Interleukin-4 inhibits both paracrine and autocrine tumor necrosis factor-alpha-induced proliferation of B chronic lymphocytic leukemia cells.
The proliferative response of purified malignant B cells from 26 patients with chronic lymphocytic leukemia (CLL) was investigated in vitro. In the majority of these patients, a proliferative response could be induced by the combination of tumor necrosis factor (TNF)-alpha and PMA. The concentration of PMA was found to be critical and showed a sharp optimum. In most cases maximal proliferation was obtained with as little as 0.1 ng/mL PMA. In all cases tested, TNF-alpha- induced proliferation could be inhibited completely by the addition of low doses of interleukin-4 (IL-4). Maximal inhibition was already found with 400 pg/mL IL-4. Inhibition by IL-4 was not caused by a downmodulation of TNF receptors. Apart from TNF-alpha, IL-2 was also in synergy with PMA able to induce proliferation in B-CLL cells of some patients. This IL-2- induced proliferation could be inhibited both by IL-4 and by neutralizing anti-TNF-alpha antibodies. This shows that TNF-alpha also can act as an autocrine growth factor. These data indicate that TNF-alpha is an important growth factor for neoplastic B-CLL cells and that IL-4 provides a tool to interfere with this TNF-alpha response.[1]References
- Interleukin-4 inhibits both paracrine and autocrine tumor necrosis factor-alpha-induced proliferation of B chronic lymphocytic leukemia cells. van Kooten, C., Rensink, I., Aarden, L., van Oers, R. Blood (1992) [Pubmed]
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