erythrocyte sedimentation rate or C-reactive protein. In most cases baseline levels of both IL-6 (n = 23) and IL-8 (n = 17) could be measured and both decreased significantly after CP therapy. Cortisol levels were suppressed shortly after CP therapy but had returned to pretreatment values at 4 weeks. After CP therapy there was a temporary increase in the number of HLA-DR positive cells and a decrease in the number of CD3 positive cells, while the CD4/CD8 ratio and IL-2 receptor (CD25) positive cells remained unchanged. CONCLUSION: High dose corticosteroids influence serum levels of sIL-2R, IL-6 and IL-8 in patients with active RA.

Adult↗
PubMed1996

Differential regulation of interleukin-12- and interleukin-15-induced natural killer cell activation by interleukin-4.

The regulation of human natural killer (NK) cell activation is under the control of a network of regulatory signals provided by cytokines. In the present study, we investigated the functional interaction between interleukin (IL)-4 and two monocyte/macrophage-derived cytokines, IL-12 and IL-15, during the process of NK stimulation. Using freshly isolated human NK cells, we have demonstrated that IL-4 negatively regulates lymphokine-activated killer (LAK) activity induced by IL-15 against the NK-resistant Daudi target cells. In contrast, IL-4 had no effect on IL-12-stimulated LAK generation. The differential effect of IL-4 on NK cell activation by IL-12 and IL-15 correlates with its ability to increase or to down-regulate the level of tumor necrosis factor-alpha and interferon-gamma release by NK cells, respectively. In contrast, endogenous transforming growth factor-beta 1 does not appear to be involved in the IL-4 regulatory pathway. Furthermore, while IL-4 was found to decrease the basal expression of the IL-2 receptor beta subunit utilized by IL-15, it had no effect on the expression of the beta 1 chain of the IL-12 receptor compared to untreated cells. Northern blot analysis indicated that the IL-4 regulatory effect on NK lytic function was associated with its capacity to down-regulate granzyme B and perforin gene transcription in response to IL-15 and its failure to affect the expression of both gene's in response to IL-12. Together, these data suggest the existence of a distinct cross-talk between IL-4 and IL-15 or IL-12 signaling pathways during the regulation of human non-major histocompatibility complex-restricted cytotoxicity.

Blotting, Northern↗
PubMed1995

A novel chimeric protein composed of interleukin 13 and Pseudomonas exotoxin is highly cytotoxic to human carcinoma cells expressing receptors for interleukin 13 and interleukin 4.

Chimeric proteins provide a unique opportunity to target therapeutic bacterial toxins to a subset of specific cells. We have generated a new recombinant chimeric toxin composed of human interleukin 13 (hIL13) and a Pseudomonas exotoxin A (PE) mutant, PE38QQR. The hIL13-PE38QQR chimera is highly cytotoxic to cell lines derived from several human epithelial carcinomas such as adenocarcinoma of stomach, colon, and skin. The cytotoxic action of hIL13-PE38QQR, which can only occur upon internalization of ligand-receptor complex, is blocked by an excess of hIL13 but not of hIL2. This action is not solely hIL13-specific because an excess of hIL4 also blocks the cytotoxicity of hIL13-toxin. Conversely, hIL13 blocks the cytotoxicity of a hIL4-PE38QQR chimera. Binding studies showed that hIL13 displaces competitively 125I-labeled hIL4-PE38QQR on carcinoma cells. These results indicate that IL4 and IL13 compete for a common binding site on the studied human cell lines. Despite this competition, hIL4 but not hIL13 decreased protein synthesis in malignant cells susceptible to the cytotoxicity of both hIL13- and hIL4-PE38QQR. Our results suggest that a spectrum of human carcinomas express binding sites for IL13. Furthermore, hIL13 and hIL4 compete reciprocally for a form of the receptor that is internalized upon binding a ligand. Thus, cancer cells represent an interesting model for studying receptors for these two growth factors. Finally, hIL13-PE38QQR may be a useful agent in the treatment of several malignancies.

ADP Ribose Transferases↗
PubMed1999

Interleukin-1beta-converting enzyme/caspase-1 in human osteoarthritic tissues: localization and role in the maturation of interleukin-1beta and interleukin-18.

