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Production of cytokines by bone marrow cells obtained from patients with
multiple myeloma
A Lichtenstein, J Berenson, D Norman, MP Chang and A Carlile
Department of Medicine, VA Wadsworth-UCLA Medical Center, Los Angeles, CA
90073.
Previous work with continuously cultured multiple myeloma lines suggested
that cytokine production by tumor cells may mediate some of the medical
complications of this disease. To further investigate this issue, we
assayed freshly obtained bone marrow (BM) cells from myeloma patients for
the in vitro production of cytokines and the presence of cytokine RNA.
Production of cytokine protein was assessed by bioassays with the aid of
specific neutralizing anticytokine antibodies. These assays detected
interleukin-1 (IL-1) and tumor necrosis factor (TNF) secretion by myeloma
BM cells, which was significantly greater than secretion from similarly
processed BM cells of control individuals. In contrast, lymphotoxin and
interleukin-2 (IL-2) production could not be detected. The levels of IL-1
and TNF produced in vitro peaked at 24 hours of culture and correlated with
stage and the presence (or absence) of extensive osteolytic bone disease.
Northern blot analysis demonstrated the presence of IL-1 beta and TNF RNA
in uncultured myeloma BM cells but no detectable IL-1 alpha or lymphotoxin
RNA. In addition, the amount of cytokine RNA correlated with protein
production, being significantly greater in patients' BM cells than in
control marrow. These data suggest a role for IL-1 beta and/or TNF in the
pathophysiology of multiple myeloma and argue against a role for
lymphotoxin or IL-2.
Volume 74,
Issue 4,
pp. 1266-1273,
09/01/1989
Copyright © 1989 by The American Society of Hematology
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