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)

Genetic mechanisms leading to the development of multiple myeloma (MM) remain poorly understood. Given the frequency of chromosome 13 deletion in MM and the localization in 13q14 of the retinoblastoma susceptibility gene RB-1, an involvement of RB-1 in MM pathogenesis has been proposed. Moreover, interleukin-6 (IL-6) has been shown to be the main growth factor for MM in vitro and in vivo. The product of the RB-1 gene (pRB) can down-regulate IL-6 gene expression. Absence of pRB may then induce an autocrine IL-6 expression in myeloma cells and contribute to the autonomous growth of MM. As assessed in this review, heterozygous deletion of RB-1 is very common in MM but does not alter gene transcription and protein expression. Nevertheless, homozygous deletion of RB-1 has been identified in some MM patients with advanced disease and in the IL-6-autocrine human myeloma cell line U266. Thus, even if inactivation of RB-1 appears to be only a rare and late oncogenic event in MM and is not likely to represent the main mechanism involved in IL-6 up-regulation in MM, definitive assessment of the actual role played by RB-1 in MM pathogenesis still needs further investigation particularly the examination of pRB function.
Leuk Lymphoma 1997 Jan
PMID:The retinoblastoma susceptibility gene RB-1 in multiple myeloma. 915 53

Serum interleukin-6 (IL-6) levels were measured in 58 adult patients with newly diagnosed acute myelogenous leukemia (AML) using an ELISA method in order to find potential clinical correlations. Detectable average levels were 57 +/- 68 pg/ml and 52 patients (90%) had higher cytokine levels than normal donors. IL-6 levels (115 +/- 102 pg/ml versus 36 +/- 40 pg/ml, p = 0.0001) were higher in patients with fever of apparently non infectious origin, and higher levels were associated with higher percentage of blasts in the peripheral blood (R = 0.29, p = 0.04) and in the bone marrow (R = 0.39, p = 0.003), elevated serum LDH level (R = 0.36, p = 0.01), hyperbilirubinemia (R = 0.36, p = 0.008), elevated serum GGT level (R = 0.46, p = 0.003), and elevated serum GOT (R = 0.36, p = 0.008) and GPT levels (R = 0.44, p = 0.004). Highest IL-6 levels were observed in FAB M1 (86 +/- 112 pg/ml), M3 (73 +/- 69 pg/ml), and M6 (92 +/- 60 pg/ml) AML subtypes. Serum IL-6 levels in AML might be related to both non specific inflammatory reactions and the specific biology of the disease.
Leuk Lymphoma 1997 Jan
PMID:Serum interleukin-6 levels in adult acute myelogenous leukemia: relationship with disease characteristics and outcome. 915 58

Human immunodeficiency virus (HIV)-related body cavity-based lymphomas (BCBLs) are known to exhibit unusual clinical, immunophenotypic, and genotypic features, and have recently been found to harbor DNA sequences of a new human herpesvirus, designated Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8). The authors have encountered eight cases of HHV-8-associated BCBL in HIV-infected patients. A literature search revealed an additional 50 reported cases of HIV-related BCBL, as well as reports of several other disorders associated with HHV-8 DNA. Comprehensive analysis of the clinical and pathobiological features of all 58 known cases of HIV-related BCBL shows it to be a unique B-cell neoplasm with a strong propensity for body-cavity involvement without mass lesions and with little or no dissemination, poor prognosis, high grade usually immunoblastic morphology, late B-cell phenotype and genotype, no associated c-myc gene rearrangement, frequent presence of Epstein-Barr virus (EBV) genome, and uniform association with HHV-8 DNA. Considering these features in the context of other disorders associated with HHV-8 DNA, HHV-8 appears to play a causal role in BCBL, possibly in concert with EBV, and may induce this lymphoma through dysregulation of cytokines, particularly interleukin-6, or infection of an unusual B-cell subset. The characteristics of HHV-8-associated BCBL suggest a possible role for antiherpes or anticytokine agents in the treatment of this lymphoma.
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PMID:Human herpesvirus-8-associated body cavity-based lymphoma in human immunodeficiency virus-infected patients: a unique B-cell neoplasm. 922 48

We report a 53-year-old-man with an aggressive Ki-1 lymphoma who had high serum CA125, a marker protein of the epithelial ovarian cancer, and interleukin-6 (IL-6) concentrations. Both CA125 and IL-6 levels decreased after chemotherapy and elevated with disease progression. The patient's lymphoma cells obtained before chemotherapy grew continuously in vitro, were IL-6 dependent and were found to secrete CA125 in culture medium. These results indicate that CA125 can be secreted by Ki-1 lymphoma cells and IL-6 may promote the growth of Ki-1 lymphoma cells.
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PMID:High serum levels of CA125 and interleukin-6 in a patient with Ki-1 lymphoma. 926 49

Based on cDNA sequence data epsilon chain-specific antisense oligonucleotides were synthesized and checked on in vitro IgE production. Using peripheral blood cells from a hypereosinophilic patient and a human IgE myeloma cell line, U266, marked reduction of in vitro IgE production measured by PRIST was observed. The effect of epsilon antisenses proved to be isotype specific since IgG production by both peripheral blood cells and a lymphoma cell line, CESS, was not affected. Moreover, the expression of other markers on U266 (interleukin-6 receptor and gp130) were not influenced by epsilon-specific antisense oligonucleotides.
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PMID:Inhibition of IgE production by epsilon (epsilon) chain-specific antisense oligonucleotides (AOs) studied on human myeloma cell line U266 and peripheral blood mononuclear cells of a patient with hypereosinophilia. 929 1