OBJECTIVE: To study the expression and production of interleukin-1beta-converting enzyme (ICE) in human normal and osteoarthritic (OA) cartilage and synovium, quantitate the level of ICE in OA chondrocytes, and examine the relationship between the topographic distribution of ICE, interleukin-1beta (IL-1beta), and IL-18, as well as apoptosis of chondrocytes. METHODS: The expression and synthesis of ICE were investigated in human normal and OA cartilage and synovial membrane using in situ hybridization and immunohistochemical methods. The intracellular level of ICE in OA chondrocytes was also measured by enzyme-linked immunosorbent assay (ELISA). Furthermore, the topographic relationship between the presence of ICE and mature IL-1beta and IL-18 was examined by immunohistochemistry, and apoptotic chondrocytes by the TUNEL technique. RESULTS: ICE was expressed and synthesized in both human synovial membrane and cartilage, with a significantly greater number of cells staining positive in OA tissue than in normal tissue. ICE production was preferentially located in the superficial and upper intermediate layers of articular cartilage. With a specific ELISA, a level of 230.2+/-22.5 pg/5 x 10(5) cells (mean +/- SEM) of ICE was found in OA chondrocytes. In cartilage, IL-1beta and IL-18 stained positive at a topographic location similar to that of ICE. The production of mature IL-1beta in OA cartilage explants and chondrocytes was completely blocked by treatment with a specific ICE inhibitor, which also markedly diminished the number of IL-18-positive cells. The data show that there was no close relationship between the presence of ICE and the presence of apoptotic chondrocytes in OA cartilage. CONCLUSION: This study shows, for the first time, the presence of active ICE in human articular cartilage, with a markedly increased cellular level in OA tissue. The relationship between active IL-1beta and ICE suggests that ICE may promote OA progression by activating this proinflammatory cytokine. The role of IL-18 in pathologic cartilage is discussed.

Adult↗
PubMed2004

Gingival and dermal fibroblasts produce interleukin-1 beta converting enzyme and interleukin-1 beta but not interleukin-18 even after stimulation with lipopolysaccharide.

Epithelial cells play a critical role in periodontal disease through the secretion of pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and interleukin-18 (IL-18). However, the role played by fibroblasts is still unclear. The rationale of this study was to throw light on the role of gingival fibroblasts in periodontal disease. We thus investigated the expression of IL-1 beta, IL-18, and ICE mRNA and the secretion of the corresponding proteins by human normal gingival fibroblasts before and after stimulation with lipopolysaccharide (LPS) from Porphyromonas gingivalis and Escherichia coli. IL-1 beta, IL-18, and ICE mRNA expression was evaluated by RT-PCR. Proteins were analyzed by Western blot and ELISA. We demonstrated that gingival fibroblasts expressed ICE mRNA. Basal expression of ICE was modulated following cell stimulation with lipopolysaccharide (5 mug/ml). However, gingival fibroblasts expressed low levels of IL-1 beta mRNA. The expression was potentiated by LPS. The expression of IL-1 beta mRNA was followed by the secretion of IL-1 beta but not IL-18 protein. Our study suggests that fibroblasts may be involved in the defense against infections via an IL-1 beta-mediated but not an IL-18-mediated mechanism.

Adult↗
PubMed1991

Defective production of interleukin 6 by macrophages from C3H/HeJ mice: differential stimulation of interleukin 1 and interleukin 6 induction.

Resident macrophages from lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice, in contrast with macrophages from other mouse strains, produced neither interleukin 6 (IL-6) nor interleukin 1 (IL-1) spontaneously. The stimulation of C3H/HeJ macrophages with poly(I:C), LPS or, to a lesser extent, muramyl dipeptide (MDP), induced the production of both cytokines. High levels of intracellular IL-1 activity were produced which were not released in surrounding media unless silica was added to stimulated cells. On the other hand, IL-6 was secreted in the absence of any additional stimulus, hence also in the absence of extracellular IL-1. The kinetics of IL-1 and IL-6 production by LPS-stimulated macrophages were studied. Intracellular IL-1 produced by stimulated C3H/HeJ macrophages reached the levels produced by macrophages from C3H/HeN mice. IL-6-induced secretion, however, was about 5-fold less important than in C3H/HeN macrophages, suggesting a quantitative defect rather than an intrinsic defect in IL-6 production.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1998

Differential induction of interleukin-12, interleukin-18, and interleukin-1beta converting enzyme mRNA in experimental autoimmune encephalomyelitis of the Lewis rat.

