Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 35 patients receiving first liver transplants we assessed the chemotactic responsiveness of peripheral blood lymphocytes to bile, the subset composition of the responding population and the ability of peripheral blood lymphocytes to produce chemotactic factors. In 13 patients in whom acute rejection developed, lymphocyte chemotaxis in vitro was significantly greater in bile sampled 1 or 2 days after transplantation and before episodes of acute rejection than in bile sampled when rejection was clinically apparent or after steroid therapy during stable graft function. The chemotactic factors present showed preferential activity for CD8-positive T cells. Bile sampled during the same posttransplant periods from 11 patients who did not exhibit rejection showed significantly less chemotactic activity. In vitro cultured peripheral blood lymphocytes from patients in whom rejection developed produced lymphocyte chemotactic factors that induced a similar pattern of chemotactic responsiveness with preferential activity for CD8-positive T cells. Separate culture of purified CD4-positive and CD8-positive T cells obtained from patients in whom rejection developed showed that CD4-positive cells produced the factor(s). Analysis of the subset responses of normal peripheral blood lymphocytes to a variety of chemotactic cytokines showed interleukin-6 to have specificity similar to that observed with chemotactic bile, mixed peripheral blood lymphocyte culture supernatants and supernatants of CD4-positive T cells. Chemotactic activity was reduced by 45% to 90% in five chemotactic bile samples and three peripheral blood lymphocyte culture supernatants by treatment with affinity purified interleukin-6 monoclonal antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Secretion of soluble chemotactic factors, including interleukin-6: a mechanism for the recruitment of CD8-positive T lymphocytes to human liver allografts during rejection. 835 94

Cancer remains the second most common cause of death in our society, and advanced disease is often refractory to surgical, chemotherapeutic, and radiologic interventions. One novel approach to cancer treatment involves targeting a cytotoxic agent to a cancer cell. Immunotoxins have been developed that contain a potent toxin (either Pseudomonas exotoxin, ricin toxin, or diphtheria toxin) coupled to a targeting moiety that directs the molecule to cells expressing a certain antigen. Chemically coupled immunotoxins have been developed over the past 12 years. These bind to and kill cells expressing many tumor-associated antigens. Initial clinical results were disappointing, but recent results have been more promising. Furthermore, newer immunotoxins have been developed that will soon be in clinical trials. Some of these are recombinant toxins that have been developed using techniques of genetic engineering. Transforming growth factor-alpha, acidic fibroblast growth factor, insulin-like growth factor-1, interleukin-2, interleukin-4, interleukin-6, the binding portions of monoclonal antibodies, and CD4 have been used to direct toxins to cancer cells or cells infected with the human immunodeficiency virus type 1. Efforts are under way to circumvent problems such as immunogenicity that may limit the clinical usefulness of immunotoxins.
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PMID:Immunotoxins and recombinant toxins in the treatment of solid carcinomas. 836 39

Serum cytokine levels and mononuclear cell subpopulations in the spleen and peripheral blood of patients with visceral leishmaniasis before and after antimony therapy were analyzed. The percentages of activated monocytes/macrophages, T cells, and possibly B cells; of gamma/delta T cell receptor (TCR)-bearing T cells; of CD4- CD8- alpha/beta TCR-bearing T cells; and serum levels of tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN-gamma), and interleukin-6 (IL-6) were high in patients with active visceral leishmaniasis. The proportion of both helper and suppressor CD4+ cells and of cells with NK and cytotoxic T phenotypes were depressed. Successful chemotherapy normalized these parameters with the exception of activated monocytes. Thus, the impaired cell-mediated immunity in human Leishmania donovani infection is primarily due to a decrease in the proportion and possibly the activity of helper CD4+ cells, while suppressor cells do not seem to play a relevant role. TNF alpha, IL-6, and IFN-gamma may prove to be useful markers for monitoring response to therapy.
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PMID:Mononuclear cell subpopulations and cytokine levels in human visceral leishmaniasis before and after chemotherapy. 837 45

