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)

We recently reported that human recombinant interleukin-6 (hrIL-6) microinjected into the preoptic area (POA) of guinea pigs induced fever at high doses, suggesting that IL-6 may be another endogenous pyrogen. This study was undertaken to determine whether hrIL-6 affects the single-unit activity of thermosensitive and thermally insensitive neurons in hypothalamic tissue slices and whether indomethacin (Indo) or naloxone (Nal), a cyclooxygenase inhibitor and a mu-opioid receptor antagonist, respectively, influences the effects of hrIL-6 on those neurons. hrIL-6 (2 x 10(3)-8 x 10(3) U/ml) depressed the activity in 50 (83%) of 60 warm-sensitive (W) neurons and excited all 4 cold-sensitive (C) neurons found. It had no effect, however, on 14 (48%) of 29 thermally insensitive (I) neurons, albeit 7 and 8 I neurons decreased and increased their firing rates, respectively. Indo (0.05-1 mg/ml) blocked the effect of hrIL-6 on 22 of 24 W neurons and 2 C neurons tested. Nal(0.1-1 mg/ml) blocked or reduced the effect of hrIL-6 on 21 of 25 W neurons and 1 C neuron recorded. These drugs induced no neuronal response per se. Nal at 2-5 mg/ml, which increased the activity of four W neurons by itself, reversed their depressed response to hrIL-6. These results support the possibility that IL-6-induced fevers may be mediated through an effect on thermosensitive neurons in the POA and that opioids and prostaglandin E may both be involved in this process.
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PMID:Hypothalamic neuronal responses to interleukin-6 in tissue slices: effects of indomethacin and naloxone. 150 50

In this paper, we examined the contribution of the lymphokine interleukin-6 (IL-6) to the growth of four virulent strains of Mycobacterium avium and the nature of the binding moieties on the mycobacteria. First, we showed that human or mouse recombinant interleukin-6 are potent growth factors for four strains of virulent M. avium. This was shown to occur in tissue culture medium, which does not support maximal growth of M. avium. Bioactive IL-6 was required, inasmuch as heat-activating IL-6 or adding an antibody against IL-6 blocked this growth-enhancing ability. The rapid uptake of IL-6 by M. avium was indicated by the fact that the incubation of IL-6 with the four M. avium strains led to a rapid removal of the bioactivity from the culture medium and a rapid removal of radiolabeled IL-6. Scatchard analysis of receptor interaction showed that the M. avium strains had a single receptor species with a Kd of 50 nM and the number of receptor sites was approximately 15,000 bacterium. Blocking experiments showed that the binding of radiolabeled IL-6 was fully displaceable with cold IL-6, but not with other lymphokines. These data suggest that IL-6 may play an important role in the pathogenesis of M. avium infections, notably by promoting growth of M. avium, and that some virulent M. avium strains bind IL-6 in a specific manner.
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PMID:Interleukin-6 is used as a growth factor by virulent Mycobacterium avium: presence of specific receptors. 155 50

We have previously described YA2, a human T-cell clone that secretes B-cell differentiation factor (BCDF) but not B-cell growth factor (BCGF). The BCDFs secreted by YA2 and HTLV-I-transformed YA2 (TYA2) were functionally similar in their ability to stimulate Ig secretion by Staphylococcus aureus Cowan strain I-activated B cells and IgM secretion by SKW6.4 cells. In addition, they were biochemically similar with a MW of 30 kDa by high-performance liquid chromatography (HPLC) sieving, and a pI of 6.0-6.8 by isoelectric focusing. The BCDF activity was not blocked by antibodies to interleukin 2 and BCGF. BCDF was purified from TYA2 supernatant by sequential media protein immunoadsorption, flat bed isoelectric focusing, HPLC TSK 2000 sieving, and repeated immunoadsorption and was then iodinated. The iodinated material had functional BCDF activity and migrated to a single band at MW 30 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and at pI of 6.8 by polyacrylamide gel isoelectric focusing. 125I-BCDF purified in this manner bound specifically to a BCDF-responsive cell line and not to phytohemagglutinin-activated T cells. 125I binding to the BCDF-responsive cell line was competitively inhibitable by the addition of cold BCDF. Thus we have purified and characterized a factor with BCDF activity and demonstrated that this factor binds specifically to a BCDF-responsive cell line.
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PMID:Functional and biochemical characterization of B-cell differentiation factor (BCDF) produced by an HTLV-I-transformed human T-cell clone and demonstration of specific binding of the factor to a BCDF responsive cell line. 288 97

