Comparison of anti-inflammatory mechanisms between doxofylline and theophylline in human monocytes.
Cytokines
Doxofylline
Methylxanthines
Monocytes
Superoxide anion
Theophylline
Journal
Pulmonary pharmacology & therapeutics
ISSN: 1522-9629
Titre abrégé: Pulm Pharmacol Ther
Pays: England
ID NLM: 9715279
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
01
05
2019
revised:
26
09
2019
accepted:
26
09
2019
pubmed:
30
9
2019
medline:
4
9
2020
entrez:
30
9
2019
Statut:
ppublish
Résumé
Methylxanthines are important pharmacological agents in the treatment of asthma and of chronic obstructive pulmonary diseases. The present study was designed to compare the ability of doxofylline and theophylline to modulate inflammatory pathways in human monocytes. Monocytes isolated from healthy anonymous human buffy coats were treated with doxofylline or theophylline in the presence of phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide (LPS), and their phenotype, the oxidative burst, cytokine expression and release, cAMP production, and protein kinase C (PKC) activity were evaluated. Doxofylline and theophylline did not have overlapping effects on human monocytes. While sharing some common characteristics, they differed significantly in their selectivity. Theophylline affected LPS- above PMA-induced cellular responsivity, while doxofylline behaved in the opposite manner. Furthermore, when testing PKC activity, we found an inhibitory effect of doxofylline but not of theophylline, at equimolar doses. In conclusion, our data support the growing hypothesis that doxofylline does not have a superimposable mechanism of action compared to theophylline, and this may both explain some differences in the risk/benefit ratio and may direct studies to tailor therapy for patients.
Sections du résumé
BACKGROUND
Methylxanthines are important pharmacological agents in the treatment of asthma and of chronic obstructive pulmonary diseases. The present study was designed to compare the ability of doxofylline and theophylline to modulate inflammatory pathways in human monocytes.
METHODS
Monocytes isolated from healthy anonymous human buffy coats were treated with doxofylline or theophylline in the presence of phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide (LPS), and their phenotype, the oxidative burst, cytokine expression and release, cAMP production, and protein kinase C (PKC) activity were evaluated.
RESULTS
Doxofylline and theophylline did not have overlapping effects on human monocytes. While sharing some common characteristics, they differed significantly in their selectivity. Theophylline affected LPS- above PMA-induced cellular responsivity, while doxofylline behaved in the opposite manner. Furthermore, when testing PKC activity, we found an inhibitory effect of doxofylline but not of theophylline, at equimolar doses.
CONCLUSIONS
In conclusion, our data support the growing hypothesis that doxofylline does not have a superimposable mechanism of action compared to theophylline, and this may both explain some differences in the risk/benefit ratio and may direct studies to tailor therapy for patients.
Identifiants
pubmed: 31563516
pii: S1094-5539(19)30115-4
doi: 10.1016/j.pupt.2019.101851
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Lipopolysaccharides
0
phorbolol myristate acetate
56937-68-9
Theophylline
C137DTR5RG
Protein Kinase C
EC 2.7.11.13
doxofylline
MPM23GMO7Z
Tetradecanoylphorbol Acetate
NI40JAQ945
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101851Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.