The non-obese diabetic (NOD) mouse is a spontaneous model of human insulin-dependent diabetes mellitus. Both CD4+ and CD8+ T cells infiltrate the pancreatic islets of NOD mice prior to beta-cell destruction. T-cell lines isolated from the islets of NOD mice are tools for studying the pathogenesis of insulin-dependent diabetes mellitus. During attempts to generate such lines we isolated an autoreactive CD4+ T-cell line, designated C2, from the 'insulitis' lesion of a 20-week-old female non-diabetic NOD/WEHI mouse. Islet T cells were propagated by the addition of interleukin-2 and reexposure every 2 weeks to whole NOD islets and irradiated NOD spleen cells as antigen presenting cells. C2 cells proliferated up to 100-fold upon exposure to NOD antigen presenting cells but did not respond to whole NOD islets or antigen presenting cells from allogeneic mouse strains. Proliferation of C2 cells to NOD antigen presenting cells was blocked by a monoclonal antibody against the unique class II MHC molecule of NOD, I-Ag7. In response to NOD antigen presenting cells, C2 cells secreted interferon-gamma, tumour necrosis factor-alpha and interleukin-6 but no detectable interleukin-2, interleukin-4 or interleukin-10, a pattern of cytokine secretion more characteristic of Th1 CD4 cells. C2 cells displayed significant cytotoxicity in a redirected lysis assay. To explore a possible role for autoreactive T cells in the pathogenesis of autoimmune diabetes, C2 cells were injected i.v. into female NOD mice that had received cyclophosphamide to accelerate development of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Suppression of diabetes mellitus in the non-obese diabetic (NOD) mouse by an autoreactive (anti-I-Ag7) islet-derived CD4+ T-cell line. 840 38

The trophoblast, an epithelial cell of fetal origin that forms the physical barrier between the mother and developing conceptus, becomes a component of the host immune system during pregnancy. Of the classical immune cells, it most closely resembles the macrophage, also present in high numbers in the pregnant uterus. The macrophage and trophoblast, as cell classes, share characteristics such as phagocytosis, syncytialization, invasiveness, expression of the proteins CD4, CD14, IgG receptor (FcR), non-specific esterase, granulocyte macrophage-CSF (GM-CSF), colony stimulating factor 1 (CSF-1), interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor (TNF-alpha), transforming growth factors (TGF), platelet-alpha derived growth factor (PDGF) and receptors for these cytokines. In the uterus both cell types appear regulated by a common element, the uterine epithelium, that secretes cytokines such as CSF-1, GM-CSF, TNF alpha, TGF beta, IL-6, and leukaemia inhibitory factor (LIF) that target both macrophages and trophoblasts. The common characteristics and regulation that make teleological sense in terms of co-ordinating local uterine immunity during pregnancy may also be important in transmission of congenital diseases such as AIDS. The production by the uterine epithelium of a number of cytokines previously only associated with mononuclear phagocyte production and function predicts the existence of a similar, but broader, shared cytokine network encompassing trophoblast and the principal immune regulatory cell, the T lymphocyte.
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PMID:The trophoblast as an integral component of a macrophage-cytokine network. 843 11

In vivo induction of cytokines by a monoclonal antibody (mAb) against T-cell receptor (TCR) alpha beta and the protective effect induced by the mAb on a lethal infection with Listeria monocytogenes were studied. Injection of anti-TCR alpha beta mAb induced rapid production of endogenous tumour necrosis factor in the spleens, and gamma interferon and interleukin-6 in the blood streams and spleens of mice. Administration of anti-CD4 mAb, anti-CD8 mAb, or anti-Thy1.2 mAb resulted in suppression of anti-TCR alpha beta mAb-induced endogenous cytokine production. Mice were protected against lethal L. monocytogenes infection when treated with anti-TCR alpha beta mAb. The protective effect was not demonstrated in CD4+ cell- or CD8+ cell-depleted mice. These results suggest that anti-TCR alpha beta mAb shows a protective effect on a lethal infection with L. monocytogenes in mice and that the mAb-induced endogenous cytokines might be involved in the effect of anti-TCR alpha beta mAb.
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PMID:A monoclonal antibody against T-cell receptor alpha beta induces endogenous cytokines and prevents mice from a lethal infection with Listeria monocytogenes. 854 10

Earlier studies on propofol have shown increased percentages of T helper cells after minor surgery. In this study, the effects of propofol infusion anaesthesia on the immune response were compared with those of combined isoflurane anaesthesia in 30 patients (median age 47 years, ASA 1-2) undergoing major surgery. The total dose of propofol in the propofol infusion group of 15 women was 860 mg (range 540-1520 mg) and the median end-expiratory isoflurane concentration in the combined isoflurane group of 15 women was 0.6% (range 0.5-0.8). The following were measured; leucocyte and differential counts; percentages of lymphocyte subpopulations (CD3, CD4, CD8, CD19, CD16 and HLA-DR+CD3); phytohaemagglutinin-, concanavalin A-, and pokeweed mitogen-induced and unstimulated lymphocyte proliferation; plasma interleukin-6; serum group II phospholipase A2, C-reactive protein and cortisol concentrations. Measurements were made pre-operatively, at the end of the operation and on the first and fifth postoperative days. No statistically significant overall differences were observed in the immune response between the groups. The serum cortisol response was weaker in the propofol group than in the isoflurane group (p < 0.05). Time-related changes were seen within the groups.
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PMID:The influence of anaesthetic technique upon the immune response to hysterectomy. A comparison of propofol infusion and isoflurane. 854 87

