International Journal of Cell Cloning, Vol 6, 241-261, Copyright © 1988 by AlphaMed Press
The suppressive effects of recombinant human tumor necrosis factor- alpha on normal and malignant myelopoiesis: synergism with interferon- gamma
F Herrmann, T Bambach, R Bonifer, A Lindemann, D Riedel, W Oster and R Mertelsmann
Department of Hematology, Johannes Gutenberg-University, Mainz, FRG.
The modulation of growth of normal and leukemic myeloid progenitor cells in
soft agar cultures by recombinant human tumor necrosis factor- alpha (TNF
alpha) and recombinant human interferon-gamma (IFN gamma) was investigated.
TNF alpha inhibited colony formation of all colony types representing
different maturational stages of normal progenitor cells committed to the
myeloid lineage with different orders of sensitivity. Blast-type colonies
derived from patients with acute myelogenous leukemia were more sensitive
to TNF alpha inhibition than progenitor cells purified from normal bone
marrow or bone marrow from patients with stable-phase chronic myelogenous
leukemia. The response of most colony types to IFN gamma was poor. However,
when IFN gamma was administered together with TNF alpha, synergistically
enhanced antiproliferative effects were detected in all colony types
tested. The antiproliferative action of IFN gamma on myelopoiesis was
enhanced in culture by the presence of autologous monocytes, presumedly by
inducing endogenous production of TNF alpha. However, TNF alpha seemed to
act directly on the progenitor cells themselves to suppress their clonal
growth, rather than involving accessory marrow elements such as monocytes
and/or T lymphocytes.
