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 use of a highly sensitive method of in situ hybridization capable of detecting one copy of interferon (IFN) mRNA per cell coupled with quantitative analysis of cytokine mRNA showed that the number of copies of mRNA per cell was directly proportional to the logarithm of the number of silver grains formed over that cell. More than 90% of both virus-induced human Namalwa and mouse C243 cells exhibited grain counts significantly greater than background values following in situ hybridization with riboprobes complementary to human IFN- alpha and mouse IFN- beta mRNA, respectively. Labeling was shown to be specific, as the labeled probe was displaced by a 200-fold excess of the specific unlabeled probe but not by a 200-fold excess of an unrelated probe. Although the large majority of cells within a population responded to induction, considerable variation was observed, however, in the content of IFN mRNA per cell: 24% of induced C243 cells contained more than 50 copies of IFN-beta mRNA per cell while 60% of the cells contained 10 copies or less. Low levels of IFN mRNA were also detected in both uninduced C243 cells and uninduced Namalwa cells. Five to 10% of peripheral blood mononuclear cells from normal donors expressed INF-alpha mRNA following induction in vitro. Approximately 1% of untreated peripheral blood mononuclear cells also exhibited low levels of IFN-alpha mRNA. Analysis of interleukin-6 (IL-6) mRNA showed that 97% of TNF-induced human MG63 cells contained IL-6 mRNA, although, again, the amount varied considerably from cell to cell.
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PMID:Expression of the genes of class I interferons and interleukin-6 in individual cells. 186 61

In order to verify the participation of some cytokines in the expression of the suppressor activity of splenic macrophages (M phi s) induced by Mycobacterium avium complex (MAC) infection, we studied whether anticytokine antibodies were capable of blocking their suppressor activity against concanavalin A (ConA)-induced mitogenesis of splenocytes (SPCs). When either anti-tumor necrosis factor (TNF), anti-transforming growth factor-beta (TGF-beta), or anti-interferon-gamma (IFN-gamma) antibody was added to culture medium, suppressor activity was markedly reduced, in the order of anti-TNF, anti-IFN-gamma, and anti-TGF-beta antibodies. By contrast, neither anti-interleukin-6 (IL-6) nor anti-IL-10 antibody exerted such a blocking effect. Therefore, TNF, IFN-gamma, and TGF-beta seem to be related to the full display of the suppressor function of MAC-induced M phi s. However, TNF-alpha and IFN-gamma but not TGF-beta were substantially lacking in inhibitory action against SPC mitogenesis, when added exogenously. Hence, it is unlikely that TNF-alpha and INF-gamma directly modulated the proliferative response of T cells. On the other hand, both TNF-alpha and IFN-gamma potentiated the effector function of the suppressor M phi s. Because their suppressor activity was severely reduced by NG-monomethyl-L-arginine and aminoguanidine, nitric oxide (NO) synthase inhibitors, an NO-dependent mechanism is important for the expression of the immunosuppressive function of MAC-induced M phi s. Moreover, because these M phi s seem to produce a substantial amount of TNF-alpha in membrane-bound form, cell-to-cell contact might be needed for efficient expression of their suppressor action on target T cells.
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PMID:The role of tumor necrosis factor, interferon-gamma, transforming growth factor-beta, and nitric oxide in the expression of immunosuppressive functions of splenic macrophages induced by Mycobacterium avium complex infection. 749 69

A model of murine heterotopic allogeneic transplantation was used to study the rejection characteristics of three tissues--adult cornea, fetal pancreas, and fetal skin--for attributes that might explain their variation in rejection rates and help define the determinants of graft immunogenicity. Under identical conditions, tissues were transplanted to the renal subcapsular space and their base-line rejection rates compared. The expression of MHC class I and II and intercellular adhesion molecule-1 (ICAM-1), was determined for each tissue, as was their ability to produce interleukin-6, IL-3, interferon-gamma, and granulocyte-macrophage colony-stimulating factor in vitro. These studies were performed under basal conditions and after stimulation with concanavalin A-stimulated spleen cell supernatant (CAS) or INF gamma. Corneal grafts had a slow rejection rate compared with pancreas and skin. While all three tissues had low basal expression of MHC class II, both fetal skin and pancreas, but not adult cornea, were able to increase this under our experimental conditions. Pancreas and skin produced IL-6 under basal conditions and could be stimulated to increase production 2-3-fold but the cornea did not basally produce IL-6 and showed minimal upregulation. We postulate that delayed corneal rejection, compared with pancreas and skin, results from two compounding deficiencies: the relative lack of class II MHC-positive APC and the inability to overcome this deficiency by upregulating class II expression and producing accessory molecules for antigen presentation.
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PMID:A comparison of corneal, pancreas, and skin grafts in mice. A study of the determinants of tissue immunogenicity. 751 13

