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)

Epstein-Barr virus (EBV)-induced in vitro infection of peripheral blood mononuclear cells (PBMCs) leads to a polyclonal proliferation and immortalisation of B lymphocytes. In the present study we determined the effects of three different cytokines, interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-6 (IL-6), and the tumour promoting phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on EBV-immortalised B lymphocytes. These factors have known activities on normal B cells. IL-4 and IL-6 increased significantly EBV-B cell proliferation after 3 and 5 days of culture, where IL-2 had no effect. The effect of IL-4 and IL-6 on EBV-B cells was abolished after pre-incubation with anti-IL-4 and anti-IL-6 neutralising antisera, respectively. TPA induced a dose dependent inhibition of proliferation both in serum free and 10% fetal calf serum (FCS) supplemented culture medium. Combinations of TPA and interleukins did not restore lymphoblastoid cell proliferation to background levels. All possible combinations of the three cytokines showed no synergistic or antagonistic effect on proliferation. TPA induced significant phenotypic changes of EBV immortalised B lymphocytes, by increasing IL-2 receptor (IL-2R) expression and decreasing CD20 and CD23 antigen expression. Other B cell differentiation antigens; HLA-DR, CD19, and transferrin receptor (CD71), did not demonstrate significant changes. A dose dependent inhibition of CD21 and increase in CD22 expression was observed in 2 out of 3 lymphoblastoid cell lines tested.
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PMID:Effects of phorbol esters and cytokines (interleukin-2,-4, and -6) on the proliferation and surface phenotype of Epstein-Barr virus immortalised human B lymphocytes. 133 96

Follicular dendritic cells (FDCs) form a dense network between B cells within the germinal center and are thought to be an important component of this B-cell microenvironment. Previous immunophenotypic studies have been inconclusive in determining the cellular origin of FDCs. Gene coexpression within individual and highly enriched FDCs was determined using polymerase chain reaction. FDCs contain a very restricted mRNA pattern with high levels of message for the C3d receptor (CR2, Epstein Barr-virus/EBV receptor, CD21) and lack of mRNA for CD20, CD45, CD4, fibronectin, and platelet-derived growth factor receptor alpha and beta. These observations are consistent with the hypothesis that FDCs may not be of classical hematopoietic or fibroblastic origin. The absence of interferon-gamma, tumor necrosis factor-alpha, interleukin-3, and interleukin-6 mRNA provides preliminary evidence that these cells might produce only a very restricted set of cytokines limited to the germinal center.
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PMID:Follicular dendritic cells contain a unique gene repertoire demonstrated by single-cell polymerase chain reaction. 182 82

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on cytokine profile was evaluated in a case of severe congenital neutropenia. The plasma levels of cytokines were measured before and during rhG-CSF therapy. These included G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha, interleukin-1 beta, interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4, interleukin-6 (IL-6), and tumor necrosis factor-alpha. Soluble interleukin-2 receptor (sIL-2R) was measured serially during rhG-CSF therapy. Lymphocyte subpopulations including CD2, CD3, CD4, CD8, CD19, CD20, and CD25 were also measured, rhG-CSF was administered once daily as a 30-min infusion. The patient was treated with increasing dose levels of 100, 200, 400, 800, and 1,600 micrograms/m2/day. The level of endogenous G-CSF was elevated to 334 pg/ml before treatment and GM-CSF, IL-2, IL-3, and IL-6 were slightly elevated. Clinically, he showed a moderate response to a high dose of rhG-CSF (1,600 micrograms/m2/day). Plasma levels of G-CSF markedly increased during therapy but plasma levels of other cytokines did not show significant changes during therapy and lymphocyte subpopulations did not significantly change. A drastic increase in sIL-2R expression was observed after rhG-CSF infusion and an increase in sIL-2R expression occurred even before a major increase in granulocyte counts. These results showed that a high dose rhG-CSF therapy may influence the cytokine network as judged by the increased sIL-2R expression.
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PMID:Cytokine profile during high-dose rhG-CSF therapy in severe congenital neutropenia. 750 1

