In vivo production of interleukin-5, granulocyte-macrophage colony-
stimulating factor, macrophages colony-stimulating factor, and
interleukin-6 during intravenous administration of high-dose interleukin-2
in cancer patients [see comments]
MR Schaafsma, JH Falkenburg, JE Landegent, N Duinkerken, S Osanto, P Ralph, K Kaushansky, G Wagemaker, J Van Damme and R Willemze
Department of Hematology, University Medical Center, Leiden, The
Netherlands.
Recombinant human interleukin-2 (IL-2), administered to cancer patients by
continuous intravenous (IV) infusion (3 x 10(6) U/m2/d), was found to
induce the in vivo production of colony-stimulating factors (CSF). Plasma
obtained from patients during IL-2 treatment stimulated in vitro colony
formation of normal human bone marrow cells, depleted of mononuclear
phagocytes and T lymphocytes. This colony-stimulating activity (CSA) was
identified as IL-5, granulocyte-macrophage CSF (GM- CSF), and macrophage
CSF (M-CSF), by the ability of specific antibodies against these factors to
neutralize their effects. The presence of IL-2- induced GM-CSF and M-CSF
was also demonstrated by specific radioimmunoassays. During IL-2 treatment,
plasma also contained detectable levels of IL-6, which was measured in a
bioassay. Using a cDNA-polymerase chain reaction (PCR) with specific primer
sets for the various CSF, we showed that IL-2 treatment induced the
expression of mRNA for M-CSF, GM-CSF, IL-3, and IL-5, but not for
granulocyte CSF (G- CSF) in peripheral blood mononuclear cells, suggesting
differential expression of CSF in vivo in response to IL-2. Furthermore, no
negative regulators of hematopoiesis, such as interferon gamma (IFN-gamma)
or tumor necrosis factor-alpha (TNF-alpha), were found in plasma. These
data illustrate that in vivo administration of high-dose IL-2 may result in
a stimulatory effect on hematopoiesis. The induction of detectable levels
of IL-5 and GM-CSF in the circulation may explain the eosinophilia and
neutrophilia observed in these patients.
Volume 78,
Issue 8,
pp. 1981-1987,
10/15/1991
Copyright © 1991 by The American Society of Hematology