Recently, several lines of evidence have suggested the possible of immunological dysfunction in the pathogenesis of schizophrenia. We therefore investigated the ability to produce interferons and lymphokines in response to mitogenic or viral stimulation in a whole blood assay of 37 schizophrenic patients (DSM-III-R) and of 42 healthy blood donors. Phytohaemagglutinin (PHA) was used for the induction of interleukin-2 (IL-2), interferon gamma (INF gamma), interleukin-6 (IL-6) and the soluble interleukin-2 receptor (sIL-2R) and Newcastle Disease Virus (NDV) for the induction of interferon alpha 2 (INF alpha 2). All lymphokines and, in addition, the sIL-2R in the sera were determined by ELISA technique. The psychopathological status of the patients was assessed by psychiatrists according to internationally accepted standards. The patient group showed a trend to lower levels of the interferons alpha 2 and gamma and a significant decrease of IL-2 production. The sIL-2R levels were significantly increased in the sera of schizophrenic patients. The latter increase was associated with a poor assessment of prognosis (Strauss and Carpenter). This association appears to be of interest. However, its significance is not understood, since longitudinal studies could not be performed.
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PMID:Production of interferons and lymphokines in leukocyte cultures of patients with schizophrenia. 754 76

Cultured rat hepatocytes have been used to compare the relative activities of cytokines to inhibit the phenobarbital (PB) or 3-methylcholanthrene (MC) induction of cytochrome P4502B1 and 2B2 (P4502B1/2) or P4501A1 and 1A2 (P4501A1/2), respectively. Recombinant cytokines tested were human interleukin-6 (IL-6), interleukin-1 alpha and -beta (IL-1 alpha and IL-1 beta, respectively), and rat gamma-interferon (INF gamma). Hepatocytes were cultured in the presence of 2 mM PB or 1 microgram MC/mL culture medium for 24 hr with or without the cytokines. Benzyloxyresorufin and ethoxyresorufin O-dealkylase (BROD and EROD, respectively) activities were determined as indices of P4502B1/2 and P4501A1/2, respectively. All cytokines produced a concentration-dependent inhibition of the PB induction of BROD activity. IL-1 beta and IL-6 were approximately equipotent with IC50 values of 1-2 U/mL, causing greater than 90% inhibition of PB induction of BROD activity at a concentration of 50 U/mL culture medium. IL-1 alpha tended to be less active. PB induction of BROD activity was also inhibited by INF gamma, but higher concentrations (62.5 to 500 U/mL culture medium) were required. All cytokines were less effective in inhibiting the MC induction of EROD activity than the PB induction of BROD activity. IL-1 beta and IL-6, at 50 U/mL culture medium, inhibited EROD induction by only 35% compared with the greater than 90% inhibitory effect on the PB induction of BROD activity. INF gamma was ineffective in inhibiting EROD activity at the concentrations studied. Western immunoblot analysis indicated that the cytokines prevented the ability of the inducers to increase the expression of P4502B1/2 and P4501A1/2 immunoreactive proteins, and this effect correlated with their inhibitory effect on induction of enzyme activity. The results suggest that inducible isoforms of cytochrome P450 differ in their susceptibility to regulation by the cytokines, and that cytokines possess differential activity to inhibit the induction of P450 isoforms, with IL-1 beta and IL-6 being the most effective.
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PMID:Differential effect of cytokines on the phenobarbital or 3-methylcholanthrene induction of P450 mediated monooxygenase activity in cultured rat hepatocytes. 784 Jul 89