Allogeneic blood transfusions have been associated with impaired outcome in surgical patients. This effect may be mediated by leukocytes. Animal experiments have shown that at least some of the effect can be modified by removal of leukocytes from transfused blood. Therefore, we compared the effects of autologous + leukocyte-depleted against standard allogeneic red blood cell transfusion on postoperative immunosuppression in 24 men undergoing coronary artery bypass surgery. In the autologous + leukocyte-depleted red blood cell transfusion group, patients received 800 +/- 200 mL (mean +/- SD) autologous blood and 2.2 +/- 2.0 units (mean +/- SD) of leukocyte-depleted saline-adenine-glucose-mannitol (SAGM) red blood cells. In the standard red blood cell transfusion group, patients were transfused with 5.5 +/- 1.4 units (mean +/- SD) of SAGM red blood cells. Leukocyte and differential counts; percentages of lymphocyte subpopulations (CD3-, CD4-, CD8-, CD16-, CD20-, CD25-, and B5-positive lymphocytes) and monocytes (CD14); phytohemagglutinin-, concanavalin A-, and pokeweed mitogen-induced and unstimulated proliferation of separated lymphocytes; unstimulated and pokeweed mitogen-stimulated production of IgG, IgM, or IgA; and serum interleukin-6, interleukin-1 beta, and serum C-reactive protein concentrations were measured preoperatively and on postoperative Days 1, 7, and 21. Significant changes were seen in these variables, but there were no differences between the groups. Three of the 12 patients in the allogeneic leukocyte-containing red blood transfusion group became human lymphocyte antigen (HLA) alloimmunized. No infections or other complications occurred in any patients. We conclude that HLA alloimmunization was the only effect that could be modified by use of autologous blood.
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PMID:Blood transfusion with autologous and leukocyte-depleted or standard allogeneic red blood cells and the immune response to open heart surgery. 794 71

We have previously shown that retinoids can induce differentiation of B cells in vitro as well as in vivo in patients with common variable immunodeficiency (CVI). While changes were observed over 1 week when retinoic acid (RA) was added to CVI hybridoma cells in vitro, maturation of the patients' B-cell compartment in vivo occurred only after 4 months of drug administration. We have now performed a 64-week open trial of oral 13-cis RA in five patients to see if prolonged treatment would result in continued improvement in their humoral immune compartment. In this trial, drug was given for 32 weeks followed by a 32-week wash-out period. During the treatment, the patients showed changes in a variety of parameters indicating an alteration towards normal of their humoral immune systems. This change included a fall in the elevated circulating interleukin-6 (IL-6) levels, a more normal display of B-cell surface markers (L-selectin and CD20), a decrease in B-cell size, and improved in vitro and in vivo B-cell function. In order to determine if VH gene use was affected by the retinoid treatment, VH gene expression in the CVI patients was characterized. Results showed an unusual predominance of non-mutated VH gene sequences, representative of cells that are recent bone marrow emigrants. While no common pattern of change occurred in VH gene segment use in the patients while on retinoid therapy, large-scale (> 10-fold) changes in the expression of these genes were observed in each individual over time. Taken together, these results provide multiple lines of evidence that 13-cis RA promotes maturation of B cells in patients with CVI. However, the effect appears to be partial, such that stimuli in addition to 13-cis RA will be necessary to provide for further B-cell differentiation in order to achieve normalization of humoral immunity.
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PMID:Long-term administration of 13-cis retinoic acid in common variable immunodeficiency: circulating interleukin-6 levels, B-cell surface molecule display, and in vitro and in vivo B-cell antibody production. 828 20

