Interleukin-4 inhibits both paracrine and autocrine tumor necrosis
factor-alpha-induced proliferation of B chronic lymphocytic leukemia cells
C van Kooten, I Rensink, L Aarden and R van Oers
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service,
Amsterdam.
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.
Volume 80,
Issue 5,
pp. 1299-1306,
09/01/1992
Copyright © 1992 by The American Society of Hematology