alpha-Melanocyte-stimulating hormone (alpha-MSH), a tridecapeptide derived from pro-opiomelanocortin, has potent antiinflammatory activity in laboratory animals. alpha-MSH inhibits nitric oxide production by murine macrophages, an influence believed to reflect activation of an autocrine circuit in these cells, one that is based on production and release of alpha-MSH and subsequent stimulation of melanocortin receptors. We found that THP-1 cells, human monocytic cells, produced alpha-MSH; this production was increased by interleukin-6, tumor necrosis factor a, or concanavalin A. These cells also expressed the gene for the human alpha-MSH receptor MC1. Unlike murine macrophages, THP-1 cells produced little nitrite in response to interferon-gamma (IFN-gamma) and lipopolysaccharide, and a-MSH inhibited this production only slightly. However, production of neopterin, a presumed primate homologue of nitric oxide in lower animals, was increased in THP-1 cells stimulated with INF-gamma plus TNF-alpha and alpha-MSH significantly inhibited this production. The evidence indicates that an autocrine regulatory circuit based on alpha-MSH occurs in human monocyte/macrophages much as in murine macrophages. alpha-MSH-induced modulation of specific inflammatory mediators/cytotoxic agents appears to differ depending on the importance of the mediators in the myelomonocytic cells of different species.
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PMID:alpha-MSH production, receptors, and influence on neopterin in a human monocyte/macrophage cell line. 860 97

High-dose methylprednisolone (HDMP, 20-30 mg/kg/day po) treatment has been shown to increase the number of bone marrow and peripheral blood CD34 positive progenitors and serum granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in patients with ALL and AML. To investigate the effect of HDMP on some other hematopoietic regulatory cytokines, tumor necrosis factor-alpha (TNF-alpha), gamma-interferon (gamma-INF), granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) were studied by microplate ELISA technique in 15 chemotherapy-induced neutropenic episodes of 14 children with acute leukemia (eight with ALL and six with AML) in whom HDMP was given alone (30 mg/kg/day po) for 4 days. The absolute neutrophil counts increased significantly in all neutropenic episodes on the fourth day of HDMP treatment. The TNF-alpha was 93.5 +/- 161 pg/ml in ALL and 78.3 +/- 61.4 pg/ml in AML before treatment and 76.1 +/- 160 pg/ml in ALL and 19.1 +/- 39.8 pg/ml in AML after treatment. The gamma-INF was 204.1 +/- 210.3 pg/ml in ALL and 130.8 +/- 138.3 pg/ml in AML before treatment and 28.6 +/- 50.5 pg/ml in ALL and 23.3 +/- 20.4 pg/ml in AML after treatment (P<0.05). Serum G-CSF and GM-CSF levels increased in all episodes (100%). The GM-CSF levels increased from 12.2 +/- 10.9 pg/ml to 36 +/- 24.7 pg/ml after treatment in ALL (P<0.05) and from 13.3 +/- 4 pg/ml to 45 +/- 48.1 pg/ml in AML (P<0.05). Serum G-CSF levels increased from 13.3 +/- 11.7 pg/ml to 83.3 +/- 86.8 pg/ml after treatment in ALL (P<0.05) and from 6.6 +/- 12.1 pg/ml to 28.3 +/- 11.3 pg/ml in AML (P<0.05). However, IL-6 levels were undetectable in all patients before and after therapy. These preliminary data suggest that short-course HDMP treatment could decrease serum TNF-alpha and gamma-INF and increase G-CSF and GM-CSF levels.
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PMID:Serum TNF-alpha, gamma-INF, G-CSF and GM-CSF levels in neutropenic children with acute leukemia treated with short-course, high-dose methylprednisolone. 863 22

Recent studies have emphasized the role of peritoneal mesothelial cell (PMC) in peritoneal immune defense mechanisms in continuous ambulatory peritoneal dialysis (CAPD). The aim of this study was to evaluate a possible relationship between peritoneal dialysis effluent (PDE), cytokine (Cy) levels, and PMC viability and their impact on peritonitis morbidity. Fifteen patients initiating CAPD for end-stage renal failure participated in the study. The following parameters were evaluated: (1) the levels of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-6 (IL-6), and interleukin-8 (IL-8) in PDE samples taken 7 days after initiating CAPD, at the end of the first, third, and sixth month of CAPD (determined by a solid phase enzyme amplified sensitivity immunoassay EASIA); (2) peritoneal mesothelial cell viability [determined by the release of lactate dehydrogenase (LDH) and by trypan blue extrusion test] by isolating and culturing peritoneal mesothelial cells at the moment of the placement of the peritoneal catheter and at the sixth month of CAPD; (3) peritonitis incidence during the 24 months after starting CAPD. At the first month of CAPD in all patients there was a slight increase in PDE IL-1 beta and TNF-alpha levels, while other Cy were almost undetectable. Time course studies showed that in 10 patients (Group I) there was a significant increase in PDE levels of IL-6, IL-8, and INF-gamma (p < 0.0005) in comparison to other Cy and a good PMC viability. In the other 5 patients (Group II) there were higher PDE levels of IL-1 beta and TNF-alpha (p < 0.0005). This was associated with a marked reduction in PMC viability determined by the release of LDH and by the trypan blue extrusion test. During the 24 months after starting CAPD, incidence of peritonitis was one episode per 24 patient-months in Group I and one episode per 9.2 patient-months in Group II. Our results show that from the beginning of CAPD there are distinct patterns of Cy in the PDE that correlate with a different PMC viability and peritonitis morbidity. Thus the analysis of the above-mentioned parameters may be useful in the early identification of the risk of peritonitis, thus allowing preventive measures.
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PMID:Peritoneal dialysis effluent, cytokine levels, and peritoneal mesothelial cell viability in CAPD: a possible relationship. 936 Jun 42

This study examines i) the activity of serum prolyl endopeptidase (PEP) and dipeptidlyl peptidase IV (DPP IV) in detoxified alcohol-dependent patients without liver disease versus normal controls, and ii) the relationships between serum DPP IV and PEP activity and the production of cytokines or cytokine receptors, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interferon-y (IFN-y), IL-1 receptor antagonist (IL-1RA), and IL-10, and granulocyte-macrophage colony stimulatory factor (GM-CSF). Alcohol-dependent patients had significantly lower serum PEP and DPP IV activity than normal controls. We found that 58.3% and 50.0% of the alcohol-dependent patients, respectively, had PEP and DPP IV activities, which were lower than the mean control values minus 2 SD. There were significant inverse correlations between lowered serum DPP IV and PEP activity and the increased production of IL-6, INF-gamma, IL-IRA, IL-10, and GM-CSF. These results show that lower serum DPP IV and PEP activity may be related to the pathophysiology of alcohol dependence.
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PMID:Lower activity of serum peptidases in abstinent alcohol-dependent patients. 989 30

The aim of the study was to identify serum markers able to differentiate bacterial and viral origin in acute diarrhoea. Interferon-alpha (INF-alpha), C-reactive protein (CRP) and interleukin-6 were determined on admission in the sera of 119 children aged between 1 mo and 14 y who were hospitalized for rotavirus (n = 60) or bacterial diarrhoea (Salmonella spp. 39 cases, Shigella spp. 15 cases, Campylobacter jejuni 5 cases). CRP concentration was >10 mg/l in 48.3% of children with viral gastroenteritis and 86.4% of children with bacterial gastroenteritis. IL6 concentration was >100 pg/ml in 11.7% and 26.3% of cases, respectively. INF-alpha was detected in 79.1% of children with rotavirus (sens 79%) and in 3.5% (spec 93%) with bacterial gastroenteritis. However the INF-alpha assay takes 48 h and pathogens are often identified from stools before interferon results are available. We found that serum markers are not discriminating enough to differentiate between viral and bacterial gastroenteritis in emergency cases.
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PMID:Interferon-alpha in viral and bacterial gastroenteritis: a comparison with C-reactive protein and interleukin-6. 1041 39


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