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)

Impaired hematopoiesis and dysregulated cytokine expression have important implications for cancer in the elderly. In aged people, hematopoiesis is dysregulated and becomes paradoxically down-modulated under periods of increased hematopoietic demand. This down-modulation may explain, at least in part, the increased incidence of anemia in the elderly, although the cause of anemia can usually be identified in these patients and frequently reversed with targeted therapy. An age-associated decrease in the expression of interleukin-2 may contribute to impaired cellular immunity. Additionally, the increased interleukin-6 production frequently found in the elderly may participate in promoting the survival and proliferation of malignant myeloma and in inducing resistance by myeloma cells to therapies that act through apoptosis. Dysregulation of the expression of these and other cytokines may be a mechanism contributing to age-related impairment of the hematopoietic response, the genesis and therapeutic resistance of specific malignancies, and cancer cachexia.
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PMID:Hematopoiesis and cytokines. Relevance to cancer and aging. 1068 71

In addition to signaling proliferation, growth factors may contribute to the persistence of hematopoietic tumors upon chemotherapeutical challenge. In multiple myeloma, malignant growth is mediated either by paracrine interleukin-6 (IL-6) elaborated by bone marrow stromal cells or via autocrine loops by malignant myeloma cells themselves. Although melphalan is one of the most active drugs in this tumor entity, the development of drug resistance frequently impedes cure of patients by attenuating melphalan-induced DNA-damage. We analyzed whether IL-6 protects XG-1 cells and plasma cells of a patient suffering from end-stage multiple myeloma (plasma cell leukemia) from melphalan with respect to DNA damage and DNA repair. Investigating the housekeeping gene glucose-6-phosphate dehydrogenase (G6PD) by using a PCR-stop assay, we found that there was more DNA damage in the G6PD gene of IL-6 deprived XG-1 and the patient's plasma cells, respectively, than in those with IL-6 supplementation. After cessation of melphalan exposure and 24 hours post-incubation in melphalan-free medium, DNA repair was observed in the patient's plasma cells but not in XG-1 cells. There was more DNA repair with IL-6 addition than without IL-6 addition. Similarly, the apoptotic cell fractions, as measured by flow cytometry, were lower if IL-6 was added to the medium. These results indicate that IL-6 may contribute to drug resistance in multiple myeloma.
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PMID:Interleukin-6 affects melphalan-induced DNA damage and repair in human multiple myeloma cells. 1201 94

In B cell development, interleukin-6 (IL-6) induces terminal maturation of B lymphocytes into antibody producing plasma cells. Terminal differentiated B cells cell cycle arrest and death follows. In contrast, IL-6 acts as a growth factor for malignant myeloma plasma cells and in some cases protects them from therapeutic treatment. In this study, we examined two cell lines that show different responses to IL-6. Lymphoblastoid CESS cells respond to IL-6 by terminally differentiating into antibody producing plasma cells, cell cycle arrest, and undergo cell death. Continuous addition of IL-6 to these cells induces transient activation of STAT3, SHP-2 phosphorylation, and does not alter bcl-X(L) and c-myc expression. In contrast, the myeloma line ANBL6 proliferates when stimulated with IL-6 and this correlates with prolonged STAT3 activation and up-regulation of bcl-X(L) and c-myc. Interestingly, gp130-associated SHP-2 phosphorylation was detected in the IL-6-induced CESS cells but not myeloma cell lines. The data show a very distinct IL-6 signal transduction and kinetics in these cell lines and the distinct molecular events correlate closely to the cell fate of the lymphoblast and myeloma cell lines.
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PMID:Distinct IL-6 signal transduction leads to growth arrest and death in B cells or growth promotion and cell survival in myeloma cells. 1204 Apr 51