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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines are regulatory molecules that are produced by a variety of cell types and are characterized by numerous biologic functions involved in the regulation of the immune system and hematopoiesis. This review summarizes the functions and regulation of cytokines in lymphomas and discusses the effect of a specific cytokine, interleukin-6 (IL-6), in B-cell lymphomas. IL-6 is a multipotent cytokine that can mediate the differentiation of B-cells into immunoglobulin-secreting cells, stimulate the autocrine or paracrine growth of myeloma cells, induce acute-phase proteins in liver cells, and may influence the pathogenesis of several diseases by autocrine or paracrine mechanisms. Patients with non-Hodgkin's lymphoma (NHL) have increased serum concentrations of IL-6; increased IL-6 levels can be associated with the presence of B-symptoms. Data presented in this review indicate that neoplastic cells from patients with NHL contained high concentrations of IL-6. Thus, elevated serum levels of IL-6 appear to originate from the lymphoma cells in patients with B-cell NHL, suggesting that the neoplastic cells may modulate the general status of patients with B-cell NHL. The inhibition or modification of the production of IL-6 in lymphoma cells may lead to a more effective control of the general status of patients with B-cell NHL.
Leuk Lymphoma 1998 Mar
PMID:Production and effects of interleukin-6 and other cytokines in patients with non-Hodgkin's lymphoma. 963 77

Interleukin-6 (IL-6) is the major growth factor for the malignant plasma cell clone in patients with multiple myeloma (MM). Although interferon-alpha (IFN-alpha) has been widely used as maintenance therapy in MM, controversy exists as to its clinical utility. This review summarizes data showing that cell growth arrest brought about by type I (IFNs-alpha/beta) and type II (IFN-gamma) IFNs occurs in part through utilization/modification of various components of the otherwise stimulatory Jak-STAT and Ras signaling pathways triggered by IL-6. Recent experimental results indicating that IFN-alpha acts as a survival factor for certain myeloma cell lines and frequently induces endogenous IL-6 expression may help to explain the conflicting clinical findings obtained in this heterogeneous disease with this usually potent growth inhibitor. By comparison, consistent antiproliferative activity exhibited by IFN-gamma on IL-6-dependent myeloma cell lines and primary myeloma cells from patients suggests that further investigation of the possible value of this cytokine in the treatment of MM may be warranted.
Leuk Lymphoma 1998 May
PMID:Growth control mechanisms in multiple myeloma. 964 60

Pyoderma gangrenosum is a neutrophilic dermatosis that is frequently associated with malignancies such as myeloproliferative disorders. The development of this dermatologic disorder is thought to be mediated by immunological mechanisms. A case of pyoderma gangrenosum associated with the administration of alpha2b-interferon (alpha2b-IFN) in a patient with chronic granulocytic leukemia is described. Discontinuation of alpha2b-IFN and the administration of cyclosporin A and prednisone resulted in cure of the pyoderma gangrenosum. Serum levels of tumor necrosis factor, interleukin-6 and soluble interleukin-2 receptor increased when the cutaneous lesions appeared and returned to normal levels when the lesion healed. We believe that this is the first reported case of pyoderma gangrenosum associated with alpha2b-IFN therapy.
Leuk Lymphoma 1998 Jun
PMID:Pyoderma gangrenosum triggered by alpha2b-interferon in a patient with chronic granulocytic leukemia. 966 91

