Phosphodiesterase type 4 inhibitor rolipram inhibits activation of monocytes during extracorporeal circulation.
OBJECTIVE
Cardiopulmonary bypass is associated with systemic inflammatory response syndrome and risk of multiorgan injury mediated by activated leukocytes. Phosphodiesterase type 4 is the predominant phosphodiesterase isozyme in leukocytes and plays a key role in the regulation of leukocyte activation. The aim of this study was to examine the effect of rolipram, a selective phosphodiesterase type 4 inhibitor, on functional changes of monocytes during simulated extracorporeal circulation.


RESULTS
Simulated extracorporeal circulation was established by recirculating heparinized human blood for 120 minutes on a membrane oxygenator with or without 10 micromol/L of rolipram. L-selectin and CD11b expression of monocytes were measured with flow cytometry. C4d fragment, Bb fragment, C5b-9, and interleukin-6 were measured with enzyme immunoassay. Rolipram reduced the increase in CD11b expression and the decrease in L-selectin expression of monocytes in response to simulated extracorporeal circulation. Rolipram inhibited the increase in C4d fragment and interleukin-6, but it did not affect the increase in Bb fragment or C5b-9.


CONCLUSIONS
Rolipram inhibited changes in adhesion molecule expression and interleukin-6 release by activated monocytes in simulated extracorporeal circulation. This study suggests that phosphodiesterase type 4 inhibition could be feasible therapeutic strategy to prevent exaggerated inflammatory response and organ injury in patients undergoing cardiopulmonary bypass.
Sato
Yukio
Y
Division of Thoracic Surgery, Jichi Medical School, Tochigi, Japan. tcvysato@jichi.ac.jp
Hiramatsu
Yuji
Y
Homma
Satoshi
S
Sato
Makiko
M
Sato
Shyoko
S
Endo
Shunsuke
S
Sohara
Yasunori
Y
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000328:Adult; D039481:CD11b Antigen / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D003167:Complement Activation / Q000276:immunology; D015935:Complement C4b / Q000276:immunology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005112:Extracorporeal Circulation; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D019041:L-Selectin / Q000276:immunology; D008297:Male; D008955:Models, Cardiovascular; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D010107:Oxygenators, Membrane; D010446:Peptide Fragments / Q000276:immunology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D020889:Rolipram / Q000494:pharmacology*
D039481:CD11b Antigen; D015815:Cell Adhesion Molecules; D015850:Interleukin-6; D010446:Peptide Fragments; D010726:Phosphodiesterase Inhibitors; D019041:L-Selectin; D015935:Complement C4b; C032261:complement C4d; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram