In vitro production of granulocyte-macrophage colony-stimulating factor in
aplastic anemia: possible mechanisms of action of antithymocyte globulin
SD Nimer, DW Golde, K Kwan, K Lee, S Clark and R Champlin
Department of Medicine, UCLA School of Medicine 90024-1678.
Various abnormalities of lymphokine production have been described in
patients with aplastic anemia. To determine if abnormal production of
hematopoietic growth factors could contribute to the process of aplastic
anemia we studied the in vitro production of human granulocyte- macrophage
colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) by
phytohemagglutinin (PHA)- and antithymocyte globulin (ATG)- stimulated
peripheral blood lymphocytes from 29 patients with aplastic anemia and 15
normal controls. GM-CSF production in response to 1% PHA was seen in nearly
all samples (43 of 44) and similar amounts of GM-CSF were produced by
patients with aplastic anemia and normal controls. Production of GM-CSF by
ATG-stimulated lymphocytes was seen in 7 of 23 patients with aplastic
anemia (30%); two of these patients also demonstrated low-level spontaneous
production of GM-CSF. Production of GM-CSF in response to ATG was also seen
in 2 of 11 normal controls (18%) and barely detectable spontaneous
production of GM-CSF was seen in both. Biologically active IL-3 could also
be detected in PHA- or ATG- stimulated peripheral blood mononuclear cells
in several patients and normal controls. Our results indicate that
lymphocytes from patients with aplastic anemia can be stimulated in vitro
to produce normal quantities of GM-CSF, suggesting that impaired potential
for production of T-cell derived hematopoietic growth factors is unlikely
to account for the marrow hypoplasia seen. In several patients
overproduction of GM-CSF was observed, consistent with the notion that some
patients with aplastic anemia may have circulating activated T cells. We
also demonstrate that ATG can stimulate the production of growth factors
such as IL-3 and GM-CSF, supporting the role for ATG in stimulating
hematopoiesis.
Volume 78,
Issue 1,
pp. 163-168,
07/01/1991
Copyright © 1991 by The American Society of Hematology