The production of mature monocytes/macrophages is regulated by a group of hematopoietic growth factors, or colony-stimulating factors (CSF). We investigated the in vitro effect of human hematopoietic growth factors on human blood monocyte/macrophage differentiation and proliferation in short- and long-term in vitro cultures. The addition of macrophage CSF, granulocyte-macrophage CSF, and granulocyte CSF and interleukin-6 and interleukin-3 growth factors to monocyte/macrophage cultures induced morphological changes in cultured cells, including enhancement of cell growth and the formation of multinucleated giant cells, spindle-like cells, and fibroblast-like cells. In addition, CD4 and HLA-DR antigen expression was down regulated by the addition of growth factors without a change in the expression of other surface antigens, including CD3, CD11B, CD14, CD15, NK H1, and B1. The proliferating cell nuclear antigen was not detected in growth factor-treated nonadherent monocytes/macrophages in long-term cultures. Bromodeoxyuridine was incorporated in the adherent monocytes/macrophages, and intense staining in the small rounded cells which occur above the adherent cells in these cultures was observed after a 72-h pulse, indicating that monocytes/macrophages are slowly dividing cells.
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PMID:Effect of hematopoietic growth factors on human blood monocytes/macrophages in in vitro culture. 855 11

Fourteen patients with multiple sclerosis were treated with the humanized monoclonal antibody CAMPATH-1H which targets the CD52 antigen present on all lymphocytes and some monocytes; four also received anti-CD4 antibody. Lymphopaenia developed rapidly and was sustained for at least 1 year. In 12 patients, the first infusion of antibody was characterized by significant exacerbation or re- awakening of pre-existing symptoms lasting several hours. These clinical effects of antibody treatment correlated with increased levels of circulating cytokines. Peak levels of tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma occurred at 2 h, whereas the rise in interleukin-6 (IL-6) was significantly delayed and peaked at 4 h after starting antibody treatment. There was a decline in CH50, indicating complement activation. The neurological symptoms could not be attributed directly to pyrexia and were not provoked (in one patient) by an artificial rise in temperature. In the remaining two patients, a single pre-treatment with intravenous methylprednisolone (500 mg) prevented both the transient increase in neurological symptoms and the cytokine release. Our results, involving 14 intensively studied patients treated with humanized monoclonal antibodies, suggested that soluble immune mediators contribute to symptom production in multiple sclerosis; the mechanism remains uncertain but, on the available evidence, we favour the interpretation that cytokines directly affect conduction through partially demyelinated pathways.
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PMID:Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis. 862 84

We previously showed that a purE mutant (delta purE201) of Brucella melitensis 16M is attenuated for growth in cultured human monocytes (E. S. Drazek, H. H. Houng, R. M. Crawford, T. L. Hadfield, D. L. Hoover, and R. L. Warren, Infect. Immun. 63:3297-3301, 1995). To determine if this strain is attenuated in animals, we compared the growth of the delta purE201 mutant with that of strain 16M in BALB/c mice. The number of bacteria in the spleen and spleen weight peaked for both strains between 1 and 2 weeks postinfection (p.i.), though the number of delta purE201 cells was significantly less than the number of 16M cells recovered from the spleens of infected mice. During the next 6 weeks, delta purE201 was essentially eliminated from infected mice (three of five mice sterile; < 100 CFU in two of live mice at 8 weeks p.i.), whereas bacteria persisted at a high level in the spleens of 16M-infected mice (about 106 CFU per spleen). The number of bacteria in the livers and lungs of mice infected with either strain paralleled those in the spleen. Mice infected with 16M had a strong inflammatory response, developing dramatic and prolonged splenomegaly (five to eight times normal spleen weight) and producing serum interleukin-6. In contrast, mice infected with delta purE201 developed only mild, transient splenomegaly at 1 week p.i. and produced no interleukin-6 in their serum. We further characterized the host response to infection by measuring changes in immune spleen cell populations by flow cytometry. CD4- and CD8-positive lymphocytes declined by I week in both experimental groups, while MAC-1-positive cells increased. T-cell subpopulations remained low or declined further, and MAC-1 cells increased to three times normal levels during 8 weeks of infection with 16M but returned to normal by 4 weeks after infection with delta purE201. These results document infectivity and attenuation of delta purE201 and suggest that it should be further evaluated as a potential vaccine.
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PMID:Deletion of purE attenuates Brucella melitensis infection in mice. 867 25


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