Differential effect of phosphodiesterase inhibitors on IL-13 release from peripheral blood mononuclear cells.
Increased cyclic AMP (cAMP)-phosphodiesterase (PDE) activity in peripheral blood leucocytes is associated with the immunological inflammation that characterizes allergic diseases, such as atopic dermatitis and allergic rhinitis. Recently, it has been found that IL-13 has similar biological functions to IL-4. The aim of this study was to investigate the possible involvement of cAMP-PDE activity on IL-13 release from peripheral blood mononuclears cells (PBMC) from atopic asthma patients. Phytohaemagglutinin (PHA)-induced IL-13 release from PBMC was concentration-dependently inhibited by rolipram, a type 4 PDE inhibitor, as well as by dibutyryl cAMP, a membrane-permeant cAMP analogue. However, theophylline, a non-specific PDE inhibitor, and cilostazol, a type 3 PDE inhibitor, failed to inhibit IL-13 release. The inhibitory effect of rolipram was enhanced by the addition of forskolin (10(-4) m), an adenylyl cyclase stimulator. PHA itself did not alter the intracellular cAMP level. Rolipram concentration-dependently increased cAMP level in PHA-stimulated PBMC, and this increase was synergistically facilitated by the addition of forskolin (10(-4) m). These results suggest that type 4 PDE inhibitors, alone or synergistically in combination with forskolin, inhibit PHA-induced IL-13 release from PBMC of atopic asthma patients by elevating intracellular cAMP concentrations. These inhibitors have the potential to exert an anti-inflammatory effect by inhibiting IL-13 production in allergic diseases such as atopic asthma.
Yoshida
N
N
Second Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan.
Shimizu
Y
Y
Kitaichi
K
K
Hiramatsu
K
K
Takeuchi
M
M
Ito
Y
Y
Kume
H
H
Yamaki
K
K
Suzuki
R
R
Shibata
E
E
Hasegawa
T
T
Takagi
K
K
D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D000077407:Cilostazol; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D018793:Interleukin-13 / Q000096:biosynthesis*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D020889:Rolipram / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D018793:Interleukin-13; D010726:Phosphodiesterase Inhibitors; D010835:Phytohemagglutinins; D013777:Tetrazoles; D005576:Colforsin; D003907:Dexamethasone; D013806:Theophylline; D000242:Cyclic AMP; D020889:Rolipram; D000077407:Cilostazol