Experimental autoimmune encephalomyelitis (EAE) is a model of autoimmune central nervous system (CNS) disease that is mediated by autoreactive Th1 cells secreting the proinflammatory cytokine interferon (IFN)-gamma. Interleukin (IL)-12 in its heterodimeric p35/p40 isoform and the recently described cytokine IL-18 potently induce T cell production of IFN-gamma. Interleukin-1beta converting enzyme (ICE) is required to convert IL-18 precursor protein into its biologically active mature form. In this study, we used semiquantitative reverse transciptase-polymerase chain reaction to determine steady state levels of IL-12, IL-18, and ICE mRNA in the spinal cord of Lewis rats at different stages of EAE. In control rats, we found significant IL-18, ICE, and IL-12p35, but not IL-12p40 mRNA expression. IL-18 mRNA increased during the acute stage of EAE together with a marked induction of ICE mRNA. IL-12p35 mRNA levels did not change significantly throughout the course of EAE. Surprisingly, the peak expression of IL-12p40 mRNA was delayed by several days relative to the peak of T cell infiltration and IFN-gamma mRNA synthesis. Our data implicate the IL-18/ICE pathway in the amplification of Th1-mediated immune responses in the CNS but suggest a different, so far undefined role of endogenous IL-12 in the late effector phase of EAE.

Animals↗
PubMed2003

Polymorphism in intron 2 of the fetal interleukin-1 receptor antagonist genotype influences midtrimester amniotic fluid concentrations of interleukin-1beta and interleukin-1 receptor antagonist and pregnancy outcome.

OBJECTIVE: Preterm labor in experimental models is initiated by intra-amniotic interleukin-1beta (IL-1beta) and inhibited by interleukin-1 receptor antagonist (IL-1ra). The IL-1ra gene is polymorphic and the different alleles are associated with variations in IL-1beta and IL-1ra production. The relationship among the IL-1ra genotype of the fetus, concentrations of IL-1beta and IL-1ra in second-trimester amniotic fluid, and pregnancy outcome was determined. STUDY DESIGN: Amniotic fluids from 291 consecutive women with singleton pregnancies, obtained at 15 to 17 weeks' gestation, were tested for IL-1beta and IL-1ra concentrations by enzyme-linked immunosorbent assay. DNA from fetal cells was analyzed for a length polymorphism in intron 2 of the IL-1ra gene by polymerase chain reaction. Pregnancy outcomes were obtained after completion of testing. RESULTS: The distribution of fetal IL-1ra genotypes was similar to that found in other populations: 50.9% (148) were homozygous for allele 1 (IL1RN*1), 39.5% (115) were IL1RN*1/allele 2 (IL1RN*2) heterozygotes, 6.9% (20) were IL1RN*2 homozygotes, whereas 2.7% (8) had combinations of other alleles. Fetal possession of IL1RN*2 was associated with a greater than 50% increase in midtrimester intra-amniotic IL-1beta levels (P=.006) and a smaller increase in IL-1ra levels (P=.01) compared with fetuses who were IL1RN*1 homozygotes. Despite the low sample size, IL1RN*2 homozygosity, but not midtrimester intraamniotic levels of IL-1beta and IL-1ra, was related to an increased rate of preterm birth (P<.0001). In the 11 pregnancies that were subsequently terminated because of major malformations, there was a decreased frequency of IL1RN*1 homozygosity (P=.04). Birth weight was unrelated to IL-1ra genotype. CONCLUSION: Possession by the fetus of the IL1RN*2 allele is associated with enhanced intraamniotic IL-1beta production. Induction of an intra-amniotic proinflammatory immune response might be more likely to lead to preterm labor in fetuses carrying the IL1RN*2 allele.

Amniotic Fluid↗
PubMed1991

Diphtheria toxin receptor-binding domain substitution with interleukin 6: genetic construction and interleukin 6 receptor-specific action of a diphtheria toxin-related interleukin 6 fusion protein.

We have genetically replaced that portion of the diphtheria toxin structural gene which encodes the native receptor-binding domain with a synthetic gene encoding the cytokine interleukin 6 (IL-6/IFN-beta 2/BSF-2). The resulting gene fusion encodes the chimeric toxin DAB389-IL-6. Following expression and purification, we demonstrate that DAB389-IL-6 is selectively cytotoxic for eukaryotic cells bearing the interleukin 6 receptor. In addition, the cytotoxic action of DAB389-IL-6 is shown to require binding to the IL-6 receptor, internalization by receptor-mediated endocytosis and passage through an acidic compartment. Following the delivery of the catalytically active fragment A to the cytosol of target cells, cellular protein synthesis is inhibited by the ADP-ribosylation of elongation factor 2. While eukaryotic cells which are devoid of the IL-6 receptor are uniformly resistant to the action of this fusion toxin, the data presented suggest that a minimal number of IL-6 receptors may be necessary to mediate the internalization of sufficient levels of DAB389-IL-6 to result in the intoxication of target cells.

Animals↗
PubMed1985

Dissociation between interleukin-1 and interleukin-2 production in proliferative response to microbial antigens: restorative effect of exogenous interleukin-2.

The relationship between the production of interleukin-1 (IL-1) and interleukin-2 (IL-2) after stimulation of human mononuclear cells within an antigenic extract from Candida albicans was analyzed in both responder and nonresponder donors. Culture supernatants from responders contained both IL-1 and IL-2 activity, whereas the supernatants from nonresponders contained only IL-1 and no appreciable IL-2. However, the addition of exogenous IL-2 to nonresponder cultures restored the normal proliferative response. Similar observations were made when cells from mice infected intravenously with high doses of Mycobacterium bovis BCG were cultured; these cells showed a marked impairment of the proliferative response to purified protein derivative. Spleen cells from BCG-induced unresponsive mice failed to produce IL-2 despite the fact that normal IL-1 activity was present in the culture. Again, the addition of exogenous IL-2 fully reversed the proliferative unresponsiveness. Thus, the presence of IL-1 does not necessarily induce production of IL-2, and the proliferative unresponsiveness is therefore due to a primary lack of IL-2.

Animals↗
PubMedDate not supplied

Interleukin-1 alpha reduces the severity of the vascular leak syndrome produced by interleukin-2 and interleukin-2 plus interferon-alpha.

Histological and ultrastructural changes were investigated in lung, liver, and heart of mice given interleukin-2 (IL-2), either alone or in combination with other cytokines. IL-2 induced a vascular leak syndrome (VLS) of a moderate degree with infiltration of lymphoid cells, moderate endothelial damage, mild hepatic parenchymal damage, and minimal myocardial alterations. Interferon-alpha (IFN-alpha) produced infiltration mainly of monocytes/macrophages in liver and heart; endothelial cell damage was absent in lung and heart and minimal in liver. Interleukin-1 alpha (IL-1 alpha) caused an increased number of neutrophils in liver and lung; VLS and parenchymal cell and endothelial damage were not found. The VLS and the cellular damage caused by the combination of IL-2 and IFN were much more severe than those produced by IL-2 alone. In animals treated with IL-2, IFN-alpha, and IL-1 alpha, VLS was minimal and parenchymal and endothelial cell damage were less severe than after IL-2 alone or IL-2 plus IFN-alpha. Taken together, these observations show that IL-1 alpha reduces ultrastructural changes produced by IL-2 and IFN-alpha. This reduction may be clinically useful in the treatment of neoplasms.

Animals↗
PubMed2004

Interleukin-6, interleukin-10, and vascular endothelial growth factor in metastatic renal cell carcinoma: prognostic value of interleukin-6--from the Groupe Francais d'Immunotherapie.

PURPOSE: Few clinical prognostic factors have been identified for patients with metastatic renal cell carcinoma (MRCC), and no biomarker is known in this disease. Several endogenous cytokines have demonstrated interesting and significant correlations with survival in these patients. Our objective was to analyze the prognostic value of circulating vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), and interleukin-6 (IL-6). PATIENTS AND METHODS: Serum levels of IL-6, IL-10, and VEGF were measured in patients with MRCC. Their prognostic value for response to treatment and progression-free and overall survival was evaluated. Pretreatment samples were obtained from 138 patients of a large randomized multicentric trial. Endogenous cytokine levels were determined using immunoassays. Univariate and multivariate analyses were performed to evaluate the prognostic value of each factor further controlled by an internal validation test. Threshold values for serum IL-6 and VEGF were determined using the quartile method. RESULTS: Serum IL-6 was detectable in 70% of the patients. IL-10 and VEGF were elevated in 8% and 71% of the patients, respectively. None of these circulating factors was correlated with response to treatment. IL-10 was not significantly correlated with progression-free or overall survival. Despite significant correlation with survival, VEGF was not an independent prognostic factor in the multivariate analysis. Finally, IL-6 was significantly correlated with progression-free survival and overall survival, and has prognostic value for overall survival. CONCLUSION: Circulating IL-6 level appears to be an important independent prognostic factor in patients with MRCC; if confirmed in further studies, it could be considered for treatment decisions in these patients.

Adult↗
PubMed1991

Soluble interleukin 2 receptor release, interleukin 2 production, and interleukin 2 receptor expression in activated T-lymphocytes in vitro.

Following activation in vitro, peripheral blood mononuclear cells (PBMC) express cell-associated interleukin-2 receptors (IL2R). The present study was undertaken to define the proportion of T lymphocyte subsets that express the IL2R (CD25 antigen) upon different mitogenic stimulation. Double immunofluorescence staining with different fluorochromes, fluorescein isothiocyanate and phycoethyrin, was applied for identification of IL2R positive cells and individual lymphocyte subset. The exact percentage of individual activated lymphocyte subset bearing IL2R was enumerated by photographic counting. There was paucity of IL2R in freshly isolated, unstimulated peripheral blood, PBMC cultured without mitogen, and cultured B lymphocytes. Following pokeweed mitogen stimulation in vitro, 19% of CD4 (T-helper/inducer) lymphocytes and 14% of CD8 (T-suppressor/cytotoxic) lymphocytes expressed IL2R. Similarly, 25% of CD4 lymphocytes and 19% of CD8 lymphocytes expressed IL2R following phytohemagglutinin stimulation in vitro. Contrary to the reported data of Tac-positive cells in human lymphoid tissues, our study revealed that, upon lectin mitogen stimulation, approximately 55% of IL2R positive PBMC were CD4 lymphocytes, and 45% of them were CD8 lymphocytes. These observations imply the plausible notion that interleukin-2 mediated immune activation of T lymphocytes in PBMC is different from that in local lymphoid organs. It was also demonstrated that the release of soluble IL2R (sIL2R) and IL2 production in supernatant from cultured PBMC varied with different lectin stimulation. A significant correlation was demonstrated between the cellular and soluble IL2R but the production of IL2 from activated mononuclear cells bore no good correlation with either the cellular IL2R expression or the release of sIL2R.

Adult↗
PubMed1989

Interleukin 3 mediates interleukin 6 production in murine interleukin 3-dependent hemopoietic cells.

A series of murine interleukin 3 (IL-3)-dependent hemopoietic cell lines was studied for the capacity to produce interleukin 6 (IL-6) in vitro. These included a bone marrow-derived mast cell line (L138.8A) and several early myeloid cell lines described in the literature (DA-1, DA-3, NFS-60, NFS-78, FDC-P1, FDC-P2, FDC-PmixA4, and 32Dcl.23). All of these cell lines produced growth factor activity for IL-6-dependent hybridoma cells (7TD1), which was completely neutralized by the monoclonal anti-IL-6-antibody 6B4. IL-6 expression was also evident at the mRNA level using a murine IL-6-specific cDNA probe. In 32Dcl.23 cells (2 x 10(5)/ml) stimulated for 24 hr with serial dilutions of purified murine IL-3, a positive correlation was found between the IL-3 dose and the amount of IL-6 measured in the conditioned media. At 24 hr this correlation was not evident at the mRNA level. However, prolonged exposure of 32Dcl.23 cells (up to 72 hr) to either a high (60 U/ml) or a low IL-3 concentration (1 U/ml) revealed a time-dependent increase and decrease, respectively, of IL-6 mRNA levels. At both IL-3 concentrations 32Dcl.23 cells remained in a fully viable and proliferative state. The influence of IL-3 on IL-6 release could be specifically counteracted by anti-IL-3-antiserum. IL-6 added alone or in concert with IL-3 did not stimulate 32Dcl.23 proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