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)

The study was initiated as an in vitro approach to the situation existing during intravesical bacillus Calmette-Guerin (BCG) instillation in patients with superficial bladder cancer. Cytokine secretion of a human bladder carcinoma cell line T24 treated with BCG was investigated. A 24-h treatment of T24 cells with BCG resulted in a tenfold higher secretion of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) when compared with T24 cells treated with Escherichia coli, Streptococcus faecalis or a cell wall preparation of Nocardia rubra (N-CWS). No secretion of IL-1 beta and IL-2 was detected. Pre-exposing T24 cells to BCG for various periods of time indicated that a minimum exposure time of 0.5-1 h was required to upregulate IL-6 and TNF alpha production. Extending the BCG pre-exposure time to 2 and 3 h further increased the rate of cytokine production. No significant difference was found, however, between the rate of secretion initiated after a 2-h or 3-h pre-exposure period. The amounts of these cytokines secreted in the presence of BCG-conditioned medium did not differ significantly from the constitutively secreted amounts, excluding an effect of products possibly secreted by BCG on the upregulation of IL-6 and TNF alpha. In addition, upregulation of cytokine production appeared to be dependent on the concentration of BCG. The results suggest that cytokines may be produced by urothelial tumor cells after intravesical instillation in patients with superficial bladder cancer, which may play a role in the mode of action of BCG.
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PMID:Cytokine production by the human bladder carcinoma cell line T24 in the presence of bacillus Calmette-Guerin (BCG). 827 92

In order to induce acquired cellular resistance (ACR) to facultative intracellular bacterial pathogens, infection with live organisms is required. It is possible that different cytokine responses to live bacteria or their extracted antigens could account for their different abilities to induce ACR. Therefore, mice were infected with live attenuated Brucella abortus vaccine strain 19, and their ability to produce cytokines, both in vivo and in vitro, was investigated over 12 weeks of infection. This was compared with the response to injection of soluble brucella proteins (SBP). During infection, serum levels of interleukin-6 (IL-6) were markedly increased over a period of 4 weeks during the peak of infection. SBP plus adjuvant induced a transient increase in serum IL-6. IL-1 and tumour necrosis factor-alpha (TNF-alpha) remained undetectable in both instances. Spleen cells taken at intervals after infection and cultured with brucella antigens produced high titres of IL-6, IL-1 and TNF-alpha. Immunization with SBP was less efficient than live infection at inducing these cytokines. Of the characteristically T-cell-derived lymphokines, interferon-gamma (IFN-gamma) production rose 2 weeks after infection, peaking at 6 weeks, while IL-2 was not detected until 6 weeks post-infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was produced in substantial amounts, but IL-3 production was minimal. In contrast, spleen cells from mice immunized with SBP produced IL-2 but failed to produce IFN-gamma. The implications of these results for the induction of ACR are discussed.
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PMID:Cytokine production in the murine response to brucella infection or immunization with antigenic extracts. 828 19

Interleukin 6 (IL-6)/hybridoma growth factor (HGF) has been shown to be the requirement for growth of murine hybridomas in vivo or in vitro. In this paper, two kinds of conditioned media (CM) from the culture supernatants of a human fibroblast cell line CRL1506 and a cloned Epstein-Barr virus (EBV) transformed human lymphoblastoid cell line (LCL) N23 were found to have IL-6 activity by strongly promoting the growth, antibody secretion (increase of one- to three-fold), and cloning efficiencies of heterohybridomas secreting human monoclonal anti-hemorrhagic fever with renal syndrome virus antibodies and LCL. Since these CM contained no detectable IL-2, and IL-4 had no effects on the growth of the cell lines, IL-6 was considered to be the main active component of the CM responsible for promoting hybridoma growth. This effect was further confirmed by IL-6-dependent cell line 7TD1 bioassay (IL-6 activity in the CM ranging from 1,000 to 10,000 units/ml). Moreover, we successfully established four EBV-transformed lymphoblastoid cell lines at single-cell level by adding an equal volume of CRL1506-CM to 10% FCS-RPMI1640 in limiting dilution. Finally, it is worth noting that the sensitivity of the heterohybridomas to the two kinds of CM was not the same and was not consistent with that of their parental myeloma cell lines. Thus, it suggests that the CM might contain more than one factor, and the choice of proper conditioned media should be very useful for human monoclonal antibody production.
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PMID:The effects of hybridoma growth factor in conditioned media upon the growth, cloning, and antibody production of heterohybridoma cell lines. 843 56

