UNIPROT:P05231 - FACTA Search

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)

Cryptococcosis is an hematogenously disseminated meningoencephalitis during which the relationship between the disease severity and the immune response remains unclear. We thus analyzed, by enzyme-linked immunosorbent assay, proinflammatory (tumor necrosis factor alpha [TNF-alpha] and interleukin-6 [IL-6]) and anti-inflammatory (IL-10) cytokine levels in plasma at the time of diagnosis in 51 AIDS patients with culture-proven cryptococcosis. We used a murine model to determine the correlation between cytokine levels and fungal burden in blood and tissues and the kinetics of the immune response and of the formation of cerebral lesions. In AIDS patients, plasma TNF-alpha and IL-10, but not IL-6, levels were significantly higher in the case of fungemia or disseminated infection than in their absence, whereas the presence of meningitis had no influence on these levels. In mice, none of these cytokines were detected within the first day after inoculation. Later on, TNF-alpha and IL-10, but not IL-6, levels in plasma correlated significantly with the fungal burden in the blood and spleen but not the brain. In the brain, cytokine levels were low compared to those in other compartments, and tissue lesions and a degree of infection similar to those observed in humans were seen, further suggesting the relevance of this experimental model. Thus, AIDS patients with cryptococcosis produce an immune response that reflects the dissemination but not the meningeal involvement. This murine model of disseminated cryptococcosis can be used to investigate the pathophysiology of cryptococcosis and new therapeutic approaches.
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PMID:Cytokine profiles of AIDS patients are similar to those of mice with disseminated Cryptococcus neoformans infection. 1056 43

Taurine chloramine (TauCl) is a major chloramine generated in activated neutrophils as a result of the reaction of highly toxic hypochlorous acid and taurine, the most abundant free amino acid in cytosol. In this study we have tested the influence of TauCl on the properties of murine dendritic cells (DC), the major cell population involved in the initiation of an adaptive immune response against pathogenic organisms. N418+, MHC II+, B7-2+ dendritic cells, generated from the mouse bone marrow cells cultured in the presence of granulocyte-macrophage colony-stimulating factor, were stimulated by interferon-gamma and lipopolysaccharide to produce nitric oxide, reactive oxygen species, interleukin-6 (IL-6), tumour necrosis factor-alpha, and IL-12, in the presence of different doses of TauCl. TauCl differently inhibited the generation of these inflammatory mediators in a dose-dependent manner. Furthermore, TauCl selectively modulated the ability of DC to induce the release IL-2 and IL-10 from T cells. These results suggest that neutrophil-derived mediators, such as TauCl, at a site of inflammation, may affect the functions of sentinel DC and macrophages, and play a role in maintaining the balance between the inflammatory response and the induction of an antigen-specific immune response.
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PMID:Regulation of murine dendritic cell functions in vitro by taurine chloramine, a major product of the neutrophil myeloperoxidase-halide system. 1058 96

Human interleukin-6 (hIL-6) acts as a growth factor in several human B lymphoid cancers. As human herpesvirus-8 (HHV-8) encodes for a viral IL-6 (vIL-6), the viral cytokine may be responsible for several manifestations of HHV-8-related disorders. Using an anti-hIL-6 mAb (B-E8) which does not recognize vIL-6, we investigated the involvement of the human cytokine in the proliferation of HHV-8-positive primary effusion lymphoma (PEL) cells. In vitro, 5/5 PEL cell lines produced hIL-6 (4 to 1,200 pg/ml). The EBV- HHV-8+ cell line (BCBL-1) was adapted to grow in SCID mice. hIL-6 was detected in the serum of mice with grafts, as well as human soluble CD138 (sCD138) and human IL-10 (hIL-10). The serum level of these mediators increased with tumor progression. The effect of treatment with the B-E8 mAb on the tumor progression and survival was evaluated. This treatment significantly slowed down the tumor development: on day 54, there were more mice with low levels of sCD138 and hIL-10 in the treated group than in controls (p = 0.03 and 0.02, respectively); treatment also delayed death (median date of death was day 65 for control mice and day 84 for anti-hIL-6 mAb-treated mice; p < 0.02). Thus, hIL-6 is expressed in addition to vIL-6 in HHV-8-positive malignant B lymphocytes, and the viral cytokine does not totally substitute for human IL-6 in promoting tumor progression.
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PMID:Human interleukin-6 is in vivo an autocrine growth factor for human herpesvirus-8-infected malignant B lymphocytes. 1058 16

