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)

Cells of the macrophage lineage are considered to be of special importance in the defense of the host against tumor development and spread. Immunotherapeutic strategies to stimulate macrophage (MAC) tumor cytotoxicity make use of activating compounds such as gamma-interferon which are given systemically. However, there are several lines of evidence that in malignant disease the generation of cytotoxic effector MACs is impaired. Both defective cell maturation and loss of responsiveness to activation are described. Here, a first clinical phase I trial of adoptive immunotherapy in cancer patients using autologous MACs generated in vitro from blood monocytes (MOs) is reported. Mononuclear cells were isolated by cytapheresis and density centrifugation and cultured in hydrophobic Teflon bags for 7 days with 2% autologous serum and recombinant human gamma-interferon being present for the last 18 h. Cytotoxic MO-derived MACs were then purified by countercurrent elutriation and reinfused into the patient. A total of 72 therapies have been performed with patients being treated i.v. (n = 8) and i.p. (n = 7). In vitro generated MACs proved to be mature as judged by the expression of maturation-associated surface molecules (MAX antigens, CD16, CD51, CD71), were cytotoxic to U937 tumor cells, and were efficient secretory cells. Cell dose escalation was performed in the first patients beginning with 10(8) MACs to finally infuse the total number of cells recovered from one single cycle of isolation and culture. MAC yield varied from 1 to 17 x 10(8) representing 13-79% of MOs initially seeded. Adoptive MAc transfer was well tolerated. Side effects observed were low-grade fever (less than 38.5 degrees C), induction of the coagulation cascade, and abdominal discomfort after i.p. application. The procoagulant activity of MAC autografts was cell dose dependent and demonstrated by detection of circulating fibrin monomers and thrombin-antithrombin complexes. Biological responses observed included elevated serum neopterin levels and the appearance of interleukin-6 in sera and ascitic fluids. Indication of a possible therapeutic effect was only observed in i.p.-treated patients and consisted of disappearance of malignant ascites in 2 of 7 patients.
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PMID:Adoptive transfer of tumor cytotoxic macrophages generated in vitro from circulating blood monocytes: a new approach to cancer immunotherapy. 170 43

The effect of various recombinant cytokines on the induction of interleukin-6 (IL-6) synthesis induced in adherent and nonadherent cells of human peripheral blood mononuclear cells (PBMNC) by bacterial lipopolysaccharide (LPS) or concanavalin A (CA) was studied. The results showed that human interferon-(HuIFN)-alpha, -beta, and gamma at a concentration of 100-10,000 IU/ml enhanced the LPS-induced IL-6 production in the adherent cell fraction of PBMNC. However, in nonadherent cells, treatment with HuIFN-alpha or -beta inhibited the CA-stimulated IL-6 production in a dose-dependent manner. Recombinant (r) IL-2 enhanced the IL-6 production of the adherent cells, while rIL-1 alone in the absence of other inducer induced IL-6 production in the nonadherent cell fraction. Other cytokines such as the recombinant tumor necrosis factor-alpha (rTNF-alpha) or rIL-6 itself did not modulate IL-6 production in human PBMNC. TNF and the interleukins studied did not affect the Sendai virus-induced IFN production in the adherent cells. In contrast, the different IFNs exerted a significant priming effect.
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PMID:The effects of various cytokines on interleukin-6 and interferon-alpha synthesis in human peripheral blood mononuclear cells. 170 39

It has been demonstrated that the liver loses its capacity to metabolise and eliminate drugs during viral infection or during the operation of host defence mechanisms. This loss in drug metabolism is due to the loss of the cytochrome P-450 component of the mixed function oxidase (the enzyme system primarily responsible for the oxidation of drugs, carcinogens and certain classes of endogenous substances such as steroids, fatty acids and prostaglandins). At present we have identified interferon and factors such as interleukin-1, interleukin-6 and tumour necrosis factor, released from Kupffer cells, as major mediators of the loss. The depression that occurs during viral infection is mediated via the production of interferon. This action of interferon requires the synthesis of an intermediate/s yet to be identified. The molecular mechanism for the decrease in cytochrome P-450 mediated drug metabolism during episodes of viral infections is caused by an interferon-mediated loss in mRNA and subsequent cytochrome P-450 synthesis in the liver.
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PMID:Alteration of drug biotransformation by interferon and host defence mechanism. 170 43

