The effect of rolipram, a type IV phosphodiesterase inhibitor, on Pseudomonas aeruginosa infection of respiratory mucosa.
We have investigated the effect of rolipram, a type IV phosphodiesterase inhibitor, on Pseudomonas aeruginosa infection of the respiratory mucosa of an organ culture model and on the reduction in intracellular cAMP levels seen in human nasal epithelial cells incubated with P. aeruginosa culture filtrate. We have compared rolipram with salmeterol, a long-acting beta-2 agonist, and have also studied the effect of the two agents together. Infected organ cultures had significantly (P < or = .05) increased epithelial damage. Rolipram significantly (P < or = .05) reduced P. aeruginosa-induced epithelial damage and reduced the total number of bacteria adhering to the respiratory mucosa (P < or = .04) in a concentration-dependent manner, although neither rolipram nor salmeterol affected P. aeruginosa growth in broth cultures. Rolipram reduced P. aeruginosa-induced mucosal damage more than salmeterol (P < or = .03). The effect of the two agents was neither additive nor synergistic. Rolipram, salmeterol and both agents together significantly (P < or = .01) increased intracellular cAMP levels in epithelial cells treated with P. aeruginosa culture filtrate. Rolipram alone increased cAMP more than salmeterol or both agents together (P < or = .01), probably because of an interaction between the two agents. These results suggest that agents that elevate intracellular cAMP protect the epithelium during bacterial infection. Rolipram is more effective than salmeterol in preventing P. aeruginosa-induced epithelial damage.
Dowling
R B
RB
Host Defence Unit, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, United Kingdom.
Johnson
M
M
Cole
P J
PJ
Wilson
R
R
D001422:Bacterial Adhesion; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000032:analysis; D006801:Humans; D008855:Microscopy, Electron, Scanning; D009297:Nasal Mucosa / Q000187:drug effects / Q000382:microbiology* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D011760:Pyrrolidinones / Q000494:pharmacology*; D020889:Rolipram
D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D000242:Cyclic AMP; D020889:Rolipram; D002118:Calcium