Interleukin-6 inhibits apoptosis and tumour necrosis factor induced proliferation of B-chronic lymphocytic leukaemia
| Autor: | Panos Panayiotidis, Kwee Yong, A. V. Hoffbrand, Reittie Je |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Adult
DNA Replication Male Cancer Research medicine.medical_treatment Apoptosis DNA Fragmentation Biology law.invention Immunophenotyping law hemic and lymphatic diseases medicine Humans Aged Neoplasm Staging Aged 80 and over B-Lymphocytes DNA synthesis Cell growth Interleukin-6 Tumor Necrosis Factor-alpha Antibodies Monoclonal Hematology DNA Neoplasm Middle Aged Molecular biology Leukemia Lymphocytic Chronic B-Cell Growth Inhibitors Recombinant Proteins Neoplasm Proteins Cytokine Oncology Cell culture Recombinant DNA Neoplastic Stem Cells DNA fragmentation Tumor necrosis factor alpha Female Cell Division |
| Zdroj: | Leukemialymphoma. 22(1-2) |
| ISSN: | 1042-8194 |
| Popis: | There is now good evidence that tumour necrosis factor [TNF] stimulates DNA synthesis of B-chronic lymphocytic leukaemia (B-CLL) cells. The malignant clone produces TNF, and addition of exogenous TNF up-regulates the TNF mRNA in B-CLL cells. Interleukin-6 (rIL-6) may also be important in this growth loop. We studied the interaction of TNF and IL-6 in the regulation of DNA synthesis (3H-TdR uptake), cytokine release and cell survival in CLL cells in vitro. Addition of TNF (100 U/ml over 5 days) enhanced DNA synthesis from 718 +/- 284 (mean cpm +/- SE) to 2730 +/- 545 compared to cells cultured in medium alone (n = 16, p < 0.01). TNF-alpha induced DNA synthesis was inhibited in all cases studied by the addition of anti-TNF monoclonal antibody (5 micrograms/ml) to cell cultures. Spontaneous IL-6 protein release was enhanced in the presence of TNF (100 U/ml and 250 U/ml) by CLL cells at 48 hours of culture 143.6% and 172% (p < 0.05, n = 6). At 120 hours of culture, the increase was 323% and 412.5% (4 of 7 cases) of the control respectively. IL-6 (100 U/ml or greater) increased spontaneous DNA synthesis (3H-TdR uptake) but, in the presence of high concentrations of TNF-alpha, inhibited TNF induced DNA synthesis in a dose dependent manner. Cell survival was reduced in the presence of anti-IL-6 mAb, while IL-6 was able to protect CLL cells from spontaneous apoptosis. These results suggest that IL-6 in an autocrine manner may inhibit DNA synthesis but prolongs survival in CLL cells. Increased serum IL-6 levels were detected in 27 of 50 cases of CLL, the mean level being significantly higher in Rai Stage III and IV cases compared to Rai Stage O-II cases. |
| Databáze: | OpenAIRE |
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