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)

Polyclonal B-cell activation is a characteristic feature of AIDS and of the AIDS-related complex. Since the immunoregulatory cytokine interleukin-6 (IL-6) plays a major role in inducing B-cell differentiation, we examined the effects of native human immunodeficiency virus type 1 envelope glycoproteins gp120 and gp160 on IL-6 induction. In this study, we have demonstrated that both gp120 and gp160 have the ability to induce IL-6 mRNA and biologically active IL-6 protein secretion in peripheral blood mononuclear cells in vitro. The envelope protein preparations had no detectable endotoxin as tested by the Limulus amebocyte lysate assay, and hence we can rule out the effect of contaminating endotoxin, which is a potent inducer of IL-6 in monocyte/macrophage cell cultures. In addition, we have shown that the envelope glycoproteins act directly on CD4(+)-cloned T cells to induce IL-6 production in the absence of monocytes. These findings indicate that monocytes and T cells both contribute to the secretion of IL-6, which plays an important role in the pathogenesis of B-cell activation in human immunodeficiency virus infection.
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PMID:Human immunodeficiency virus type 1 envelope glycoproteins gp120 and gp160 induce interleukin-6 production in CD4+ T-cell clones. 165 94

Cytomedical therapy for human interleukin-6 transgenic mice (hIL-6 Tgm) was implemented by the intraperitoneal injection of alginate-poly(L)lysine-alginate (APA) membranes microencapsulating SK2 hybridoma cells (APA-SK2 cells) which secrete anti-hIL-6 monoclonal antibodies (SK2 mAb). IgG1 plasmacytosis in the hIL-6 Tgm was suppressed by a single injection of APA-SK2 cells, and the survival time of these mice was remarkably prolonged. The viable cell number and the SK2 mAb-secretion of APA-SK2 cells increased for at least one month both under culture conditions and in allogeneic recipients (in vivo). Moreover, SK2 mAb which were secreted from APA-SK2 cells injected into allogeneic recipients was detected in serum at high concentrations; 3-5 mg/ml from day 14 to day 50 post-injection. In contrast, the injection of free SK2 cells had no therapeutic effect on hIL-6 Tgm. These results strongly suggest that APA membranes microencapsulating cells which were modified to secrete molecules useful for the treatment of a disorder were effective as an in vivo long-term delivery system of bioactive molecules, as 'cytomedicine'.
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PMID:Cytomedical therapy for IgG1 plasmacytosis in human interleukin-6 transgenic mice using hybridoma cells microencapsulated in alginate-poly(L)lysine-alginate membrane. 906 Oct 40

To improve the safety of recombinant vaccinia virus vaccines, modified vaccinia virus Ankara (MVA) has been employed, because it has a replication defect in most mammalian cells. Here we apply MVA to human immunodeficiency virus type 1 (HIV-1) vaccine development by incorporating the envelope protein gp160 of HIV-1 primary isolate strain 89.6 (MVA 89.6) and use it to induce mucosal cytotoxic-T-lymphocyte (CTL) immunity. In initial studies to define a dominant CTL epitope for HIV-1 89.6 gp160, we mapped the epitope to a sequence, IGPGRAFYAR (from the V3 loop), homologous to that recognized by HIV MN loop-specific CTL and showed that HIV-1 MN-specific CTLs cross-reactively recognize the corresponding epitope from strain 89.6 presented by H-2Dd. Having defined the CTL specificity, we immunized BALB/c mice intrarectally with recombinant MVA 89.6. A single mucosal immunization with MVA 89.6 was able to elicit long-lasting antigen-specific mucosal (Peyer's patch and lamina propria) and systemic (spleen) CTL responses as effective as or more effective than those of a replication-competent vaccinia virus expressing 89.6 gp160. Immunization with MVA 89.6 led to (i) the loading of antigen-presenting cells in vivo, as measured by the ex vivo active presentation of the P18-89.6 peptide to an antigen-specific CTL line, and (ii) the significant production of the proinflammatory cytokines (interleukin-6 and tumor necrosis factor alpha) in the mucosal sites. These results indicate that nonreplicating recombinant MVA may be at least as effective for mucosal immunization as replicating recombinant vaccinia virus.
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PMID:Induction of a mucosal cytotoxic T-lymphocyte response by intrarectal immunization with a replication-deficient recombinant vaccinia virus expressing human immunodeficiency virus 89.6 envelope protein. 973 70