Interleukin-6 (IL-6) is a late-acting differentiation factor for human B cells activated by polyclonal mitogens such as pokeweed mitogen (PWM) and Staphylococcus aureus Cowan strain I, but its role in specific antibody responses has not been established. We show here that IL-6 has no consistent effect on specific antibody responses by tonsillar mononuclear cells (TMC) stimulated with influenza virus. A blocking IL-6 antibody also had no effect on antibody production, suggesting that endogenous IL-6 production was not required. In control experiments, this antibody inhibited PWM-stimulated immunoglobulin secretion and proliferation of the IL-6-dependent B cell line B9. A requirement for IL-6 in responses of unfractionated TMC may have been disguised by the presence of T cells. To overcome this problem, we investigated the effect of IL-6 on specific antibody production by T-depleted B cells stimulated with antigen in the presence of IL-2, which is a T cell replacing factor (TRF) for human B cells. Specific antibody production was restored by IL-2, but not IL-6. Neither IL-6 nor anti-IL-6 antibody had any consistent effect on specific antibody production by purified B cells stimulated with antigen and TRF. These experiments show that IL-6 does not have a significant role in antigen (influenza virus)-specific antibody responses by human B lymphocytes.
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PMID:Interleukin 6 is not required for antigen-specific antibody responses by human B cells. 845 86

Hydroxychloroquine has several less well-known actions that may have clinical relevance in treating systemic lupus erythematosus (SLE). (1) Hydroxychloroquine has a possible anti-thrombotic action. It is a platelet inhibitor and appears to decrease the risk of thromboembolism in patients with anticardiolipin antibodies. (2) Hydroxychloroquine is associated with lower serum cholesterol and low-density lipoprotein levels compared to those present in patients who are taking corticosteroids but not antimalarials for SLE. (3) It may also decrease abnormal levels of cytokines. Interleukin-6 (IL-6), soluble CD8 and soluble IL-2 receptors (sIL-2R) are lower in patients taking antimalarials compared to those on corticosteroids alone or on neither medication. Serum levels of CD8 and sIL-2R decrease after 6 weeks of hydroxychloroquine treatment. These findings may help explain the favorable response of SLE patients treated with antimalarials.
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PMID:The relevance of antimalarial therapy with regard to thrombosis, hypercholesterolemia and cytokines in SLE. 848 65

CH925 is a novel cytokine of a fusion protein interleukin-6 (IL-6)/IL-2 exhibiting erythropoietin (Epo)-like effects in vivo and ex vivo, in addition to its enhanced effects compared to IL-2 and IL-6 reported by us previously, which indicates its potential clinical use. Our present study was undertaken to determine the Epo-like activity of CH925 in vivo. The reticulocyte response was observed in transfusion-induced polycythemic mice by using flow cytometry with pyronin Y staining. On day 2 after injection of CH925, the average number of reticulocytes was 2.11% in the group given 250 micrograms/kg/d and 1.01% for 100 micrograms/kg/d. The mean fluorescence intensity (MFI) also significantly increased. Longitudinal studies of CH925 were performed on days 2, 4, and 10, and reticulocyte counts increased up to a peak on day 4. Activity of CH925 (100 micrograms/kg/d) corresponds to 1 U of standard rhEpo in our study.
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PMID:Erythropoietin-like activity in vivo of the fusion protein rhIL-6/IL-2 (CH925). 853 93

Pycnogenol is a commercial mixture of bioflavonoids that exhibits antioxidative activity. The effects of dietary pycnogenol on immune dysfunction in normal mice as well as those fed ethanol or infected with the LP-BM5 murine retrovirus were determined. The ethanol consumption and retrovirus infection caused abnormalities in the function and/or structure of a broad array of cells involved in humoral and cellular immunity. Pycnogenol enhanced in vitro IL-2 production by mitogen-stimulated splenocytes if its production was suppressed in ethanol-fed or retrovirus-infected mice. Mitogenesis of splenocytes did not show a significant change in mice treated with pycnogenol. It reduced the elevated levels of interleukin-6 produced in vitro by cells from retrovirus infected mice and IL-10 secreted by spleen cells from mice consuming ethanol. Natural killer cell cytotoxicity was increased with pycnogenol treatment.
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PMID:Immunomodulation by pycnogenol in retrovirus-infected or ethanol-fed mice. 859 2