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a well-known stimulus for the activation, differentiation and survival of monocytes (MO). Up to now most investigations focused on the short-term effects of GM-CSF. In this study we investigated the effects of GM-CSF on the long-term differentiation of human MO in the presence of serum. We found that MO-derived macrophages (Mphi) cultured with serum plus GM-CSF (GM-Mphi) were different from control Mphi (SER-Mphi) in terms of lipopolysaccharide (LPS)-stimulated cytokine release: GM-Mphi showed an increased tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production, especially at lower LPS concentrations, but the secretion of IL-10 was diminished. In addition, GM-Mphi secreted TNF-alpha but not IL-6 and IL-10, spontaneously. The spontaneous TNF-alpha production was not due to LPS contamination as it could not be blocked by anti-CD14 antibody. Flow cytometry revealed, however, that the receptor for LPS, CD14, was up-regulated on GM-Mphi and those Mphi released twice as much soluble CD14 into the supernatant as compared with SER-Mphi. The higher CD14 expression also resulted in an enhanced LPS-binding capacity of GM-Mphi. Furthermore, the LPS-response of GM-Mphi could only be blocked by about fourfold higher concentration of anti-CD14 antibody compared with SER-Mphi. In summary, GM-CSF promotes the generation of a pro-inflammatory type of Mphi in two different ways: first, the down-regulation of autocrine IL-10 production increases the release of cytokines such as IL-6 and TNF-alpha and second, the up-regulation of membrane and soluble CD14 expression leads to a higher sensitivity towards LPS-stimulation.
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PMID:Granulocyte-macrophage colony-stimulating factor modulates lipopolysaccharide (LPS)-binding and LPS-response of human macrophages: inverse regulation of tumour necrosis factor-alpha and interleukin-10. 1059 79

Cytokine induction by dialyzer membranes has been related to several acute and chronic side effects of hemodialysis treatment, among them being immune dysfunction and progressive atherosclerosis. Surface modification of cuprophane dialyzers with the antioxidant vitamin E is a new approach to enhance biocompatibility and improve cytokine levels, as well as immune function. Twenty-one patients undergoing treatment with hemophane (HE) dialyzers were enrolled onto a crossover study with a vitamin E-coated (VE) dialyzer or a synthetic polyamide (PA) dialyzer. In vitro assays of lymphocyte activation and measurements of cytokine induction were performed to evaluate biocompatibility. Four weeks of treatment with either VE or PA dialyzers enhanced in vitro proliferation of peripheral blood leukocytes in comparison to treatment with HE membranes used before study entry. Enhancement of lymphocyte function was independent of dialysis efficiency, which was kept constant during the study. In the interdialytic interval, preactivation of monocytes for the production of interleukin-6 (IL-6) did not differ between VE or PA dialysis. In contrast, the VE membrane reduced acute production of IL-6 during a dialysis treatment, whereas the PA membrane did not. Unlike IL-6, the regulatory cytokine IL-10 is not inhibited by either membrane. This is important because IL-10 is believed to have a beneficial effect on immune function in dialysis patients. The VE membrane, despite being based on a cuprophane backbone, is similar to the highly biocompatible PA dialyzer in terms of its effect on lymphocyte function, whereas it exerts an additional suppressive effect on the overproduction of proinflammatory cytokines.
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PMID:Prospective crossover trial of the influence of vitamin E-coated dialyzer membranes on T-cell activation and cytokine induction. 1062 May 50