We have recently demonstrated the presence of Kaposi's sarcoma-associated herpesvirus (KSHV) in cultured bone marrow (BM) stromal dendritic cells from all patients with myeloma studied. To show that these findings were not an artifact of tissue culture, we performed in situ hybridization (ISH) and polymerase chain reaction (PCR) to detect KSHV in BM core biopsies. Using ISH to open reading frame-72 (ORF 72), we localized KSHV to BM dendritic cells in 17 of 20 patients with myeloma, 2 patients with plasmacytosis associated with the acquired immunodeficiency syndrome, and 1 case of aplastic anemia. In contrast, BM from normal subjects (n = 4) and patients with lymphoma and leukemia (n = 21) did not contain KSHV. PCR amplification with KSHV primers demonstrated product in fresh BM biopsy samples from 6 of 7 myeloma patients, whereas three normal marrows contained no amplified product. These findings suggest that KSHV, possibly through alterations in the BM microenvironment and production of viral interleukin-6 (vIL-6), may stimulate and maintain abnormal plasma cell proliferation in myeloma and related disorders.
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PMID:Localization of Kaposi's sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma. 978 98

The understanding of the biology of multiple myeloma has advanced significantly in the past few years. The identification of the pivotal role of Interleukin-6 (IL-6), the soluble IL-6 receptor (sIL-6R), and how the ligand receptor complex interacts with the signal transducer gp130 has provided new biological insights into plasma cell disorders. Some studies have suggested that sIL-6R levels may have prognostic significance in MM, however this is not a consistent finding. Here the biology and function of IL-6 and sIL-6R are reviewed and the clinical significance of sIL-6R discussed.
Leuk Lymphoma 1997 Aug
PMID:Soluble IL-6R in plasma cell dyscrasias. 938 56

A case of Castleman's disease in a patient with type I neurofibromatosis and pheochromocytoma is reported. The association of pheochromocytoma and neurofibromatosis is well documented, but uncommon. Castleman's disease has not been previously documented in a patient with neurofibromatosis or pheochromocytoma and may represent a previously unrecognized association of this disease. Castleman's disease is an interleukin-6 (IL-6) mediated B-cell proliferation. We postulate a relationship between pheochromocytoma IL-6 secretion and Castleman's disease. The relevant literature relating to this unusual case is reviewed.
Leuk Lymphoma 1997 Nov
PMID:Castleman's disease in a 44-year-old male with neurofibromatosis and pheochromocytoma. 947 39

Seroepidemiology and polymerase chain reaction studies have strongly suggested that human herpesvirus type 8 (HHV-8) is associated with Kaposi's sarcoma, Castleman's disease, and body cavity-based lymphoma. The genome of HHV-8 harbors a viral analogue of the interleukin-6 (IL-6) gene. The amino acid sequence of the viral IL-6 (vIL-6) protein is 24.7% identical to human IL-6 (hIL-6). IL-6 as a B-cell growth and differentiation factor is known to play an essential role in the pathophysiology of B-cell tumors. Thus, it seems possible that virus-encoded IL-6 contributes to malignant growth of HHV-8-positive B-cell lymphatic tumors. We have tested a preparation of HHV-8-derived IL-6 for the ability to promote the proliferation of the human myeloma cell line INA-6, which is strictly dependent on exogenous IL-6 for growth and survival. Viral IL-6 significantly induced DNA synthesis of INA-6 cells, but required much more protein on a weight basis when compared with hIL-6 for maximal proliferation. The proliferative effect of vIL-6 was almost completely inhibited by a combination of anti-IL-6 receptor (IL-6R) and anti-gp130 antibodies or IL-6R superantagonist Sant7 and anti-gp130 antibodies. This report demonstrates that vIL-6 has proliferative activity on human cells and that the IL-6R and gp130 are involved in vIL-6 signaling in the myeloma cell line INA-6.
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PMID:Human herpesvirus type 8 interleukin-6 homologue is functionally active on human myeloma cells. 973 Oct 82

We report a 46-year-old man suffering from angiocentric lymphoma of the skin. On admission, he had atypical cells rich in basophilic granules in the bone marrow and peripheral blood, in addition to skin eruptions and bone marrow dysplasia. Immediately after diagnosis, the patient was treated with multidrug combination chemotherapy. At first, the chemotherapy markedly relieved the skin eruption and bone marrow dysplasia, and atypical cells in the bone marrow and peripheral blood disappeared rapidly. However, the disease gradually became resistant to chemotherapy, resulting in a gradual deterioration of the skin eruption and bone marrow dysplasia, and reappearance of atypical cells. The levels of serum cytokines such as interleukin-4 and interleukin-6, and of soluble interleukin-2 receptor correlated well with the disease states. These results suggest that the lymphoma cells directly or indirectly induce the production of these cytokines and that a dysregulated cytokine network, which might be caused by lymphoma cells, induces an increase in atypical cells.
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PMID:Bone marrow dysplasia with basophilic cells in a patient with angiocentric lymphoma. 955 59


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