Interleukin-6 (IL-6) is a potent immunomodulatory cytokine that may have pathogenetic and prognostic significance in a number of disorders. The objective of this study was to examine the correlation between serum IL-6 levels and phenotypic characteristics, as well as failure-free survival of patients with low-grade non-Hodgkin's lymphomas (NHL). Using a sensitive enzyme-linked immunoabsorbent assay (ELISA), we measured IL-6 in frozen sera from 55 healthy controls and in the pre-treatment frozen sera from 100 low-grade lymphoma patients who were enrolled on protocols at MD Anderson Cancer Center. Serum IL-6 levels were correlated with clinical and laboratory features at diagnosis and with failure-free survival. The serum IL-6 levels were > or =2 pg/mL in 9% (median, <0.91 pg/mL; range, <0.91-4.31 pg/mL) of controls versus 25% of the indolent lymphoma patients (median, <0.91 pg/mL; range <0.91 to 225.97) (p = 0.0118). Serum IL-6 levels were higher in patients with B-symptoms (p = 0.02), an elevated P2-microglobulin level (> or =3.0 mg/L) (p = 0.00013), and unfavorable International Index (p = 0.03). Patients with elevated serum IL-6 levels had an inferior failure-free survival (log rank p = 0.008) compared with those with normal serum IL-6 levels (three-year-failure-free-survival = 55% versus 81%, respectively). In conclusion a minority (25%) of patients with indolent non-Hodgkin's lymphomas have elevated serum levels of IL-6 at diagnosis. In these individuals, high IL-6 levels are associated with adverse disease features, and predictive of a shorter failure-free survival.
Leuk Lymphoma 1998 Aug
PMID:High serum interleukin-6 levels correlate with a shorter failure-free survival in indolent lymphoma. 971 18

Uteroglobin (UG) is a steroid-inducible, multifunctional, secreted protein with antiinflammatory and antichemotactic properties. Recently, we have reported a high affinity UG-binding protein (putative receptor), on several cell types, with an apparent molecular mass of 190 kDa (Kundu, G. C., Mantile, G., Miele, L., Cordella-Miele, E., and Mukherjee, A. B. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 2915-2919). Since UG is a homodimer in which the 70 amino acid subunits are connected by two disulfide bonds, we sought to determine whether UG monomers also interact with the 190-kDa UG-binding protein and if so, whether it has the same biological activity as the dimer. Surprisingly, we discovered that in addition to the 190-kDa species, another protein, with an apparent molecular mass of 49 kDa, binds reduced UG with high affinity and specificity. Both 49- and 190-kDa proteins are readily detectable on nontransformed NIH 3T3 and some murine cancer cells (e. g. mastocytoma, sarcoma, and lymphoma), while lacking on others (e.g. fibrosarcoma). Most interestingly, pretreatment of the cells, which express the binding proteins, with reduced UG dramatically suppresses extracellular matrix (ECM) invasion, when such treatment had no effect on fibrosarcoma cells that lack the UG-binding proteins. Tissue-specific expression studies confirmed that while both 190- and 49-kDa UG-binding proteins are present in bovine heart, spleen, and the liver, only the 190-kDa protein is detectable in the trachea and in the lung. Neither the 190-kDa nor the 49-kDa protein was detectable in the aorta. Purification of these binding proteins from bovine spleen by UG-affinity chromatography and analysis by SDS-polyacrylamide gel electrophoresis followed by silver staining identified two protein bands with apparent molecular masses of 40 and 180 kDa, respectively. Treatment of the NIH 3T3 cells with specific cytokines (i.e. interleukin-6) and other agonists (i.e. lipopolysaccharide) caused a substantially increased level of 125I-UG binding but the same cells, when treated with platelet-derived growth factor, tumor necrosis factor-alpha, interferon-gamma, and phorbol 12-myristate 13-acetate, did not alter the UG binding. Taken together, these findings raise the possibility that UG, through its binding proteins, plays critical roles in the regulation of cellular motility and ECM invasion.
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PMID:Uteroglobin (UG) suppresses extracellular matrix invasion by normal and cancer cells that express the high affinity UG-binding proteins. 971 16