Patients with chronic renal failure show an immunodeficiency characterized by frequent infectious complications and a low response to vaccinations. This is paralleled in vitro by a low T-cell proliferation on mitogenic stimuli because of an impaired costimulation by accessory cells. Furthermore, alterations of the cytokine profile are correlated with impaired immune function. The immune system is influenced by both uremia and renal replacement therapy. To evaluate the influence of hemodialysis on immune parameters, we studied patients before and after the initiation of chronic hemodialysis therapy. Fourteen patients with end-stage renal failure were tested before dialysis initiation and during the first 6 weeks of hemodialysis treatment. We determined the in vitro T-cell proliferation, as well as plasma levels of interleukin-6 (IL-6) and the release of IL-6 and IL-10 into culture supernatant poststimulation with lipopolysaccharide. After 6 weeks of intermittent hemodialysis, in vitro T-cell proliferation on stimulation improved significantly (stimulation index, 21.6 +/- 18.5 versus 58.1 +/- 45.5; P < 0.01). This improvement occurred regardless of whether synthetic dialyzers or cellulosic membranes were used for the initiation of dialysis. Plasma IL-6 levels, as well as IL-6 and IL-10 secretion, did not change during the study period. In patients with end-stage renal disease, the initiation of hemodialysis led to a significant improvement of in vitro T-cell proliferation. This effect may have a role for an improvement of immune function in vivo. The expected normalization of IL-6 and IL-10 production may be masked by cytokine induction through hemodialysis membranes.
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PMID:Initiation of hemodialysis treatment leads to improvement of T-cell activation in patients with end-stage renal disease. 1073 80

In schizophrenic patients, multiple immune abnormalities have been reported, including increased production of proinflammatory cytokines. There is some evidence that antipsychotic drugs may have immunosuppressive effects. The aim of this study was to examine the in-vitro effects of different concentrations of antipsychotic agents on cytokine production by human whole blood. We examined the effects of clozapine and haloperidol, 10(-4), 10(-6) and 10(-8)M, on the unstimulated and stimulated (lipopolysaccharide+phytohemagglutinin) production of interleukin-6 (IL-6), IL-10, interferon-gamma (IFNgamma), and the IL-1 receptor antagonist (IL-1RA). Clozapine, 10(-6) and 10(-8)M, and haloperidol, 10(-4), 10(-6), and 10(-8)M, significantly increased the unstimulated and stimulated production of IL-1RA. Clozapine 10(-6)M significantly increased the stimulated production of IFNgamma. Clozapine 10(-4)M significantly suppressed the unstimulated production of IL-6 and IL-1RA and the stimulated production of IL-6, IL-10, IFNgamma and IL-1RA. The results suggest that both clozapine and haloperidol, at concentrations within the therapeutic range, may exert immunosuppressive effects through an enhanced production of IL-1RA.
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PMID:Immunosuppressive effects of clozapine and haloperidol: enhanced production of the interleukin-1 receptor antagonist. 1074 53

Our objective was to evaluate the levels of interleukin-6 (IL-6), soluble receptors of IL-2 (sIL-2R), IL-10, and IL-1 receptor antagonists (IL-1ra) in the serum of patients with psoriatic arthritis (PsA) and to assess the correlation between these levels and parameters of clinical activity of skin and joint disease. In total, 34 patients with PsA and ten healthy volunteers participated in the study. Assessment of joint disease included duration of morning stiffness, number of tender and swollen joints, right and left grip, the presence of inflammatory spinal back pain, and Schober test. Current severity of skin disease was graded according to the psoriasis area and severity index (PASI). Erythrocyte sedimentation rate (ESR) was determined as a marker of disease activity. Serum levels of IL-6, sIL-2R, IL-1ra, and IL-10 were measured by an enzyme immunoassay kit. Significantly higher serum levels of IL-6, sIL-2R, IL-1ra, and IL-10 were found in patients with PsA in comparison with healthy volunteers. A statistically significant correlation was found between levels of sIL-2R and PASI, whereas no association was found with clinical parameters of joint severity. Levels of IL-lra correlated with the number of tender and swollen joints. No correlation was found between levels of IL-6, IL-10, and clinical parameters of skin and joint severity. In the group of patients with PsA, serum levels of sIL-2R clearly correlated with severity of skin disease, whereas levels of IL-1ra were associated with joint severity.
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PMID:Serum levels of IL-10, IL-6, IL-1ra, and sIL-2R in patients with psoriatic arthritis. 1077 88