We previously reported that SK2 hybridoma cells that secreted anti-human interleukin-6 (hIL-6) monoclonal antibodies (SK2 mAb) were microencapsulated within alginate-poly(L)lysine-alginate (APA) membranes (APA-SK2 cells) for immunoisolation, and a single intraperitoneal injection of these APA-SK2 cells remarkably improved IgG1 plasmacytosis in hIL-6 transgenic mice (hIL-6 Tgm). However, the duration of the effectiveness of APA-SK2 cells as a cytomedicine was unfortunately limited. In this study, we attempted to re-inject APA-SK2 cells into hIL-6 Tgm for the purpose of prolonging the cytomedical therapy. In hIL-6 Tgm re-injected with APA-SK2 cells, the plasma IgG1 level did not show any increase in 37 week old mice, and their survival time was at least three times longer than those of untreated hIL-6 Tgm. These results suggest that re-injected APA-SK2 cells survived and secreted SK2 mAb in the allogeneic mice. Thus, the limited duration of the cytomedical effects of APA-SK2 cells was probably caused by the disappearance of the inner space of microcapsules for cell proliferation, not by the rejection of the host's immune system. Therefore, if we can regulate the proliferation of the cells microencapsulated within a semipermeable membrane, we may be able to develop a cytomedicine which will continue its function longer after a single injection.
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PMID:Prolongation of the effective duration of cytomedical therapy by re-injecting SK2 hybridoma cells microencapsulated within alginate-poly(L)lysine-alginate membranes into human interleukin-6 transgenic mice. 1022 Feb 87

The abnormal vascular system of brain cancers inappropriately expresses membrane proteins, including proteolytic enzymes, ultimately resulting in blood extravasation. The production of inflammatory mediators, such as cytokines and nitric oxide, and tumor hypoxia have been implicated in these effects. We have previously shown that the activity of aminopeptidase A is increased in the abnormal vascular system of human and rat brain tumors. To study the mechanisms regulating the activities of peptidases in cerebral vasculature in brain tumors, we have developed a three-dimensional model of differentiated rat brain cells in aggregate cultures in which rat brain microvessels were incorporated. The secretion of interleukin-6 (IL-6) in the culture medium of aggregates was used as an indicator of inflammatory activation. Addition to these aggregates of C6 glioma cell medium (C6-CM) conditioned under hypoxic or normoxic conditions or serum mimicked tumor-dependent hypoxia or conditions of dysfunction of brain tumor vasculature. Hypoxic and normoxic C6-CM, but not serum, regulated peptidase activity in aggregates, and in particular it increased the activity of aminopeptidase A determined using histoenzymography. Serum, but not C6-CM, increased IL-6 production, but did not increase aminopeptidase A activity in aggregates. Thus soluble glioma-derived factors, but not serum-derived factors, induce dysfunctions of cerebral vasculature by directly regulating the activity of peptidases, not involving inflammatory activation. Tumor hypoxia is not necessary to modulate peptidase activity.
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PMID:Regulation of peptidase activity in a three-dimensional aggregate model of brain tumor vasculature. 1248 84