The proinflammatory cytokines have been implicated in mediating myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. We tested the hypothesis that cytokine levels are elevated after uncomplicated coronary artery bypass grafting and associated with episodes of postoperative myocardial ischemia and dysfunction. Coronary artery bypass grafting was performed under general anesthesia with moderate systemic hypothermia and cold-blood potassium cardioplegic solution. Tumor necrosis factor-alpha and interleukin-6 levels were determined by bioassays, and interleukin-8 levels were measured by a sandwich enzyme-linked immunosorbent assay. Myocardial function and ischemic episodes were assessed by intraoperative transesophageal echocardiography and perioperative 12-channel Holter monitoring. A total of 22 patients were studied, with no deaths or complications. Arterial tumor necrosis factor-alpha rose in a bimodal distribution, peaking at 2 and 18 to 24 hours after the operation (at 20.2 +/- 6.4 pg/ml, [mean +/- standard error of the mean]) and 5.8 +/- 1.6 pg/ml, respectively; before cardiopulmonary bypass: 0.90 +/- 0.20 pg/ml, p < 0.001 for both peaks) then progressively declined to levels before bypass. Arterial interleukin-6 was maximally elevated immediately on termination of cardiopulmonary bypass and peaked again 12 to 18 hours after cardiopulmonary bypass (at 7520 +/- 2439 pg/ml and 6216 +/- 1928 pg/ml, respectively; before bypass: 746 +/- 187 pg/ml, p < 0.0001 for both peaks). Arterial interleukin-8 levels were more variable but followed a similar pattern, peaking in the early period after cardiopulmonary bypass and again at 16 to 18 hours after the operation (at 4110 +/- 1403 pg/ml and 1760 +/- 1145 pg/ml, respectively; before bypass: 461 +/- 158, p < 0.05 for both peaks). By multivariate analysis, the aortic crossclamp time was independently predictive of postoperative cytokine levels. Left ventricular wall motion abnormalities were associated with both interleukin-6 and interleukin-8 levels, worsening scores being associated with increasing levels (for interleukin-6, p = 0.003; for interleukin-8, p = 0.05). Postoperative myocardial ischemic episodes were associated with interleukin-6 levels, six of seven (85%) patients with episodes of myocardial ischemia after a peak in interleukin-6 concentrations (p < 0.01). We conclude that proinflammatory cytokines are elevated after uncomplicated coronary revascularization and may contribute to postoperative myocardial ischemia and segmental wall motion abnormalities.
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PMID:Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. 793 95

Peripheral vasodilation is a common feature of warm heart surgery and creates clinical concerns when pressor agents become necessary because of the potential for some of these drugs to adversely affect flow through newly engrafted arterial and venous bypass conduits. The possible role of a temperature-dependent production of cytokines in the pathogenesis of this vasodilation was investigated in a two-part study. In part I, lipopolysaccharide-activated peritoneal rabbit macrophages (5 x 10(6)/ml) were incubated at 30 degrees or 37 degrees C up to 9 hours and the concentration of tumor necrosis factor released in the supernatant was serially measured by a bioassay. Tumor necrosis factor production was found to increase over time for each of the two temperatures of incubation but was significantly higher throughout the observation period in normothermic experiments than in those done at 30 degrees C. Part II was a prospective clinical study involving 30 patients who underwent either cold (core temperature 28 degrees to 30 degrees C, n = 15) or warm (37 degrees C, n = 15) cardiopulmonary bypass and in whom serum levels of tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 were measured by enzyme-linked immunosorbent assays at 2, 4, 10, and 24 hours after bypass. Cytokine levels were found to be consistently higher in patients having normothermic bypass. Differences between the two groups were significant 2 hours after bypass for tumor necrosis factor alpha and interleukin-6 (p < 0.02 and p = 0.0001, respectively) and 4 and 10 hours after bypass for interleukin-1 beta (p < 0.01 and p < 0.04, respectively). The incidence of vasodilation necessitating vasopressor support was twofold higher in the normothermic group (six patients versus three in the hypothermic group). Taken as a whole, patients supported by pressor agents had significantly higher cytokine levels after bypass than those who did not require pressor therapy. Our results suggest that vasodilation occurring with warm heart operation is, at least partly, mediated by a temperature-dependent release of cytokines. Vasodilation might therefore be mitigated by simply allowing the core temperature to drift during bypass. Our recent clinical experience suggests that this "tepid" heart surgery (32 degrees to 34 degrees C) effectively blunts most of the vasodilatory response to strictly normothermic bypass without compromising maintenance of myocardial aerobiosis during arrest.
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PMID:A potential mechanism of vasodilation after warm heart surgery. The temperature-dependent release of cytokines. 828

