Theophylline induces apoptosis of the IL-3 activated eosinophils of patients with bronchial asthma.
In bronchial asthma, eosinophils are upregulated and their survival is suggested to be prolonged by the action of some cytokines such as Interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF). We find here that the survival of eosinophils in the peripheral blood of patients with asthma is correlated with the serum levels of IL-3 but not of IL-5 and GM-CSF. Interestingly, theophylline is revealed to induce apoptosis of the prolonged survival eosinophils by IL-3, as judged by morphological changes and nucleosomal DNA fragmentation. During the apoptosis, caspase-3 in eosinophils stimulated by IL-3 is activated by theophylline. The substrate of caspase-3, poly (ADP-ribose) polymerase (PARP), is cleaved in the eosinophils after theophylline treatment. These results suggest that theophylline is able to induce apoptosis of the IL-3 activated eosinophils in patients with bronchial asthma, and that its clinical effectiveness may be due to the reduction of inflammatory cells in the airway.
Takeuchi
M
M
Second Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan.
Hayakawa
A
A
Takagi
K
K
Hiramatsu
K
K
Shimizu
Y
Y
Matsumoto
S
S
Hiramatsu
T
T
Ito
Y
Y
Kume
H
H
Suzuki
R
R
Yamaki
K
K