The characteristics of the microcapsule surface, which interacts directly with the host macrophages, may have a role in the biocompatibility of alginate-poly-L-lysine (PLL)-alginate (APA) microcapsule. The objectives of the study were: 1) to develop and validate a simple, rapid, and sensitive in vitro method for assessing microcapsule biocompatibility, based on microcapsule coincubation with macrophages and measurement, by reverse transcriptase-polymerase chain reaction, of cytokine mRNA expression, and 2) to evaluate the effect of alginate purification and PLL coating on macrophage activation. The mRNA expression of tumor necrosis factor-alpha and interleukin-1beta was significantly higher when macrophages were coincubated with beads made with nonpurified compared with purified alginate (p<0.01, p<0.05, respectively) and negative control (p<0.001) or with APA microcapsules compared with non-PLL-coated alginate beads and negative control (p<0.001). The mRNA expression of interleukin-6 differed significantly only when APA microcapsules were compared with a negative control (p<0.05). These results confirm that alginate purification improves microcapsule biocompatibility, and suggest that PLL is not completely covered and/or neutralized by the second alginate incubation and thus has a role in the host macrophage activation. The assay is sensitive to both alginate contaminants and microcapsule surface characteristics and may be a useful tool for the development of biocompatible microcapsules.
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PMID:Effect of poly-L-lysine coating on macrophage activation by alginate-based microcapsules: assessment using a new in vitro method. 1566 81

Prior research has demonstrated that the daily experience of negative affect is associated with increased levels of proinflammatory activity as evidenced by higher interleukin-6 among Americans but not among Japanese. This cultural difference may be driven by culturally divergent beliefs about negative affect as a source of threat to self-image versus as natural and integral to life. Here, we examined whether culture may moderate the relationship between negative affect and biological stress responses, with a focus on the hypothalamic-pituitary-adrenal (HPA) axis activity. By using culturally matched surveys of Americans (N = 761) and Japanese (N = 328), we found that negative affect was associated with a flattening of the diurnal cortisol slope among Americans after controlling for demographic variables, personality traits, sleep patterns, and health behaviors. In contrast, the association between negative affect and the HPA axis activity was negligible among Japanese. Moreover, we assessed biological health risk with biomarkers of both inflammation (interleukin-6 and C-reactive protein levels) and cardiovascular function (higher systolic blood pressure and total-to-HDL cholesterol ratio) and found that the relationship between negative affect and increased biological health risk, which was observed only among Americans, was mediated by the flattening of the diurnal cortisol rhythm. These findings suggest that cultural differences in how emotions are construed may make the experience of negative affect more or less stressful and differentially consequential for health. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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PMID:Feeling bad is not always unhealthy: Culture moderates the link between negative affect and diurnal cortisol profiles. 3100 20

The discrete emotion theory of affective aging postulates that anger, but not sadness, becomes increasingly maladaptive during older adulthood in predicting health-relevant physiological processes and chronic disease (Kunzmann & Wrosch, 2018). However, it is largely unknown whether different negative emotions have distinct functional consequences in the development of older adults' physical disease. To start examining this possibility, we investigated whether older adults' daily experiences of anger and sadness were differentially associated with two biomarkers of chronic low-grade inflammation (interleukin-6 [IL-6] and C-reactive protein [CRP]) and the number of chronic illnesses (e.g., heart disease, cancer, etc.). In addition, we examined whether such divergent associations would become paramount in advanced, as compared with early, old age. A community-dwelling study of 226 older adults (age 59 to 93; M = 74.99, SD = 7.70) assessed participants' anger and sadness over 1 week, inflammatory processes, number of chronic illnesses, and relevant covariates. Regression analysis showed that anger predicted higher levels of IL-6 and chronic illness in advanced, but not in early, old age. The age effect of anger on chronic illness was mediated by increased IL-6 levels. Sadness exerted a reversed, but nonsignificant, association with IL-6 and chronic illness, independent of age. No emotion or age effects were obtained for CRP. The study's findings inform theories of health, emotion, and life span development by pointing to the age-related importance of discrete negative emotions in predicting a major physiological pathway to physical health across older adulthood. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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PMID:Is anger, but not sadness, associated with chronic inflammation and illness in older adulthood? 3107 Mar 99