Directed migration of lymphocytes from blood into lymph nodes and organ-associated lymphatic tissue, also referred to as homing, is initiated by T-cell adhesion to specialized high endothelial cells of postcapillary vessels. Here, we demonstrate that selective signal transduction pathways specifically modulate the expression of the cutaneous lymphocyte antigen (CLA), the putative skin-homing receptor, during naive to memory transition of CD4+ T cells in vitro. The results show that the expression of CLA is strongly induced by activation via CD2 [T11.1 + T11.2 monoclonal antibodies (mAb)]. Addition of transforming growth factor-beta 1 (TGF-beta 1), interleukin-6 (IL-6), and, to a lesser extent, IL-2 further enhanced the generation of CLA+ T cells, whereas the induction of this antigen was markedly inhibited by IL-4. Periodic restimulation via CD2 and long-term culture of activated cells in the presence of IL-2 and TGF-beta 1 resulted in stable expression of CLA during a culture period of more than 100 days. In contrast, activation of naive CD4+ T cells via CD3, CD28 or by mitogens induced a rapid naive to memory phenotype transition but a much lower percentage of CLA+ T cells showing only weak expression of the antigen. Furthermore, activation of purified CD4+ memory T cells by CD2 strongly induced expression of activation-related antigens CD25 and HLA-DR, but failed to up-regulate CLA expression. Our results show that primary stimulation conditions highly modulate the development of skin-associated T cells and indicate a new functional role for costimulatory adhesion pathways in regulating the expression of molecules associated with T-cell homing.
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PMID:CD2-mediated stimulation of the naive CD4+ T-cell subset promotes the development of skin-associated cutaneous lymphocyte antigen-positive memory cells. 869 Apr 52

Human peripheral blood leukocytes (hPBL) are a rich source of natural leukocyte interferon (IFN-alpha) when treated with Sendai virus. Sendai virus treatment of hPBL will also result in significant production of several chemokines and cytokines such as macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, RANTES, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-8, in a time-dependent way. A significant amount of MCP-1 is constitutively produced in overnight culture of leukocytes. The most abundant cytokine is IFN-alpha, which is induced to its maximum level approximately 11-15 h after addition of Sendai virus. The amount of IFN-alpha induced at 15 h after Sendai virus treatment is more than 16-fold higher than those of MIP-1alpha, MIP-1beta, and RANTES. IFN-alpha is also induced more than 60-fold higher than TNF-alpha and IL-8. The amount of IL-6 induced is approximately 400-fold less than IFN-alpha. Limited amounts of other cytokines such as IL-1alpha, IL-1beta, macrophage colony-stimulating factor, TNF-beta, and IFN-gamma are also induced in Sendai virus-treated hPBL. No measurable amount of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, leukemia inhibitory factor, IL-2, IL-3, IL-4, IL-5, IL-7, IL-10, IL-11, or IL-12 was induced in the supernatant of Sendai virus-treated hPBL.
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PMID:Cytokines induced by Sendai virus in human peripheral blood leukocytes. 869 16

The modulation of cytokine release induced by pentoxifylline (PTX) has recently been demonstrated not to be restricted solely to tumor necrosis factor (TNF)-alpha. This prompted us to study the influence of PTX on a larger spectrum of cytokines with proinflammatory actions [TNF-alpha, interleukin-6, (IL)-6, IL-1 beta, IL-8] or with implied actions in the TH1 (IL-2, IFN-gamma)/TH2 (IL-10) balance. The IL-1RA was also explored. This work was performed using a whole-blood model in which cytokine production is measured after stimulation by lipopolysaccharide (LPS) (25 micrograms/ml) and phytohemagglutinin (PHA) (5 micrograms/ml) in 1:10 diluted whole blood. The stimulation test was performed in blood from healthy controls and from septic patients (without septic shock) in the presence or absence of PTX at 10(-6), 10(-5), 10(-4), or 10(-3) M. In controls and septic patients, at a 10(-4) M PTX concentration the production of IL-2 is strongly diminished (26-32% of the basal level), followed by diminution of IFN-gamma (30-40%). As expected, of the proinflammatory cytokines TNF was the most strongly suppressed (50% of baseline) followed by IL-1 (about 80% of basal production). Finally, IL-10 was also influenced by PTX (65% of baseline). At 10(-4) M, IL-1RA and IL-6 were unaffected by PTX. Taken altogether, our data demonstrate that PTX possesses a much broader spectrum of activity on cytokine production than was initially described, and it appears to be a potential and promising immunotherapeutic agent.
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PMID:Production of proinflammatory cytokines and cytokines involved in the TH1/TH2 balance is modulated by pentoxifylline. 869 68


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