Interactions between influenza viruses and human macrophages were examined to detect potential mechanisms for enhanced febrile reactions previously associated with administration of an avian-human H1N1 reassortant vaccine. Cells exposed to that strain were compared with cells exposed to wild-type and cold-adapted H1H1 and H3H2 strains and an avian-human H3N2 strain. Cells exposed to the avian-human H1N1 virus showed increased synthesis of viral neuraminidase, previously reported to induce fever-producing cytokines, but no detectable increase in production of interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha measured by immunoassay, or decrease in interleukin-1 inhibitor activity by bioassay.
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PMID:Human macrophage responses to vaccine strains of influenza virus: synthesis of viral proteins, interleukin-1 beta, interleukin-6, tumour necrosis factor-alpha and interleukin-1 inhibitor. 842 35

The best-known activity of Staphylococcus aureus sphingomyelinase C, alias beta-toxin, is as a hemolysin that provokes hot-cold lysis of erythrocytes which contain substantial amounts of sphingomyelin in the plasma membrane. Sheep erythrocytes are most susceptible, and we found that one hemolytic unit, representing the toxin concentration that elicits 50% hemolysis of 2.5 X 10(8) erythrocytes per ml, corresponds to 0.05 enzyme units or to approximately 0.25 microg of sphingomyelinase per ml. The cytotoxic action of beta-toxin on nucleated cells has not been described in any detail before, and the present investigation was undertaken to fill this information gap. We now identify beta-toxin as a remarkably potent monocytocidal agent. At a concentration of 0.001 U/ml, corresponding to approximately 5 ng/ml, beta-toxin killed over 50% of human monocytes (10(6) cells per ml) within 60 min. By contrast, 1 to 5 microg of beta-toxin per ml had no cytocidal effects on human granulocytes, fibroblasts, lymphocytes, or erythrocytes. A selective monocytocidal action was also observed with sphingomyelinase C from Bacillus cereus and a Streptomyces sp., whereas phospholipase A2 and phospholipase D at 100 U/ml were without effect. Monocytes succumbing to the action of beta-toxin processed and released interleukin-1beta, soluble interleukin-6 receptor, and soluble CD14 into the supernatant. Thus, monocyte killing by beta-toxin is associated with cytokine-related events that are important for the initiation and progression of infectious disease. These findings uncover a potentially important role for sphingomyelinase as a determinant of microbial pathogenicity.
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PMID:Selective killing of human monocytes and cytokine release provoked by sphingomyelinase (beta-toxin) of Staphylococcus aureus. 875 23