In macrophages from inbred mice the magnitude of the interferon (IFN) response to Newcastle disease virus (NDV) infection is under genetic control of the locus If-1, with C57BL/6 carrying the 'high-producer' allele If-1h whereas BALB/c have the 'low-producer' allele If-1l. The IFN produced consists of 90% IFN-beta and there are 10-fold differences between macrophages from If-1h and If-1l mice. Recently, we observed that interleukin-6 (IL-6) is coinduced by NDV in macrophages and seems to be under the same genetic control. Noninduced macrophages have been shown to secrete low amounts of antiviral activity endogenously when cultured in the presence of the macrophage-colony-stimulating factor (M-CSF). Here, we report that the amount of this endogenous IFN varies between macrophages from different mouse strains. Macrophages from BALB/c were found to secrete 5-10 times more endogenous IFN compared to C57BL/6. The antiviral activity could be identified as IFN-beta. Interestingly, we observed that endogenous IFN specifically down-regulates NDV-induced IFN and IL-6 production. Preculture of BALB/c macrophages in M-CSF plus anti-IFN-beta to neutralize the biological effects of the endogenous IFN provoked a 30- to 50-fold increase in NDV-induced cytokine production, resulting in a nearly complete abrogation of the genetically determined difference since the same treatment only caused a 6-fold increase in C57BL/6 macrophages following NDV infection. This increase in cytokine gene expression was specific for NDV and marked by a strong additional activation of IFN-alpha genes. Addition of mouse recombinant IFN-alpha 4 to anti-IFN-beta-treated macrophages for 18 h prior to NDV infection down-regulated again IFN gene expression and reestablished the genetic differences between macrophages from If-1h and If-1l mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation by endogenous interferon of virus-induced cytokine gene expression in mouse macrophages. 171 14

Mice were infected intravenously with a sublethal dose of Listeria monocytogenes cells and then levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), and gamma interferon (IFN-gamma) in the bloodstreams, spleens, and livers were monitored. The maximum level of TNF was detected at 72 h in the spleens and livers, but TNF was never detected in the bloodstreams. IL-6 appeared in the bloodstreams and spleens and peaked at 48 h. The maximum level of IFN-gamma could be detected in all three specimens, and the highest titer was shown in the spleens. Endogenous TNF production was suppressed by in vivo administration of anti-CD4 monoclonal antibody (MAb) or anti-asialo GM1 antibody but not by anti-CD8 MAb, whereas none of these antibodies suppressed endogenous IL-6 production. Endogenous production of neither IL-6 nor IFN-gamma was inhibited in rabbit anti-recombinant mouse TNF-alpha antibody-treated mice. Similarly, production of TNF and IL-6 did not decrease in anti-mouse IFN-gamma MAb-treated animals, but TNF production was augmented in these animals. These results suggest that the these endogenous cytokines are produced by different mechanisms in L. monocytogenes infection.
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PMID:Endogenous tumor necrosis factor, interleukin-6, and gamma interferon levels during Listeria monocytogenes infection in mice. 173 Apr 85

We have used the reverse transcriptase-polymerase chain reaction technique to gain insight into the pathogenesis of encephalitis caused by Borna disease virus (BDV). RNA specific for BDV was first detected in the olfactory bulb of intranasally infected rats at 6 days postinfection (p.i.). At 14 days p.i., high levels of BDV RNA were found in all brain regions, and at 26 days p.i., BDV-specific RNA was also present in the eye, nasal mucosa, and facial skin. In the chronic phase of the disease, BDV RNA was identified in many peripheral organs but not in blood. Analysis of brain tissue for the presence of cytokine mRNAs revealed that the mRNA levels of interleukin-6 (IL-6), tumor necrosis factor alpha, and IL-1 alpha had increased sharply at 14 and 26 days p.i. These cytokine mRNAs reached maximum levels at the peak of inflammatory reactions and decreased drastically in the chronic phase of the disease. Although IL-2 mRNA was also found in normal brain, it was markedly increased in BDV-infected brain at 14 days p.i. Expression of gamma interferon (IFN-gamma) mRNA, which was not observed in normal rat brain, was detected at 14 days p.i. and reached a maximum level at 38 days p.i. IL-2 and IFN-gamma mRNA expression correlated with expression of CD4 and CD8 mRNAs, indicating that both CD4+ and CD8+ T lymphocytes are induced in the early stages of BDV infection. Since IFN-gamma and CD8 mRNA levels were still highly elevated in the chronic phase of Borna disease, it is likely that CD8+ T lymphocytes act to reduce inflammation and to ameliorate neurological signs during the chronic phase of infection.
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PMID:Kinetics of virus spread and changes in levels of several cytokine mRNAs in the brain after intranasal infection of rats with Borna disease virus. 173 Nov 17