Primary effusion lymphoma (PEL; also known as body cavity-based lymphoma) is recognized as a new and unique lymphoma entity occurring predominantly, but not exclusively in human immunodeficiency virus (HIV)-seropositive patients with acquired immunodeficiency syndrome (AIDS). PEL grows exclusively in body cavities as serous lymphomatous effusion without evidence of mass disease or dissemination. Their most unique feature is infection with the newly discovered human herpesvirus-8 (HHV-8; also known as Kaposi's sarcoma-associated herpesvirus), often accompanied by co-infection with Epstein-Barr virus (EBV). A number of continuous lymphoma cell lines have been established from the malignant pleural effusion, ascitic fluid and peripheral blood of patients with AIDS- and non-AIDS-associated PEL. While all cell lines are HHV-8+, about half of them also contain EBV sequences. Stimulation of the cell lines causes switch from latent to lytic HHV-8 infection. The cells are generally negative for T and B cell immunomarkers (except for CD138 suggesting a pre- or terminal plasma cell stage) and positive for some activation and adhesion markers; they are genotypically B cells with their immunoglobulin genes rearranged. Complex, hyperdiploid karyotypes with multiple structural abnormalities are seen in the cell lines examined. No alterations of known proto-oncogenes are detected in PEL, with the exception of BCL-6 mutations occurring in a large percentage of cases. Heterotransplantation of the cell lines into immunodeficient mice leads to the development of lymphomatous effusion and marked angiogenesis. As HHV-8 contains DNA sequences of several protein homologues, the cell lines express various cytokines, cytokine receptors, chemokines, cell cycle and anti-apoptosis modulators which are upregulated upon stimulation. Indeed, some cell lines produce high levels of (human) interleukin-6 and interleukin-10. Taken together, these cell lines represent very important model systems for the elucidation of the pathobiology of PEL; furthermore, the cell lines are extremely useful scientific tools providing a resource to pursue studies of HHV-8-mediated pathogenic mechanisms.
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PMID:Lymphoma cell lines: in vitro models for the study of HHV-8+ primary effusion lymphomas (body cavity-based lymphomas). 976 92

ESb lymphoma cells injected i.v. into DBA/2 (H-2d) mice multiply rapidly in the liver and kill all mice in a few days. Adoptive transfer of allogeneic C57B1/6 (H-2b) tumor-immune or normal splenic lymphocytes to sublethally irradiated DBA/2 mice induced a marked antitumor state, graft-versus-leukemia (GVL), increasing the mean survival time 2-3-fold, but also induced an acute and lethal graft-versus host disease (GVHD). We have undertaken experiments to try to dissociate GVL from GVHD. Transfer of immune spleen cells induced a greater GVL than transfer of normal spleen cells with an equivalent to GVHD. Three to five million immune or normal CD8+ T lymphocytes were sufficient to induce both GVL and GVHD. Individual DBA/2 mice were labeled and followed. In mice undergoing GVHD, the spleens were repopulated by donor (H-2b) lymphocytes, and tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were present in the sera of 26 of 27 and 18 of 20 mice, respectively, together with increased amounts of TNF-alpha and IL-6 mRNA in their spleens. This was in contrast to DBA/2 mice receiving allogeneic cells but not developing GVHD. Both interferon-alpha/beta (IFN-alpha/beta) and IL-12, which had proven very effective in association with adoptive transfer of syngeneic immune T lymphocytes in inhibiting ESb metastases, enhanced GVHD when administered with allogeneic immune or normal spleen cells, and >90% of mice died. Intensive IL-2 treatment inhibited GVHD while maintaining GVL.
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PMID:Role of cytokines in GVL (ESb lymphoma) and GVHD after adoptive transfer of allogeneic T lymphocytes in mice. 978 5

