Differential expression of eicosanoid pathways after whole blood stimulation in asthma patients
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Elsevier
Abstract
Objectives: Asthma is a heterogeneous disease regarding its pathophysiology, clinical symptoms,
and response to treatment. Eicosanoids are important inflammatory mediators, able to
either promote or attenuate the underlying chronic airway inflammation.We compared eicosanoid
expression patterns in the blood circulation and in stimulated blood leukocytes of asthma patients
to identify differences in eicosanoid release which may be related to airway inflammation.
Methods: Blood was collected from 198 adult asthmatic patients and 63 healthy controls, participating
in the German Center for Lung Research (DZL) ALLIANCE cohort. Eicosanoid release from
leukocytes was analyzed using heparinized whole blood after in vitro stimulation with zymosan.
Additionally, circulating eicosanoids were measured directly from ethylenediaminetetraacetic acid
(EDTA) plasma. Eicosanoids were extracted via solid phase extraction and quantified by highperformance-
liquid-chromatography-tandem-mass-spectrometry (HPLC-MS2).
Results: Eicosanoid levels were low in blood circulation with no significant differences between
asthmatics and controls, except for leukotriene E4 (LTE4)which was slightly elevated in asthmatics. After
in vitro stimulation we observed an inhibition of prostaglandin and thromboxane biosynthesis only in
patientswith severe asthmawhich was related to the regular use of systemic corticosteroids. In contrast,
a significant increase was shown for formation of the 5-Lipoxygenase (5-LOX) product LTE4 in steroidnaïve
asthmatics with moderate as well as severe disease severity but not in subjects with systemic
steroid treatment. Furthermore 15-Hydorxyeicosatetraenoic acid (15-HETE) productionwas elevated in
asthmatic patients with mild-to-moderate disease activity but dropped down in severe asthmatics.
Conclusions: Profiling of eicosanoid production in stimulatedwhole blood samples showeda specific
biosynthesis pattern of asthmatic patients, which is influenced by the use of systemic corticosteroids.
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