Experimental studies have demonstrated that the route of nutritional supply impacts the systemic metabolic responses after surgical injury. Intestinal mucosal atrophy, as induced by total parenteral nutrition (TPN) or prolonged bowel rest, has been reported to enhance bowel endotoxin translocation. The operative procedure for thoracic esophageal cancer, including thoracotomy, laparotomy, and three-field lymph-node dissection, is a particularly stressful surgery that requires long-term aggressive nutritional support and often results in the postoperative hypermetabolic state, leading to perturbation of postoperative immune function. Interleukin-6 (IL-6) plays an important role in host inflammatory responses, whereas IL-10 is linked to suppression of cellular immunity. The aim of this study was to investigate how the antecedent nutritional routes influence systemic IL-6 and IL-10 responses and endotoxin translocation after an operation for thoracic esophageal cancer. Twenty-nine patients who underwent esophagectomy with three-field lymphadenectomy were investigated. They were assigned to groups receiving either TPN (n = 18) or enteral nutrition (EN; n = 11) providing 35 kcal x kg(-1) x d(-1) of energy and approximately 1.2-1.5 g x kg(-1) x d(-1) of amino acids. These nutritional supports were conducted from 1 wk before the operation to 14 d after the operation. Serum IL-6, IL-10, and endotoxin concentration were measured before and during the operation and at 2 h and 1, 3, and 7 d after the operation. IL-6 in sera was significantly higher after the operation in both groups. In the EN group, however, significantly less IL-6 production was observed on the third and seventh postoperative days when compared with those patients in the TPN group. Similarly, serum IL-10 concentration in the TPN group showed a significantly higher level than that in the EN group. Serum IL-6 showed a significant positive correlation with IL-10 at 2 h and at 7 d after the operation, suggesting that the reduced inflammatory responses were related to the inhibition of the development of postoperative immunosuppression. Endotoxin concentration in sera was significantly lower in the EN group after the operation than in the TPN group. Perioperative EN provides better regulation of inflammatory cytokine responses and may contribute less to immunosuppression after major surgery than parenteral nutrition. The attenuated production of endotoxin induced by EN may play an important role in these phenomena.
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PMID:Modulating effects of the feeding route on stress response and endotoxin translocation in severely stressed patients receiving thoracic esophagectomy. 1079 4

Studies have shown that cell-mediated immunity is markedly suppressed after thermal injury. T lymphocyte dysfunction and macrophage hyperactivity have been implicated as causative factors. Previous studies have primarily examined the effects of thermal injury on alphabeta T lymphocytes; however, the role of gammadelta T lymphocytes in the immune response after thermal injury is unclear. Therefore, wild-type mice and mice lacking the TCR delta gene (TCR delta-/-) were subjected to a third-degree scald burn and cell-mediated immune responses assessed at 7 days post-injury. TCR delta-/- mice had 75% mortality after burn injury compared with 25% mortality in the wild-type group. Plasma interleukin-6 (IL-6) levels were significantly elevated at 2, 4, and 18 h post-injury, whereas no difference was observed in tumor necrosis factor alpha (TNF-alpha) and prostaglandin E2 (PGE2) plasma levels. Plasma levels of these inflammatory mediators were similar in wild-type and TCR delta-/- mice post-injury. Splenic macrophage PGE2, IL-6, TNF-alpha, and IL-10 production was significantly increased in wild-type mice at 7 days post-injury, whereas macrophages from injured TCR delta-/- mice had a significantly attenuated capacity to produce IL-6 and TNF-alpha. In contrast, the increased release of PGE2 and IL-10 by macrophages post-injury was not reduced in TCR delta-/- mice. These results implicate a dual role for gammadelta T lymphocytes in the immunopathogenic response to burn injury: (1) they contribute to survival from the insult; and (2) they mediate the induction of a pro-inflammatory macrophage phenotype at 7 days post-injury. Thus, gammadelta T lymphocytes, in part through the modulation of macrophage activity, appear to contribute to the immune dysfunction after thermal injury.
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PMID:Insights into the role of gammadelta T lymphocytes in the immunopathogenic response to thermal injury. 1081 Oct 4

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