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C Denzlinger, A Kapp, M Grimberg, HH Gerhartz and W Wilmanns
Medizinische Klinik III, Ludwig-Maximilians Universitat, Munich, West
Germany.
The hematopoietic cytokine granulocyte-macrophage colony-stimulating factor
(GM-CSF) is being used in clinical trials for its potential in the
treatment of hematopoietic insufficiency due to various causes. Involvement
of leukotrienes in the effects of GM-CSF is suggested by analytical and
pharmacologic evidence obtained in vitro. However, until now no data in
support of a role of leukotrienes in GM-CSF action in vivo have been
presented. In the present investigation this question was approached by
measurement of endogenous cysteinyl leukotriene formation in patients
treated with the cytokine for cytopenia induced by cytostatic drugs or for
refractory anemia with excess of blasts (RAEB). Endogenous cysteinyl
leukotriene formation was assessed by determination of urinary leukotriene
metabolites using combined high- performance liquid chromatography and
radioimmunoassay analysis. After GM-CSF administration a distinct increase
in urinary cysteinyl leukotrienes was found in the cytopenic and the RAEB
patients that ranged from 2.3- to 57-fold and 2.4- to 333-fold,
respectively. In the cytopenic patients the increase in leukotriene
production was correlated to an expansion of peripheral blood leukocytes;
RAEB patients responded to GM-CSF with enhanced leukotriene biosynthesis
even if the peripheral leukocytes decreased, possibly due to an abnormal
number and/or irritability of leukotriene-producing cells. The increase in
endogenous leukotriene production during therapy with GM- CSF may indicate
that leukotrienes play a role in GM-CSF action in vivo.
This article has been cited by other articles:
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| Copyright © 1990 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