Sixty six patients with non-Hodgkin's lymphomas (NHL) were studied, interleukin-6 (IL-6) was revealed in the blood sera of 33 patients. IL-6 was revealed more frequently in patients with high-grade malignant (p < 0.05) than in those with low-grade malignancy. The largest group of IL-6 positive patients included NHL patients with diffuse large B-cell lymphoma and angioimmunoblastic lymphoma. The marked relationship was found between the serum IL-6 levels and the stage of disease: the serum IL-6 level was significantly lower in untreated patients with Stages II and III disease than in those with end-stage (IV) NHL. IL-6 significantly decreased upon remission, comparable with its level before the initiation of treatment. Analysing the association of prognosis of disease with the serum IL-6 showed that in the group of patients with good (The SNLG index < 2) and intermediate (2 < SNLG index < by 2.6) prognosis, the concentration of this cytokine was significantly lower than in those with poor prognosis (SNLG index > 2.6). There was a significant decrease of the total survival rates of NHL with serum IL-6 found. Therefore, IL-6 is a good prognostic marker in NHL and associated with the activity of a malignant process. Additionally, the increased serum IL-6 levels correlated with NK activities positively and with serum IL-4 levels negatively.
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PMID:[Diagnostic and prognostic value of interleukin-6 in malignant non-Hodgkin's lymphomas]. 984 10

An 88-year-old woman was admitted with generalized lymphadenopathy, anemia, and thrombocytopenia. On admission, a peripheral blood examination showed a red blood cell count of 146 x 10(6)/microliter, a hemoglobin concentration of 6.9 g/dl, and a platelet count of 5.0 x 10(4)/microliter. Blood examination detected polyclonal hypergammaglobulinemia; the results of the direct/indirect Coombs' test were positive; and an elevated cold agglutinin titer and high platelet associated IgG (PA-IgG) level indicated the existence of autoantibodies. Serum cytokine measurements disclosed an elevated level of interleukin-6 (IL-6). Immunoblastic lymphadenopathy-like T cell lymphoma was diagnosed on the basis of lymph node biopsy specimens. VP-16 and steroid therapy alleviated the patient's lymphadenopathy, anemia, thrombocytopenia, and hypergammaglobulinemia. These findings suggest that tumor cells with a T cell phenotype produced IL-6 in large quantities, thus provoking B-cell and plasmacytic histologic changes and humoral disease manifestations, including hypergammaglobulinemia.
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PMID:[Immunoblastic lymphadenopathy-like T cell lymphoma with high levels of serum interleukin-6, cold agglutinin disease, and immune thrombocytopenia]. 986 23

Interleukin-6 plays a central role in normal B-cell maturation and in proliferation of some B-cell malignancies including multiple myeloma and some non Hodgkin's lymphomas (NHL). Furthermore, this cytokine also plays a major role in acute phase response by mediating synthesis of acute phase proteins such as C-reactive protein (CRP). In order to evaluate the exact role of CRP serum level as a simple prognostic factor, we analyzed CRP and IL-6 serum levels in 39 patients with NHL. Eleven patients had low grade NHL, 15 intermediate grade NHL, and 13 high grade NHL. Thirty percent of the patients presented detectable IL-6 serum levels (mean+/-SD: 33.6+/-95.2 U/ml, range: 0 to 500). Increased serum CRP levels were found in 42% of the patients with a mean of 29.2+/-41.97 mg/l] (range: 0 to 129). Thirty seven patients were studied for both markers. Three groups of patients were determined. One with low IL-6 and CRP serum levels (N=21), a second with high level of both markers (N=10), and the third with high serum CRP levels alone (N = 5). Only one patient had high level of serum IL-6 with no detectable CRP. The correlation of serum IL-6 and CRP levels with patient survival was investigated. Median survival in the group with low IL-6 level was not reached. 67% of patients of this group were still alive at 32 months from diagnosis. The group of patients with detectable IL-6 had a median of survival of 12 months (p<0.025). The survival of patients with a CRP<10 mg/l was not reached. 75% of patients survive at 32 months from diagnosis, whereas the group with higher CRP level reached a median survival at 8.5 months (p<0.009). As expected, on univariate analysis, there is a significant relationship between CRP and IL-6 levels (p<0.00017), and CRP levels and B symptoms (p<0.001). Furthermore there is a significant relationship between CRP and LDH levels (p<0.042).These results indicated that CRP may be considered as a valuable and easy prognostic biomarker of NHL.
Leuk Lymphoma 1998 Oct
PMID:C-reactive protein serum level is a valuable and simple prognostic marker in non Hodgkin's lymphoma. 986 99


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