Effects of several glucocorticosteroids and PDE4 inhibitors on increases in total lung eosinophil peroxidase (EPO) levels following either systemic or intratracheal administration in sephadex- or ovalbumin-induced inflammatory models.
Representative glucocorticosteroids (GCS) and phosphodiesterase IV (PDE4) inhibitors were compared in several models of pulmonary inflammation ranging in severity. Lung tissue eosinophil peroxidase (EPO) levels rather than bronchoalveolar lavage fluid (BALF) EPO or eosinophil percentages were used to indicate eosinophil recruitment after intratracheal instillation of sephadex beads in rats or nebulized ovalbumin in sensitized guinea pigs. A single oral or intratracheal administration of a GCS was effective against mild and robust sephadex-induced eosinophilia whereas the PDE4 inhibitors evaluated appeared more effective in the milder sephadex models. The GCS were also more effective against sephadex-induced than ovalbumin-induced eosinophilia. The effectiveness of the GCS and PDE4 inhibitors improved when the severity of the ovalbumin-induced eosinophilia was decreased. Multiple day dosing also improved activity. These studies indicated that activity was influenced greatly by administration protocols, the severity of the inflammatory response and possibly the method used for estimating eosinophil recruitment.
Hammerbeck
D M
DM
3M Pharmaceuticals, 3M Company, St. Paul, Minnesota 55144, USA.
McGurran
S M
SM
Radziszewski
P L
PL
Egging
E A
EA
Johnson
D D
DD
Hupperts
A M
AM
Gullikson
G W
GW
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000201:enzymology; D001507:Beclomethasone / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D019819:Budesonide / Q000494:pharmacology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003907:Dexamethasone / Q000494:pharmacology; D003911:Dextrans; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000187:drug effects* / Q000201:enzymology*; D000068298:Fluticasone; D005938:Glucocorticoids / Q000494:pharmacology*; D006168:Guinea Pigs; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology*; D008168:Lung / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D010047:Ovalbumin; D010544:Peroxidases / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology
D000730:Androstadienes; D001549:Benzamides; D003911:Dextrans; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D011725:Pyridines; C102660:CDP 840; D019819:Budesonide; D003907:Dexamethasone; D010047:Ovalbumin; C025614:sephadex; D000068298:Fluticasone; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram; D001507:Beclomethasone; C087566:piclamilast