Inhibition of allergen-induced lung eosinophilia by type-III and combined type III- and IV-selective phosphodiesterase inhibitors in brown-Norway rats.
We examined the effect of a type IV (rolipram) and a combined type III and IV (Org 20421) isoenzyme-selective phosphodiesterase inhibitor upon allergen-induced pulmonary eosinophil recruitment in sensitised Brown Norway rats. Rats were sensitised with ovalbumin intraperitoneally and later challenged with ovalbumin aerosol which induced a significant increase in the total eosinophil and neutrophil count in bronchovalveolar lavage fluid at 24 hours (from 0.38 +/- 0.12 to 1.36 +/- 0.18 x 10(6), p < 0.01 and from 0.06 +/- 0.01 to 0.33 +/- 0.07 x 10(6), p < 0.01) respectively. Pretreatment with rolipram (30 mumol/kg) and Org 20421 (30 mumol/kg) abolished the eosinophilia and neutrophilia evoked by ovalbumin. We conclude that type IV and possibly type III isozyme phosphodiesterase inhibitors may regulate, directly or indirectly, eosinophil and neutrophil activity and/or those cells responsible for attracting them into the lung.
Elwood
W
W
Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Sun
J
J
Barnes
P J
PJ
Giembycz
M A
MA
Chung
K F
KF
D000280:Administration, Inhalation; D000336:Aerosols; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count / Q000187:drug effects; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects; D005260:Female; D007274:Injections, Intraperitoneal; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010047:Ovalbumin / Q000008:administration & dosage / Q000633:toxicity; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000188:drug therapy*; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011914:Rats, Inbred BN; D020889:Rolipram; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D000336:Aerosols; D000894:Anti-Inflammatory Agents, Non-Steroidal; C094013:ORG 20241; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D013844:Thiazoles; D010047:Ovalbumin; D020889:Rolipram