Modulation of Th1- and Th2-like cytokine production from mitogen-stimulated human peripheral blood mononuclear cells by phosphodiesterase inhibitors.
1. Effects of phosphodiesterase (PDE) inhibitors on the production of IFN-gamma, IL-2, IL-4 and IL-5 by phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) were investigated. In addition, we investigated the effects of dibutyrylcyclic AMP (dbcAMP) and a beta-adrenoceptor agonist on production of these cytokines. 2. Type IV, type III and nonselective PDE inhibitors were effective at inhibiting the production of IFN-gamma and IL-2 production in a dose-dependent manner. In contrast, IL-4 and IL-5 production was inhibited by only the highest concentration of type IV inhibitor, and other agents had no effect on the production. 3. Similarly, dbcAMP inhibited the production of IFN-gamma and IL-2 more potently than IL-4 and IL-5. 4. The addition of a beta-adrenoceptor agonist increased the inhibitory effect of PDE inhibitors tested on the production of IFN-gamma and IL-2. 5. These results indicate that PDE inhibitors or cAMP-elevating agents modulate Th1 cytokine more effectively than Th2 cytokine production.
Yoshimura
T
T
Pharmaceutical Division, Ogaki Municipal Hospital, Gifu, Japan.
Nagao
T
T
Nakao
T
T
Watanabe
S
S
Usami
E
E
Kobayashi
J
J
Yamazaki
F
F
Tanaka
H
H
Inagaki
N
N
Nagai
H
H
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis*; D007378:Interleukins / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D020105:Milrinone; D008934:Mitogens / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D020889:Rolipram; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D007378:Interleukins; D008934:Mitogens; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D011760:Pyrrolidinones; D003994:Bucladesine; D007371:Interferon-gamma; D013806:Theophylline; D020105:Milrinone; D020889:Rolipram