We have previously found that dimethyl sulfoxide (DMSO), a known inducer of differentiation in several kinds of myeloid cells, arrests proliferation of human lymphoid cells including Raji and Akata Burkitt's lymphoma cells at the G1 phase. We investigated whether DMSO affects cell proliferation and differentiation of the lymphoid cell line SKW6-CL4, which is capable of differentiating terminally into IgM-producing cells. As in the case of Raji, Akata, and Molt-4, the proliferation of SKW6-CL4 was reversibly arrested at the G1 phase by treatment with 2% DMSO for 5 days even in the presence of interleukin-6 (IL-6). DMSO inhibited spontaneous IgM secretion as well as IL-6-induced IgM production in SKW6-CL4 at a concentration lower than that affecting cell proliferation. Of the cell-surface differentiation markers CD10, CD20, CD21, and CD23, the expression of CD20 was suppressed by DMSO treatment, and partial restoration of the expression was observed 24 to 48 h after release from DMSO. The level of IL-6 receptor protein was not affected by DMSO treatment. These results indicate that DMSO not only arrests the cell cycle of a human lymphoid cell line SKW6-CL4 at the G1 phase but also inhibits the differentiation into IgM-secreting cells at a concentration lower than that affecting cell proliferation and that DMSO overcomes the effect of IL-6 on terminal differentiation of SKW6-CL4. As a whole, proliferation of human lymphoblastoid cell lines was revealed to be reversibly arrested at the G1 phase by DMSO, which is known to induce differentiation in several myeloid cells, without inducing cell differentiation.
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PMID:Reversible G1 arrest induced by dimethyl sulfoxide in human lymphoid cell lines: dimethyl sulfoxide inhibits IL-6-induced differentiation of SKW6-CL4 into IgM-secreting plasma cells. 854 66

Interleukin-6 (IL-6) is the major cytokine to date mediating antigen (Ag)- or mitogen-driven B cell differentiation. Recently, CD40 ligand (CD40L), with the co-stimulatory cytokines IL-4 and IL-10, has been shown to trigger immunoglobulin (Ig) secretion and class switching. In the present report, we have examined the role of IL-6 in mediating B cell differentiation and Ig secretion triggered with CD40L and/or these cytokines. Culture of splenic B cells with CD40L triggered (1) significant (5.4-fold) increases in IL-6 secretion; (2) differentiation, evidenced by sequential loss of B cell (CD20, CD21) and acquisition of plasma cell (CD38, PCA-1) surface antigens (Ags); and (3) Ig secretion. Interleukin-4 increased both IL-6 and IgG secretion stimulated by CD40L. Interleukin-10+ CD40L triggered 100-fold increments in IgG, IgA and IgM secretion, but IL-10 suppressed IL-6 secretion triggered with CD40L +/- IL-4. Exogenous IL-6 can further increase IgG secretion induced by CD40L + IL-10; moreover, the anti-IL-6 monoclonal antibody partially blocked IgG secretion triggered by CD40L +/- IL-4 or IL-10. Finally, IL-10 suppressed differentiation of B cells induced by CD40L. These studies suggest that CD40L augments Ig secretion in at least two mechanisms: by triggering IL-6 secretion and related differentiation, and by priming B cells for responsiveness to IL-10.
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PMID:CD40 ligand triggers interleukin-6 mediated B cell differentiation. 870 23

A 57-year-old female was admitted to Uji hospital for the further evaluation of nodular shadow on her right lung. During the period of admission, she developed cervical lymph node swelling. She was diagnosed as having malignant lymphoma (diffuse, small cleaved cell) by lymph node biopsy. She received combined chemotherapy and obtained partial remission for seven months until she developed fever and pancytopenia. Laboratory data showed increased number of large granular lymphocytes (LGLs) in blood. Bone marrow revealed increased number of LGLs with hemophagocytosis by macrophage. Surface marker analysis revealed LGLs were positive for CD2 CD16, and CD56 and negative for CD3, CD4, CD8, and CD20. T-cell receptor genes beta and gamma were in germ line configuration. Analysis of Epstein-Barr virus genome using termini probe indicated a monoclonal proliferation of LGLs. Reexamination of the biopsy specimen of lymph node revealed LGLs which was negative for CD3 and CD20. The patient was diagnosed as a leukemic phase of natural killer (NK) cell lymphoma complicated with hemophagocytic syndrome (HPS). Serum levels of interferon-gamma, macrophage colony-stimulating factor, granulocyte colony-stimulating factor, and interleukin-6 increased, which might be related to HPS.
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PMID:[Natural killer cell lymphoma having a nodular shadow in the lung as an initial finding, developed to leukemia complicated with hemophagocytic syndrome at the time of relapse]. 882 78

