Effects of the phosphodiestrase-4 inhibitor rolipram on lung resistance and inflammatory reaction in experimental asthma.
The aim of this study was to evaluate the influence of pretreatment with the phosphodiesterase-4 inhibitor rolipram on pulmonary resistance, influx of inflammatory cells, and histamine concentration in bronchoalveolar lavage fluid (BALF) during an experimental asthmatic reaction induced in ovalbumin (OA)-sensitized guinea pigs, challenged with OA inhalation. The experiment was performed in three groups of guinea pigs: two experimental groups, pretreated with rolipram or dexamethasone, and a control group without any pretreatment. Lung resistance (LR) was continuously recorded under suppression of spontaneous breathing during early asthmatic reaction. BALF was obtained before and at three time points up to 24 hr after the challenge. In the untreated, control animals a transient, significant increase in neutrophils, total and CD4+ lymphocytes, macrophages, eosinophils, and in histamine concentration in BALF was noted. Pretreatment with rolipram significantly reduced LR, eosinophils infiltration, and histamine release into the bronchoalveolar space during the early asthmatic reaction. These effects were generally comparable with those of dexamethasone, except that dexamethasone also reduced the influx of neutrophils into BALF.
Nejman-Gryz
P
P
Department of Internal Diseases, Pneumology and Allergology, Warsaw Medical University, Warsaw, Poland.
Grubek-Jaworska
H
H
Glapiński
J
J
Hoser
G
G
Chazan
R
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003907:Dexamethasone / Q000627:therapeutic use*; D006168:Guinea Pigs; D006632:Histamine / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D008297:Male; D010047:Ovalbumin; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D020889:Rolipram / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D003907:Dexamethasone; D006632:Histamine; D010047:Ovalbumin; D020889:Rolipram