Selective Phosphodiesterase Type 4 Inhibitors Reduce the Prolonged Survival of Eosinophils Stimulated by Granulocyte-Macrophage Colony-Stimulating Factor

Masayuki Takeuchi; Yasuaki Tatsumi; Kiyoyuki Kitaichi; Kenji Baba; Ryujiro Suzuki; Eiji Shibata; Kenji Takagi; Ken-ichi Miyamoto; Takaaki Hasegawa; Kenzo Takagi

doi:10.1248/bpb.25.184

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Selective Phosphodiesterase Type 4 Inhibitors Reduce the Prolonged Survival of Eosinophils Stimulated by Granulocyte-Macrophage Colony-Stimulating Factor

Masayuki Takeuchi, Yasuaki Tatsumi, Kiyoyuki Kitaichi, Kenji Baba, Ryujiro Suzuki, Eiji Shibata, Kenji Takagi, Ken-ichi Miyamoto, Takaaki Hasegawa, Kenzo Takagi

Author information

Masayuki Takeuchi
Second Department of Internal Medicine and Laboratory Medicine, Nagoya University School of Medicine
Yasuaki Tatsumi
Department of Medical Technology, Nagoya University School of Health Sciences
Kiyoyuki Kitaichi
Department of Medical Technology, Nagoya University School of Health Sciences
Kenji Baba
Third Department of Medicine, Aichi Medical School, School of Medicine
Ryujiro Suzuki
Second Department of Internal Medicine and Laboratory Medicine, Nagoya University School of Medicine
Eiji Shibata
Department of Medical Technology, Nagoya University School of Health Sciences
Kenji Takagi
Department of Medical Technology, Nagoya University School of Health Sciences
Ken-ichi Miyamoto
Department of Hospital Pharmacy, Kanazawa University School of Medicine
Takaaki Hasegawa
Department of Medical Technology, Nagoya University School of Health Sciences
Kenzo Takagi
Department of Medical Technology, Nagoya University School of Health Sciences

Keywords: phosphodiesterase inhibitor, eosinophil survival, bronchial asthma, granulocyte-macrophage colony-stimulating factor, rolipram, XT-611

JOURNAL FREE ACCESS

2002 Volume 25 Issue 2 Pages 184-187

DOI https://doi.org/10.1248/bpb.25.184

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Abstract

It is well known that bronchial asthma is defined as chronic eosinophilic inflammation of the respiratory tract and that as one of the various types of inflammatory cells, eosinophils induce the airway inflammation of chronic asthma. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to play an important role in the prolongation of the survival of eosinophils. We investigated the inhibitory effect of the selective phosphodiesterase (PDE) 4 inhibitors, 3,4-dipropyl-4,5,7,8-tetrahydro-3H-imidazo[1,2-i]purin-5-one (XT-611) and rolipram, and the nonselective PDE inhibitor theophylline, against GM-CSF-induced prolongation of the survival of eosinophils isolated from patients with bronchial asthma. Eosinophils (10₆ cells/ml) were incubated in the presence of GM-CSF together with or without theophylline, rolipram or XT-611 at 37 °C, and the viable cells were assessed up to 4 d using Trypan blue dye exclusion. The presence of theophylline (10⁻⁴ M), rolipram (10⁻⁴—10⁻⁵ M) or XT-611 (10⁻⁴—10⁻⁵ M) significantly reduced the GM-CSF (10 pg/ml)-induced prolongation of viability of eosinophils. These findings suggest that selective PDE 4 inhibitors, including XT-611, may effectively reduce the activities of inflammatory cells in the airway of bronchial asthma patients.

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