Interleukin-6 (IL-6) has in vitro demonstrated growth regulatory effects on tumor cells from patients with chronic lymphocytic leukemia (CLL) and lymphoma. The proliferation rate of these cells is usually very low and this is thought to be one of the reasons for the lack of a curative potential of cytostatic chemotherapy in CLL and low grade NHL. Recombinant human (rh) IL-6 might increase the in vivo proliferation rate leading to a higher sensitivity for chemotherapy. We tested this hypothesis by administering rhIL-6 to 9 CLL patients and 3 NHL patients in doses of 2.5 micrograms/kg, 5 micrograms/kg and 10 micrograms/kg s.c. daily for 5 days followed by CHOP chemotherapy on the last day of rhIL-6 injection. Six patients had two treatment cycles. The proportion of cells in S-phase was determined by the bromodeoxyuridine labeling index (LI). Three patients achieved a partial remission, one patient had progressive disease and the remaining patients demonstrated no change. Two patients, who received 10 micrograms/kg/day rhIL-6, demonstrated a significant increase in LI, one of these was first observed in the second treatment cycle. A significant decrease was seen in two patients receiving 2.5 micrograms/kg and 5 micrograms/kg respectively. Immunophenotypic assessment demonstrated that rhIL-6 increased the expression of CD20 in all CLL patients with a reversal after cessation of rhIL-6. We conclude that rhIL-6, in the dosage and schedule used in this study, did not increase the proportion of the cells in S-phase and that the growth stimulatory effects of rhIL-6 in CLL in vivo probably are insignificant. However, the role of rhIL-6 in CLL as inducer of increased CD20 expression prior to anti-CD20 antibody treatment remains to be determined.
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PMID:S-phase induction by interleukin-6 followed by chemotherapy in patients with chronic lymphocytic leukemia and non-Hodgkin's lymphoma. 1043 69

Eleven patients with relapsed fludarabine-resistant B-cell chronic lymphocytic leukemia (CLL) or leukemic variants of low-grade B-cell non-Hodgkin's lymphoma (NHL) were treated with the chimeric monoclonal anti-CD20 antibody rituximab (IDEC-C2B8). Peripheral lymphocyte counts at baseline varied from 0.2 to 294.3 x 10(9)/L. During the first rituximab infusion, patients with lymphocyte counts exceeding 50.0 x 10(9)/L experienced a severe cytokine-release syndrome. Ninety minutes after onset of the infusion, serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) peaked in all patients. Elevated cytokine levels during treatment were associated with clinical symptoms, including fever, chills, nausea, vomiting, hypotension, and dyspnea. Lymphocyte and platelet counts dropped to 50% to 75% of baseline values within 12 hours after the onset of the infusion. Simultaneously, there was a 5-fold to 10-fold increase of liver enzymes, d-dimers, and lactate dehydrogenase (LDH), as well as a prolongation of the prothrombin time. Frequency and severity of first-dose adverse events were dependent on the number of circulating tumor cells at baseline: patients with lymphocyte counts greater than 50.0 x 10(9)/L experienced significantly more adverse events of National Cancer Institute (NCI) grade III/IV toxicity than patients with less than 50.0 x 10(9)/L peripheral tumor cells (P = .0017). Due to massive side effects in the first patient treated with 375 mg/m(2) in 1 day, a fractionated dosing schedule was used in all subsequent patients with application of 50 mg rituximab on day 1, 150 mg on day 2, and the rest of the 375 mg/m(2) dose on day 3. While the patient with the leukemic variant of the mantle-cell NHL achieved a complete remission (9 months+) after treatment with 4 x 375 mg/m(2) rituximab, efficacy in patients with relapsed fludarabine-resistant B-CLL was poor: 1 partial remission, 7 cases of stable disease, and 1 progressive disease were observed in 9 evaluable patients with CLL. On the basis of these data, different infusion schedules and/or combination regimens with chemotherapeutic drugs to reduce tumor burden before treatment with rituximab will have to be evaluated.
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PMID:Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). 1049 91


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