A 58-year-old female was admitted to our hospital because of anemia in March 1987. Monoclonal protein (IgA, kappa) was detected and a diagnosis of multiple myeloma was made. Partial remission was obtained after VAD therapy with alpha-interferon. In December 1989, she was readmitted because of a pathological fracture of the left humerus. A white blood cell count was 4400/microliters with 30% myeloma cells and the urine protein (Bence Jones protein) was 26 g/day. Systemic chemotherapy was not effective. She developed pleural and pericardial effusions, bone mass, disturbance of consciousness and died of respiratory failure only 3 months after readmission. The pleural and pericardial fluids contained many myeloma cells. c-myc gene rearrangement was detected in myeloma cells obtained from the pleural fluid using c-myc exon1 and exon2 probes. The levels of interleukin-6 (IL-6) measured by ELISA was 107.4 pg/ml in serum, 56.2 pg/ml in pleural fluid and 780.0 pg/ml in pericardial fluid. Because of the lack of any overt infectious focus, the level of IL-6 appears to have been related to aggressive proliferation of myeloma cells. It was of interest that C-reactive protein, induced by IL-6, was a good marker reflecting disease activity.
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PMID:[A high serum level of interleukin-6 in a patient with aggressive multiple myeloma]. 175 53

Poly(rI:rC) and Ampligen were entrapped in liposomes that were covalently coupled to Protein A, permitting binding to antibodies specific for the major histocompatibility complex-encoded H2K molecule of L929 cells, or to control antibodies. Free and encapsulated polynucleotides were compared for their capacity to stimulate secretion of interferon (IFN) and interleukin-6 (IL-6) and to induce cellular toxicity on L929 cells pretreated with IFN-alpha/beta. Free and encapsulated poly(rI:rC) or Ampligen (poly(rI:rC12-rU] induced similar levels of secretion of IFN over a broad dose range. The activity of the liposome-encapsulated polynucleotides was dependent on its binding to an antibody that permitted cell association and internalization; the same liposomes were inactive in the presence of control antibodies. IL-6 secretion was induced by double-stranded (ds) RNA in a dose-dependent manner, with a significantly greater effect seen for targeted, liposome-encapsulated material. The marked toxicity of targeted poly(rI:rC), as compared to free poly(rI:rC), was confirmed. Encapsulated Ampligen was less toxic than encapsulated Poly(rI:rC).
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PMID:Free and liposome-encapsulated double-stranded RNAs as inducers of interferon, interleukin-6, and cellular toxicity. 177 64

The quest for methods to protect cells from the damaging effects of ionizing radiation led to the observation that cytokines, endogenously produced hormone-like polypeptides, are radioprotective. Interleukin-1 and tumor necrosis factor-alpha, given before irradiation, can protect mice from doses of radiation that would be fatal to untreated animals. At lower doses of radiation, the hemopoietic growth factors, interleukin-1, interleukin-4, interleukin-6, tumor necrosis factor-alpha, interferon, and leukemia inhibitory factor can promote recovery when administered after irradiation. Exposure to ionizing radiation selectively induces expression of some cytokines. Recent work suggests that certain cytokines may initiate autocrine/paracrine regulated recovery and repair pathways. Thus, the radioprotective and therapeutic effects of supplementary pharmacological doses of cytokines may act by amplifying innate defenses to ionizing radiation.
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PMID:Radioprotection with cytokines--learning from nature to cope with radiation damage. 176 Feb 47

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


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