Interleukin-6 is associated with poor prognosis in breast cancer. Expression of GP96, a glucose regulated stress protein, is related to drug resistance in tumor cells. Interleukin-6 has previously been shown to induce GP96 expression in a murine myeloblastic cell line. BT474 or MDA-MB231 cells were incubated with recombinant Interleukin-6 (100 to 750 U/ml) for 24 hr. To establish a time course for GP96 induction, MDA-MB231 cells were incubated with 250 U/ml recombinant interleukin-6 for 0-48 hr. Following incubation, cells were washed twice in phosphate-buffered saline (PBS) and cell lysates were prepared by adding 100 microliters of PBS and freezing at -20 degrees C. GP96 was assessed by immunoblotting. Breast tumor tissue and histologically normal breast tissue were obtained within 1 hr of resection and flash frozen in liquid nitrogen. Tissue was homogenized in ice-cold PBS and cell debris was pelleted by centrifugation at 300g at 4 degrees C for 5 min. Supernatants were collected and assayed for interleukin-6 by ELISA, and GP96 by immunoblotting. Both interleukin-6 (P < 0.001) and GP96 are elevated in breast tumor tissue compared to histologically normal tissue. Interleukin-6 (> or = 250 U/ml for > or = 12 hr) induces GP96 in the metastatic breast cancer cell line, MDA-MB231, but has no effect on GP96 levels in the primary cell line, BT474. Elevated interleukin-6 in breast tumors may induce GP96 expression in tumor cells conferring a survival advantage by rendering them resistant to cytotoxic therapy and other forms of stress.
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PMID:Interleukin-6 upregulates GP96 expression in breast cancer. 920 61

Autogenous hip marrow is an excellent source of pluripotential cells for regenerative procedures. However, before this treatment modality can be employed a method to attenuate osteoclast activity must be developed. The shock of cold storage (4 degrees C) is thought to abate osteoclast activity through the downregulation of osteolytic cytokines produced by osteoblasts. The objective of this study was to evaluate the effects of cold storage (4 degrees C) and endotoxin challenge on bone cell culture viability and interleukin-6 (IL-6) production. These cells (osteoblasts) were primarily harvested from murine calvaria utilizing sequential digestions, separated by density gradient and combined. Twelve-well cell culture plates were inoculated with 2 x 10(4) cells/ml and placed in cold storage for 1-14 d. After cold storage the cultures were then incubated at 37 degrees C for 1-20 d. A set of replicate plates was also challenged with 10 ng/ml endotoxin upon incubation at 37 degrees C for 4 consecutive days. Cells were evaluated daily for alkaline phosphatase activity. Cell culture supernatants were also collected daily and batch assayed for IL-6 production. Cell cultures did not survive more than 48 h of cold storage. There was a decrease in IL-6 secretion in all refrigerated cultures and a significant decrease in those cells refrigerated for 48 h versus control cultures (p < 0.05). Replicate cultures treated with endotoxin secreted significantly increased amounts of IL-6 in both the control cultures and the cultures exposed to 24 h of cold storage versus non-endotoxin-treated control cultures (p < 0.05). These observations suggest that after 48 h of cold storage autogenous marrow may be safe to use because of the dramatic decrease in IL-6 production by osteoblasts.
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PMID:The effects of cold storage and endotoxin challenge on osteoblast viability and interleukin-6 production. 965 76

The rat adrenal cortex produces the cytokines interleukin-6, tumor necrosis factor, interleukin-1beta, interleukin-1alpha, macrophage migration inhibitory factor, interferon-gamma inducing factor, and transforming growth factor-beta1. Interleukin-6, tumor necrosis factor, and macrophage migration inhibitory factor are localized to the zona glomerulosa. In contrast, interferon-gamma inducing factor is localized to the zona reticularis and fasciculata. Transforming growth factor-beta1 is localized to the zona fasciculata. Endotoxin and interleukin-1 increase interleukin-6 and tumor necrosis factor release from adrenal cells. In contrast, adrenocorticotrophic hormone, adenosine, serotonin, and dopamine increase adrenal interleukin-6 release, but inhibit tumor necrosis factor release. These secretagogues also increase interleukin-6 mRNA content of adrenal cells. Adrenocorticotrophic hormone decreases transforming growth factor beta1 content of adrenal glands. Endotoxin increases adrenal expression of mRNA for macrophage migration inhibitory factor, but decreases the tissue content of this protein. Endotoxin increases the expression of interleukin-1beta mRNA. Cold stress increases the expression of mRNA for interferon-gamma inducing factor. Therefore, cytokines are differentially expressed in the adrenal cortex and the release and production of these cytokines are regulated selectively. Because cytokines have effects on adrenal function and are differentially regulated, they may play autocrine/paracrine roles in regulating the adrenal gland.
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PMID:Cytokine expression in the rat adrenal cortex. 969 70


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